Gut Microbiome–Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders
- Janet M. Sasso
Janet M. SassoCAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United StatesMore by Janet M. Sasso
- ,
- Ramy M. Ammar
Ramy M. AmmarBayer Consumer Health, R&D Digestive Health, Darmstadt 64295, GermanyMore by Ramy M. Ammar
- ,
- Rumiana Tenchov
Rumiana TenchovCAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United StatesMore by Rumiana Tenchov
- ,
- Steven Lemmel
Steven LemmelCAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United StatesMore by Steven Lemmel
- ,
- Olaf Kelber
Olaf KelberBayer Consumer Health, R&D Digestive Health, Darmstadt 64295, GermanyMore by Olaf Kelber
- ,
- Malte Grieswelle
Malte GrieswelleBayer Consumer Health, R&D Digestive Health, Darmstadt 64295, GermanyMore by Malte Grieswelle
- , and
- Qiongqiong Angela Zhou*
Qiongqiong Angela Zhou*Email: [email protected]CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United StatesMore by Qiongqiong Angela Zhou
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Abstract
Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that the gut and brain are in constant bidirectional communication, of which gut microbiota and its metabolic production are a major component, and form the so-called gut microbiome–brain axis. Disturbances of microbiota homeostasis caused by imbalance in their functional composition and metabolic activities, known as dysbiosis, cause dysregulation of these pathways and trigger changes in the blood–brain barrier permeability, thereby causing pathological malfunctions, including neurological and functional gastrointestinal disorders. In turn, the brain can affect the structure and function of gut microbiota through the autonomic nervous system by regulating gut motility, intestinal transit and secretion, and gut permeability. Here, we examine data from the CAS Content Collection, the largest collection of published scientific information, and analyze the publication landscape of recent research. We review the advances in knowledge related to the human gut microbiome, its complexity and functionality, its communication with the central nervous system, and the effect of the gut microbiome–brain axis on mental and gut health. We discuss correlations between gut microbiota composition and various diseases, specifically gastrointestinal and mental disorders. We also explore gut microbiota metabolites with regard to their impact on the brain and gut function and associated diseases. Finally, we assess clinical applications of gut-microbiota-related substances and metabolites with their development pipelines. We hope this review can serve as a useful resource in understanding the current knowledge on this emerging field in an effort to further solving of the remaining challenges and fulfilling its potential.
This publication is licensed under
CC-BY 4.0.
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Attribution (BY): Credit must be given to the creator.
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License Summary*
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License Summary*
You are free to share (copy and redistribute) this article in any medium or format and to adapt (remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
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Introduction
ARTICLE SECTIONS
The Earth microbiome represents the majority of the planet’s biodiversity. Microbial life was the first to inhabit Earth. (1) Microbes regulate global nutrient cycles, greenhouse gas exchange, as well as disease transmission and protection, thus providing essential life support to the planet. (2) Among many other harbors, including plants, animals, soil, and entire ecosystems, a wide diversity of microorganisms colonize the human body, which are now known to play an essential role in the human host by regulating key physiological functions.
The large collection of microorganisms inhabiting the human body are predominantly bacteria, but also viruses, protozoa, fungi, and archaea. They are collectively known as the human microbiota. Those microorganisms residing in the digestive tracts are known as gut flora or gut microbiota. As a matter of fact, there are more bacterial cells in the human body than human cells─roughly 40 trillion bacterial cells versus only 30 trillion human cells. Together, they function as an extra organ in the human body─a so-called “forgotten organ”─since these microbes have a collective metabolic activity equal to a virtual organ. (3) The collective genome of the gut microbes, the gut microbiome, exceeds over 100 times the amount of human genome in the body. (4) Considering such enormous genetic potential of the microbiota, it is anticipated that it plays a role in virtually all physiological processes in the human body, including metabolic functions and immune homeostasis. (5−11)
Despite being considered a relatively new field of research, the first reports of human-associated microbiota date back to the 17th century when Antonie van Leeuwenhoek described five different kinds of oral bacteria. (12) In the following decades, the foundations of microbiology were laid, and knowledge of the host–microorganism interactions has accumulated (Figure 1). (13−22) Despite these early findings, rapid development of the field only started when methods to culture anaerobic organisms were set up in the mid-20th century when representatives of the microbiota were grown and studied in the laboratory. (23)
Figure 1
Figure 1. Timeline of major research and development milestones related to the microbiome. (12−30,39,49−80)
In the 2010s, the gut microbiome field burst into the life sciences research and industry, which prompted Forbes to declare the 2010s “The Decade of the Microbiome.” (24) This growth in the field was largely related to the National Institutes of Health’s “The Human Microbiome Project” (25) and the MetaHIT project funded by the European Union. (26) In 2005, the International Human Microbiome Consortium (IHMC) was founded in a cooperative effort to study the microbiome in human health and disease with the ultimate goal of applying this knowledge to prevent and/or treat diseases, and the abovementioned megaprojects have contributed to fulfilling this goal. They provided significant evidence for the relationship between metabolic, neurological, and autoimmune disorders; allergies, infections, and cancers; and the microorganisms that live on and in humans. Specifically, gastrointestinal diseases/disorders, such as inflammatory bowel diseases that include both Crohn’s disease and ulcerative colitis, irritable bowel syndrome (IBS), functional dyspepsia (FD), constipation, celiac disease, and more, are attracting attention with their close relation to the gut microbiome. Because of these findings and the essential part the gut microbiome plays in drug metabolism, the microbiome has become a popular target in the biotechnology industry. In 2010, the first extensive catalogue of human intestinal microbial genes was published on the basis of the studies of 124 individuals. (27) In 2011, the Human Microbiome Project published the sequences of 178 bacterial species. (28)
Although DNA sequencing has been used for decades, it was only after the development of next-generation sequencing when metagenomic studies became affordable. (29) The term metagenomics is used to describe genetic studies of microbial assemblies from environmental samples using sequence-based bioinformatics tools. (30) The goal of these studies is to identify the taxonomic diversity of the microbiota and to differentiate the biological roles of the representatives of such samples by performing functional metagenomics.
The human microbiota plays an essential role in human physiology and pathology. It collaborates closely with the digestive tract in several important aspects: (a) it promotes digestion by assisting the absorption of nutrients by gut cells or the fermentation of some food fractions, which generate important metabolites, including short-chain fatty acids; (31) (b) it supports the maturation of the digestive tract by participating in the assembly of gastrointestinal mucus and promoting the enzymatic activity of the mucosa; (32) (c) it performs a barrier function against pathogens and toxins, where some bacteria release antimicrobial agents that protect from the pathogenic bacteria; (33) (d) it plays a protective role in promoting the immune system development; and (e) it supports in the synthesis of essential vitamins like vitamin B: Magnúsdóttir et al. estimated that 86% of the recommended daily allowance (RDA) of vitamin B6, 37% of the RDA of vitamin B9, 31% of the RDA of vitamin B12, and 27% of the RDA of vitamin B3 could be provided by the human gut microbiota. (34)
Gut microbial disruption (dysbiosis) causes not only gastrointestinal disorders but also disorders in other distal organs and systems. Not long ago, it was found that gut bacteria can affect the central nervous system (CNS) functions. (35−38) Indeed, the gut and brain are in constant bidirectional communication, of which the microbiota and its metabolic production are a major component. The gut and brain connect via a neuro-immuno-humoral network of signaling pathways known as the gut microbiome–brain axis, which includes the vagus nerve, the immune system, the hormonal system, and bacterial metabolites and products. (39) The digestive system, including the inhabiting microbiota, was even called “the second brain” (40) at the time when scientists were beginning to realize that the gut and the brain in humans were involved in constant crosstalk and significantly modulate each other’s function. During disturbance of the microbiota homeostasis caused by an imbalance in their functional composition and metabolic activities, known as dysbiosis, these routes are dysregulated and cause changes in the permeability of the blood–brain barrier (BBB), neuroinflammation, and other pathological malfunctions, including a range of neurodevelopmental and neurodegenerative disorders. (41) Disorders of the gut–brain interaction (DGBI) is the recent term proposed by Rome Foundation guidelines for a range of functional gastrointestinal disorders including but not limited to IBS, FD, and functional constipation. This highlights the central role of the miscommunication between the gut and brain in these digestive disorders. (42) The gut microorganisms transform and metabolize dietary- and host-derived substances to generate a diverse set of metabolites with important local and systemic outcomes, thereby building a network of immunological, neuronal, and endocrine signaling pathways.
It is generally believed that bacterial colonization begins during birth. (43) The neonatal microbiota differs depending on mode of delivery: in vaginally delivered infants, it resembles the maternal vaginal microbiota, while the microbiota in those delivered by cesarean section resembles the maternal skin microbiota. (44) Premature birth, feeding method, and perinatal administration of antibiotics are also among the conditions affecting the development of the neonatal microbiome. (45) Recently, a new mode of horizontal mother-to-infant microbiome transmission has been revealed where microbes in the maternal gut shared genes with microbes in the infant gut during the perinatal period, which starts shortly before birth and prolongs throughout the first few weeks after birth. (46) A major factor of gut microbiota composition during adulthood is diet. Prompt changes in microbiota composition take place in response to dietary style changes. Specific patterns have been reported in plant-based versus animal-based diets. (47,48) The development and modifications of the gut microbiota are influenced by multiple other factors, such as exposure to stress, environmental conditions, medications intake, lifecycle, medical disorders, and procedures.
The human gut microbiota is divided into many groups called phyla. The gut microbiota primarily comprises four main phyla, including Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, with the Firmicutes and Bacteroidetes representing 90% of gut microbiota. (81,82) The majority of bacteria reside within the gastrointestinal tract, with most predominantly anaerobic bacteria housed in the large intestine. (83)
In recent years, sizable technological progress and wealth of knowledge have promoted the advancement of microbiome research, thereby enhancing our understanding of its relationship to human physiology and pathologies. In this paper, we review the advances in the knowledge related to the human gut microbiome, its complexity and functionality, its communication with the central nervous system, and the effect of the gut microbiome–brain axis on mental and digestive health. We examine data from the CAS Content Collection, (15) the largest human-curated collection of published scientific information and analyze the publication landscape of recent research in order to provide insights into the scientific advances in the area. We also discuss the correlations between the gut microbiota composition and various diseases, specifically digestive system diseases, mental, and neurodegenerative disorders. We furthermore explore the gut microbiota metabolites with regard to their impact on brain, digestive functions, and their associated diseases. Subsequently, we assess the clinical applications of gut microbiota-related substances and metabolites, their development pipelines, disease categories, development stages, and publication trends. We hope this review can serve as a useful resource in understanding the current state of knowledge in the field of gut microbes and the gut microbiome–brain interactions in an effort to further solve the remaining challenges for fulfilling the potential of the field.
Landscape of Gut Microbiome Research─Insights from the CAS Content Collection
ARTICLE SECTIONS
The CAS Content Collection (84) is the largest human-curated collection of published scientific knowledge. It is a comprehensive resource to access and remain well-informed on the world’s available scientific literature across disciplines, including chemistry, biomedical sciences, engineering, materials science, agricultural science, and many more, thus allowing quantitative analysis of global scientific publications against variables, such as time, research area, application, disease association, and chemical composition. A search in the CAS Content Collection showed an intense increase of the documents related to microbiome research in the past decade, which overcame other “omics” exploration─for example, the number of proteomics-related documents held up after the initial burst in the early 2000s and were surpassed by the microbiome documents after 2016 (Figure 2, inset). Currently, there are over 250 000 scientific publications (mainly journal articles and patents) in the CAS Content Collection related to gut/intestinal microbiome/microbiota. Nearly 15 000 of them are related to various aspects of mental and gut health. There is a steady, exponential growth of the number of journal articles over time that has been rather explosive from 2021–2022 (Figure 2). The number of patents rapidly grew until 2004, which possibly correlated with the initial accumulation of knowledge and its transfer into patentable applications. Later on, the growth substantially slowed down, perhaps awaiting the forthcoming breakthroughs in the gut microbiome awareness (Figure 2).
Figure 2
Figure 2. Journal and patent publication trends on gut microbiome research related to mental and gut health according to the CAS Content Collection. Inset: microbiome vs proteome document yearly trends.
The United States, China, Japan, and Korea are the leaders in the number of published journal articles (Figure 3A) and patents (Figure 3B) related to gut microbiome research in the areas of mental and gut health.
Figure 3
Figure 3. Top countries publishing journal articles (A) and patents (B) related to gut microbiome research in mental and gut health.
Figure 4 presents the flow of patent filings from different applicant locations to various patent offices. Because patent protection is territorial, and the same invention may be filed for protection in multiple jurisdictions, we looked at all relevant filings on gut microbiome research in mental and gut health. One patent family may have been counted multiple times when it was applied in multiple patent offices. There are diverse patent filing strategies: some patent assignees, such as those from China and Korea, file foremost in their home country patent offices (CN, KR), with a smaller proportion filing through other patent offices or other jurisdictions. Others, for instance United States-based applicants, have a nearly equal number of US and WO filings and a considerable number of filings at other patent offices, such as the European Patent Office (EP) and Canada (CA).
Figure 4
Figure 4. Flow of patent filings related to gut microbiome research in mental and gut health from different patent assignee locations (left) to various patent offices of filing (right). The abbreviations on the right indicate the patent offices of United States (US), Australia (AU), World Intellectual Property Organization (WO), Canada (CA), Austria (AT), European Patent Office (EP), Israel (IL), Norway (NO), Hong Kong (HK), Mexico (MX), Japan (JP), Brazil (BR), Spain (ES), India (IN), Russian Federation (RU), China (CN), and Korea (KR).
In order to better understand the advance in this research area, we examined the occurrence and trends of certain key concepts in the scientific publications relevant to the gut microbiome research in mental and gut health (Figure 5). With respect to the cumulative number of publications, “immunity” and “gut microbiome” appear as top concepts in the area (Figure 5A), thereby reflecting the rising interest in the relationship between the gut microbiome and systemic immune response pathways and the critical role the gut microbiome plays in training and development of the host’s innate and adaptive immune system. It is noteworthy that the concept concerning the gut–brain relationship exhibits the greatest growth rate in the past two years (Figure 5B), thereby characterizing it as the trendiest concept in the field.
Figure 5
Figure 5. Key concepts in the scientific publications relevant to the gut microbiome research in mental and gut health. (A) Number of publications exploring key concepts related to gut microbiome research in mental and gut health. (B) Trends in key concepts presented in the articles related to gut microbiome research in mental and gut health during the years 2016–2021. Percentages are calculated with yearly publication numbers for each key concept, normalized by the total number of publications for the same concept in the same time period.
Gut-Microbiota-Participant Bacteria
ARTICLE SECTIONS
The human gut microbiome, as mentioned above, is a complex mixture of microorganisms, including viruses, archaea, bacteria, yeasts, and fungi, interacting with each other and with their host in complex ways. These interactions at various times involve symbiosis, mutualism, antagonism, and even predation. Not only does the gut microbiome interact directly with the gastrointestinal (GI) tract, but it also interacts with the immune system that is present in the GI tract and with the neurological system through various signaling systems. Gastrointestinal signaling is mediated in part by microbial metabolites and is involved in regulating the gut–brain axis in the host. (85) This section focuses on the bacterial microbiome by first discussing the techniques used to identify and study the gut microbiome. Then, we will discuss the human GI tract from an ecological viewpoint. The phyla commonly found in the gut microbiome will be defined and discussed. Finally, we will focus on probiotics and related compositions (prebiotics, postbiotics, synbiotics, and psychobiotics) and present recent examples of each class to illustrate the current state of the art.
Techniques Used to Study the Gut Microbiome
Until recently, about 400 bacterial species were identified in the human microbiome using conventional culturing techniques. (86) These techniques, by their nature, underestimate the actual number of species because, to culture a bacterium successfully, one needs to provide the correct nutrients, pH, and redox environment to enable growth. Conventional culture techniques favor fast-growing and nonfastidious species over those present in low concentration, which requires unusual culture conditions and/or complex nutritional requirements. (86) Most isolation methods use selective agents, such as bile salts, to enrich the numbers of a desired bacterial type over others in the sample. The choice of the proper selective agent then becomes important. Some gut bacteria depend on other microorganisms in the gut to provide the nutrients they require for growth “cross-feeding.” Devising culture media for these can be a hit-or-miss proposition. Some bacteria will only grow in niches that have a narrow range of pH and/or redox potential, which may be difficult to maintain in vitro. Although there have been methodological advances in anaerobic culturing techniques, they tend to be tedious, time-consuming, and require specialized equipment. (31) The successful culture of strict anaerobic bacteria requires training, experience, and careful planning. Additionally, some bacteria might be alive but unculturable. Intercellular adherence may reduce the number of organisms that can give rise to colonies. (87)
The development of culture-independent metagenomic approaches, such as 16S RNA gene sequencing and high-throughput sequencing, have been an enabling factor in the study of the human gut microbiome. This topic was reviewed in depth by Sankar et al. in 2015. (86) The 16S rRNA gene exhibits several advantages, including its distribution in all bacterial species, its absence in eukaryotes, its stability over time, and its size (∼1500 bp), that make it suitable for bioinformatic analyses. High-throughput sequencing methods have given unprecedented access to the analysis of the microbial diversity of complex microbiotas, particularly through metagenomic approaches. Two strategies used are high-throughput sequencing of pooled PCR-amplified 16S rRNA and shotgun sequencing of all DNA fragments present, which enables identification of the microorganisms present and their metabolic genes. With these molecular techniques, it is now estimated that the human GI microbiota comprises more than 2000 species using modern molecular methods. (86,88)
Recent impressive advances in next generation sequencing technologies, along with the progress and innovations of metagenomics, metabolomics, multiomics, bioinformatics, and artificial intelligence tools, have provided prospects to better characterize the microbial populations and their functions and help in better correlation prediction.
Gastrointestinal Tract
The gut microbiome varies according to the GI anatomy, which varies in terms of physiology, pH and O2 tension, flow rates (rapid from the mouth to the cecum, slower afterward), substrate availability, and host secretions. (89) Figure 6 presents a representation of the GI tract with some of the bacterial taxa present. The GI tract consists of the stomach, duodenum, jejunum, ilium, cecum, and colon, with each environment ascending in pH and growing progressively more anaerobic from stomach to colon. Each section of the GI tract presents a unique ecological niche that exerts selective pressure on the microbiome. It is an open system with nutrients entering the system intermittently and wastes also leaving intermittently. The microbiome is affected by many factors, including diet, medications (especially antibiotics), ethnicity, age, and general health. (82,83)
Figure 6
Figure 6. Gut-microbiota-participant bacteria.
The stomach is an extreme habitat because it is highly acidic (pH = ∼1.5). Once, it was considered sterile because of its acidity until the discovery of Helicobacter pylori in this hostile environment in 1982. The microbial population in the gastric environment is low and in the range of 101–103 cells/mL. (87) Investigations since this discovery have revealed that the gastric fluid is predominated by the members of Firmicutes, Bacteroidetes, and Actinobacteria. (87) The gastric mucosa was found to have a rich diversity with bacterial members belonging to Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, and Actinobacteria. In healthy human stomach, the genera Streptococcus, Prevotella, Veillonella, Rothia, and Haemophilus were found to be predominant; however, the composition of the gastric microbiota is dynamic and affected by such factors as diet, drugs, and diseases. (90)
The small intestine comprises the duodenum, jejunum, and ileum. The duodenum has a pH of 5–6.8. Bacterial numbers are 103–104 cells/mL where Firmicutes predominate. (91) The jejunum and ileum have a higher pH (6–8) with a 104–108 cell/mL density that comprises strict to facultative anaerobic Gram-positive and Gram-negative bacteria. The small intestine is lined with simple columnar epithelial tissue, which is covered by a mucus layer, and has a large surface area because of the villi and microvilli. When food enters the duodenum, the pH and bacterial load are low. These small intestinal mucosae are associated with members of phyla Bacteroidetes and Firmicutes. Food is blended with bile, bicarbonate, and digestive enzymes in the duodenum, and when the intestinal contents reach the large intestine, the food blend has been converted to a neutral to alkaline pH. The small intestine provides a more challenging environment for microbial colonizers given the short transit times (3–5 h) and the high bile concentrations. (83,91)
The large intestine consists of the cecum and colon and is characterized by slow flow rates and pH varying from 6 to 7.8. It harbors by far the largest microbial community. The large intestine is strictly anaerobic, and the cell density reaches 1012 cells/mL. The large intestine is home to the most complex bacterial diversity in the GI tract because of several factors, such as its larger volume, moderate or less acidic pH, low concentration of bile salts, and the longer retention time caused by slower peristalsis. Five major phyla─Firmicutes, Bacteroidetes, Actinobacteria, Verrucomicrobia, and Proteobacteria─covering a wide range of bacterial genera─Clostridium, Fusobacterium, Bacteroidetes, Actinomyces, and Propionibacterium─are associated with the large intestine. Other Gram-positive cocci─Micrococci, Peptococci, Peptostreptococci, and Ruminococci─have been also reported to play crucial roles in the large intestine. Food that has not been degraded in the upper GI tract reaches the large intestines and supports the microbiota with nutrients and energy. The carbohydrates present are fermented to carbon dioxide, hydrogen, methane, and short-chain fatty acids (SCFA) (primarily acetate, propionate, and butyrate). Most of the SCFA produced in the large intestine are absorbed by the host and provide an energy source. The amount of energy derived from SCFA accounts for 6–9% of the total energy requirement. (82,88,91,92)
The microbiome composition of the intestinal lumen, known as mucosal and epithelial spaces of the GI tract, is highly diverse and comprises Verrucomicrobia, Fusobacteria, Asteroplasma, Cyanobacteria, Actinobacteria, Lentisphaera, Spirochaetes, Bacteroidetes, Proteobacteria, Bacilli, Clostridia, and Mollicutes. The predominating genera are Escherichia, Klebsiella, Enterococcus, Bacteroides, Ruminococcus, Dorea, Clostridium, Coprococcus, Weisella, and Lactobacillus. Other genera found include Granulicatella, Streptococcus, and Veillonella. (83,91)
Types of Bacteria Found in the GI Tract
The four dominant phyla residents in the human gut are Firmicutes (which contains lactobacilli), Bacteroidetes, Actinobacteria (which contains Bifidobacteria), and Proteobacteria. Other phyla found in lower numbers are the Fusobacteria and Verrucobacteria. Figure 7 presents the significant phyla, families, and genera of gut bacteria in terms of the number of records that cite them in the CAS Content Collection. This presentation reflects the relative level of research interest in each of these taxonomic groups. Most bacteria belong to the genera Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus, Peptococcus, Peptostreptococcus, and Bifidobacterium. Other genera, such as Escherichia and Lactobacillus, are present to a much lesser extent. Twenty-three species from the genus Bacteroides, alone, constitute about 30% of all bacteria in the human gut. (93)
Figure 7
Figure 7. Representation (as number of records) of the gut bacteria phyla and species in the CAS Content Collection.
Bacteroidetes
Bacteroidetes are Gram-negative, nonspore-forming, anaerobic or aerobic, rod-shaped bacteria. Bacteroides fragilis, found in the human microbiome, is the type of species for this phylum. The majority of the Bacteroidetes species fall into three genera: Prevotella (bile-sensitive, moderately saccharolytic, with pigmented and nonpigmented species), Porphyromonas (bile-sensitive, pigmented, asaccharolytic species), and Bacteroides (bile-resistant, nonpigmented, saccharolytic species). Other genera in the phyla are Alistipes, Anaerorhabdus, Dichelobacter, Fibrobacter, Megamonas, Mitsuokella, Rikenella, Sebaldella, Tannerella, and Tissierella. (94) Some members of the Bacteroides genus, although belonging to the normal gastrointestinal microbiota, can cause opportunistic infections if the integrity of the intestinal mucosal barrier is broken. These infections are usually polymicrobial, but B. fragilis and B. thetaiotaomicron are the most frequent species isolated. Some members of the genera Porphyromonas, Prevotella, and Tannerella are well-known pathogens of the oral cavity, where they can notably cause periodontal disease and dental caries. (95) The ability of some members of the Bacteroidetes to degrade polysaccharides explains why they thrive in the GI tract. (96)
Firmicutes
The Firmicutes phylum comprises Gram-positive bacteria with low G + C DNA content and is composed of more than 200 different genera, such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. (82) They can be found in a variety of places, including soil, water, skin, and the GI tract. The phylum includes aerobes, anaerobes, spore-forming, saprophytic, and pathogenic bacteria. Notable among the latter are Clostridium difficile and Listeria monocytogenes. Firmicutes, such as Clostridium botulinum, Clostridium tetani, Clostridium perfringens, and Staphylococcus aureus, can produce proteinaceous toxins. Other important genera are Listeria, Paenibacillus, Staphylococcus, Streptococcus, Pediococcus, and Leuconostoc. (97) Some members of Firmicutes are involved in bile acid metabolism in the gut. Accumulating evidence suggests that bile acids play pivotal roles in gut inflammation and the development of intestinal bowel disease (IBD). Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes. (98)
Actinobacteria
The Actinobacteria are Gram-positive bacteria with high G + C DNA content and constitute one of the largest bacterial phyla. They are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. The phylum includes pathogens (species of Corynebacterium, Mycobacterium, Nocardia, and Propionibacterium), soil inhabitants (Micromonospora and Streptomyces species), plant commensals (Frankia spp.), and GI commensals (Bifidobacterium spp.) (99) The Bifidobacteria are among the first microbial colonizers of the intestines of newborns and play key roles in the development of their physiology, including maturation of the immune system and use of dietary components. Some Bifidobacterium strains are considered probiotic microorganisms because of their beneficial effects, and they have been included as bioactive ingredients in functional foods, mainly dairy products, as well as in food supplements and pharma products, alone or together with other microbes or microbial substrates. (100)
Proteobacteria
The name Proteobacteria was first proposed by Stackebrandt et al. in 1988. (101) The name was derived from Proteus the ancient Greek god of the sea capable of assuming different shapes, which reflected the high heterogeneity displayed by the bacteria belonging to this phylum. A common trait of Proteobacteria is Gram-negative staining, which indicates the presence of lipopolysaccharide in the outer membrane. On the basis of phylogenetic analysis of the 16S rRNA gene, the Proteobacteria phylum is divided into six classes (previously regarded as subclasses of the phylum): Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, Epsilonproteobacteria, and Zetaproteobacteria. Considering that the classes division is based on molecular relatedness, it is not surprising that no specific morphological or physiological trait characterizes members within each class. (102) Notable genera in the Proteobacteria are Escherichia, Salmonella, Shigella, Desulfovibrio, and Helicobacter. Included in the phyla is the Enterobacteriaceae family, which contains several enteropathogenic bacteria, including Shigella flexneri, Salmonella typhi, and Escherichia coli. Other enteric pathogens in this phylum are Vibrio cholerae and Helicobacter pylori.
Verrucomicrobia
The phylum Verrucomicrobia, like the Proteobacteria, is defined by as a distinct phylogenetic lineage, as determined by 16S rRNA gene sequences. The phylum has been recognized as separate since 1995 but currently counts only a few cultivated microorganisms as members. Verrucomicrobia is a divergent phylum that includes members of the microbial communities of soil and fresh and marine waters. Some extremely acidophilic members from hot springs have been found to oxidize methane. (103,104) Akkermansia muciniphila is a mucus-degrading member of the Verrucomicrobia found in the human GI tract. A. muciniphila represents from 1 to 4% of the bacterial population in the colon. (105) A. muciniphila prefers to colonize in the intestinal mucus layer and specifically degrades mucins to produce short-chain fatty acids, thereby providing energy for the host and promoting colonization of the bacterium itself. The degradation of mucins prompts the host to compensate with the production of more mucins, thereby maintaining the dynamics of these proteins. (106)
Fusobacteria
The phylum Fusobacteria is made up of Gram-negative, nonmotile, facultative aerobic to obligately anaerobic, fermentative, rod-shaped bacteria, which have generally fusiform (spindle-shaped) morphology. Fusobacteria have been known for more than 100 years, but recently, phylogenetic studies have shown that they should be grouped into a distinct phylum. The bacteria from this phylum are commonly associated with the mucous membrane of humans and animals. They are also commonly present in the human and animal GI tract, particularly in the jejunum, the ileum, and the colon. (83,107)
Gut Microbiome–Disease Correlations
The human microbiome has been recognized as an essential factor for human health. (108−110) Specifically, gut microbes contribute directly and/or indirectly to important physiological activities, including immunomodulation and the regulation of various neurotransmitters, hormones, and metabolites. Dysbiosis is a state characterized by distinct alterations in the microbiome that result in an imbalance in the microbiota, modifications in their functional composition and metabolic performance, or a change in their allocation. The impact of the microbiome on human physiology and pathology is so extensive that the microbiome has been considered as an essential organ of the human body. (111−113) A search in the CAS Content Collection identified a large collection of studies reporting correlations between gut microbiota and a wide range of diseases, including mental, metabolic, and digestive system disorders; cardiovascular and neurodegenerative diseases; various cancers; and immune and autoimmune diseases (Figure 8). Trends in the number of publications related to various diseases in the recent years (2016–2021) are depicted in Figure 9. The number of documents related to dysbiosis, in general, exhibits the greatest growth rate, thereby characterizing the dominant fundamental approach of the recent studies in the field.
Figure 8
Figure 8. Distribution of the publications in the CAS Content Collection related to gut microbiome-associated diseases.
Figure 9
Figure 9. Trends in the number of publications concerning gut microbiome-related diseases during the years 2016–2021. Percentages are calculated with yearly publication numbers for each disease, normalized by the total number of publications for the same disease in the same time period.
Digestive System Diseases and Disorders
Alterations to the gut microbiota composition have been associated with various digestive system disorders and diseases, specifically IBS; IBD, including Crohn’s disease and ulcerative colitis; diarrhea, and constipation (Figure 8). (114−116)
Irritable bowel syndrome is one of the most prevalent functional gastrointestinal disorders and is considered as the prototype of disorders of the gut–brain interaction. While alterations in gut–brain interactions have clearly been established in IBS, a causative role of the microbiome remains to be determined. Dysbiosis is one of the hallmarks in the miscommunication between gut and brain and could lead to IBS symptoms. The severity of IBS symptoms has been shown to be correlated with dysbiosis. (117,118) In IBS cases, the reduction of microbiome diversity, gut barrier deficiency, gut–brain signaling disorders, and immune disorders are significantly related to the abnormal function of the GI tract. (119) Modifications in the composition of the normal microbiota and perturbed colonic fermentation in IBS patients are supposed to play a role in the development of IBS, with a considerable, nearly 2-fold, increase in the ratio of Firmicutes to Bacteroidetes. (120) Recent studies have reported well-defined distinction between gut microbiota composition in patients with IBS compared with healthy controls. IBS was typified by enhanced quantities of Firmicutes and specifically in Ruminococcus, Clostridium, and Dorea, along with a distinct decrease of beneficial microbes, such as Bifidobacterium and Faecalibacterium spp. (121) Moreover, a decrease in probiotic species and an increase in pathogenic species have been reported in patients with IBS, including Proteobacteria, Enterobacteriaceae, Lactobacillaceae, and Bacteroides (Bacteroidetes). (122) Fecal transplantation from super donors and microbiome modulation either by pro- or prebiotics have shown beneficial effect in reducing IBS symptoms and improving patients’ quality of life. (119,123,124) To date, the guidelines on the treatment of IBS with probiotics remain controversial. The British Society of Gastroenterology guidelines (125) on the management of IBS, which were updated in 2021, reported that probiotics may be an effective treatment for improving global symptoms and abdominal pain in patients with IBS, which was consistent with the recommendations of the Canadian Association of Gastroenterology (126) and the Japanese Society of Gastroenterology. (127) In contrast, the guidelines from the American College of Gastroenterology (128) suggest against the use of probiotics for the treatment of global IBS symptoms. (129)
Like IBS, inflammatory bowel disease-related dysbiosis is associated with a general decrease in richness, diversity, and stability of the microbiota. (130) This decline in diversity is concomitant with a weakened immune response and setbacks with the cellular barrier functions that normally block bacterial entry from the gut lumen into gut tissue. These malfunctions trigger complications with antibacterial defense and consequent growth of pathogenic bacteria. (131) IBD-related dysbiosis is specifically associated with a comprehensive decrease in the quantity and diversity of Firmicutes and an increase in Proteobacteria. (132) The decrease in the numbers of Firmicutes is noteworthy since they produce essential short-chain fatty acids, such as acetic and butyric acids, that are known to exhibit anti-inflammatory properties. (133) A common feature of the microbial dysbiosis among IBD patients, especially in Crohn’s disease, is the decreased abundance of Firmicutes bacteria belonging to two families that are important functional members of the human gut microbiota─Ruminococcaceae and Lachnospiraceae─to which most butyrate-producing bacteria in the human gut belong. (134,135) Thus, depletion of these bacterial families in IBD is supposedly correlated to the detected disturbances, such as a lower butyrate-producing capacity of the IBD microbiota. (136) Butyrate has a significant potential in IBD therapy because it serves as the colonocytes key energy source, enhances the epithelial barrier integrity, and inhibits inflammation. A probiotics treatment, including consumption of butyrate-producing bacteria to increase in situ butyrate production, may restore gut homeostasis. (137−139) A recent study reported that an orally delivered cocktail of bacteriophages targeting an IBD-associated strain of the bacterium Klebsiella pneumoniae alleviated intestinal inflammation. (131)
A growing body of evidence shows that imbalance of the gut microbiota increases susceptibility to various pathogens and causes numerous diseases, including diarrhea. (140) At present, the pathogens causing diarrhea are believed to be Escherichia coli, Shigella, Salmonella, Campylobacter, Clostridium difficile, and Aeromonas. (141,142) It has been found that microbial intervention can regulate the composition of the intestinal flora to prevent and improve the occurrence of diarrhea. (143) Probiotics containing nonpathogenic live bacteria preparations, such as Lactobacillus, Yeast, Bifidobacterium, Enterococcus, and Bacillus, have been demonstrated to treat pathogens-caused diarrhea by preserving or amending the balance of gut microbiota. The mechanisms of the beneficial effect are supposedly related to the inhibitory effect on the colonization of pathogenic bacteria by competing for nutrients and producing antibacterial compounds. (144)
Accumulating evidence suggests an association between functional constipation and abnormal gut microbiota, with the relationship between gut microbiota and gut transit being likely bidirectional. (145) By controlling colonic motility, water content, secretion, and absorption, gut microbiota may promote the development of functional constipation through microbial metabolites, including bile acids, SCFAs, 5-hydroxytryptamine, and methane. Currently, there is no consensus on the gut microbial composition typical for functional constipation patients and the alteration trends of the various microbial classes compared with healthy controls. (146−150) However, recent studies showed that changes in the mucosal and fecal microorganisms are linked to functional idiopathic constipation. Taxonomic profiling of intestinal microbiota in constipated adults showed a higher abundance of Bacteroides and other pathogenic microorganisms than in healthy volunteers. (151) The increased richness and diversity of the gut microbiomes result in slow colonic transit. In addition, intestinal microbiota in constipated adults have genes involved in pathways that lead to methane, hydrogen, and glycerol production, which can explain the symptoms seen in patients with constipation. (151−153) Microbial interventions including probiotics, prebiotics, and synbiotics, which bring about compositional and functional changes of the gut microbiota, have frequently shown beneficial effects on functional constipation that are in favor of the concept of the significant role of gut microbiota in functional constipation. (145) This concept is supported also by the reports that many risk factors of functional constipation, including age, diet, obesity, and stress, have a considerable effect on the gut microbiota. (154,155)
Mental and Neurodegenerative Disorders
Gut microbiota have been reported to affect neurological functions along the so-called gut–brain axis (GBA). (156) Gut microbiota communicates with the brain through three major routes: the neural route (vagus nerve, enteric nervous system), the immune route (cytokines), and the endocrine route [hypothalamus–pituitary–adrenal (HPA) axis, gut hormones]. Disturbances in any of these routes can result in mental disorders. Dysbiosis in common intestine microbial species of the phylum Firmicutes and Actinobacteria and the genera Bacteroides and Bifidobacterium are supposedly responsible for mental health disorders. (157) Gut microbiota moderate the GBA via various ways, such as preserving gut permeability by controlling the integrity of tight junctions in gut epithelium and producing a large selection of metabolites that include neurotransmitters, SCFAs, and amino acids.
A plethora of research reports have indicated the significance of microbiota in the development of neurodegenerative diseases via a variety of microbial metabolites that transmit from the gut to the brain across the GBA. (158,159) Changes in the levels of gut microbial metabolites have been reported to be associated with neurological conditions like Parkinson’s disease, (160) anorexia nervosa, (161) Alzheimer’s disease, (162) autism spectrum disorders, (163) and chronic stress and depression. (164) It is not clear by now, however, whether these disruptions in mental health are the cause or a result of the changes in gut microbiota. Gut dysbiosis has been associated with increased gut permeability and inflammation and it may also cause enhanced levels of circulating gut microbiota metabolites, such as the neurotoxin β-N-methylamino-l-alanine and microbial amyloids. (165,166) β-N-Methylamino-l-alanine is one of the gut cyanobacteria-produced neurotoxins causing neurodegeneration, cognitive impairment, and the accumulation of neurofibrillary tangles. (167,168) The hypothesis that Parkinson’s disease starts in the gut and spreads to the brain (169) is gaining increasing support, thereby showing that the disease is associated with widespread dysbiosis. (170)
Alterations in the microbiota composition in patients with Alzheimer’s disease compared with matched healthy controls included a reduction in richness and diversity of gut microbiota with decreased Firmicutes and Bifidobacterium and increased Bacteroidetes. (171) Changes in Actinobacteria, Ruminococcus, Lachnospiraceae, and Selenomonadales (1686) have also been reported. (172) Cognitively impaired patients exhibited alterations in Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia compared with age-matched cognitively intact individuals. (173)
Therapeutic interventions including the administration of pre- and probiotics (psychobiotics) to manage mental disorders and/or their symptoms have been undertaken. (174,175) These inventions have included probiotic combinations of lactobacilli and Bifidobacteria, which has resulted in a significant drop in psychological distress, (176) enhanced cognition and communication among patients with Alzheimer’s disease (177) and autism spectrum disorders, (178) and recovering symptoms among patients with Parkinson’s disease. (179) On the basis of the promising results of psychobiotics on controlling or modulating the GBA, additional clinical trials are currently being undertaken to identify bacterial strains as promising candidates for the treatment of mental disorders.
Humans are adapted to a circadian rhythm of 24 h associated with the light/dark cycle on earth. The central circadian clock is located in the hypothalamus, which synchronizes information on environmental light and dark signals to peripheral tissues to keep the body functioning in the same rhythm. (180) A disruption of circadian rhythms is associated with various diseases, including neurodegenerative diseases, sleep, and psychiatric disorders. (181,182) Recent studies have reported that gut microbiota are able to control or be controlled by the circadian clock. The mechanisms of such a relationship requires small molecule gut microbiota metabolites, such as bile acids and SCFAs, to act as intermediaries. (180) Thus, the levels of butyrate and propionate show obvious daily oscillations. Moreover, these oscillations are lost under high-fat diets. (183) The impacts of gut microbiota metabolites on circadian rhythm are extensive and are connected to other functions of gut microbiota metabolites, such as energy metabolism and immunity. These interconnections between different physiological functions via the link of gut microbiota metabolites are essential for understanding the functions of gut microbiota metabolites and the general role of gut microbes in human health and disease.
Metabolic Disorders
Systemic metabolic diseases that are believed to be strongly affected by gut microbiota status include obesity and diabetes. (184) Gut microbial composition is strongly affected by dietary routines. As a result of a high-fat diet, the intestinal microbiome is modified with rising amounts of Firmicutes and Proteobacteria and reduced levels of Bacteroidetes. The Firmicutes/Bacteroides ratio has been correlated to body weight, which means it is larger for obese people. (185) Clostridium difficile infections can also trigger obesity. Generally, obesity is affected by the inflammatory status induced by gut bacteria or their metabolites, which regulate the GBA. (108,185)
Diabetes is another metabolic disease that is strongly associated with the gut microbiome. Studies have reported an increased quantity of Villanella, Clostridium, and Bacteroides and a decreased quantity of Lactobacillus, Eubacterium rectale, Blautia coccoides, and Bifidobacterium in children with type 1 diabetes. Besides, negative correlation has been reported between plasma glucose level and Bifidobacterium, Lactobacillus spp., and Firmicutes and Bacteroidetes spp., while there has been positive correlation between Clostridium and plasma glucose level. The ratios of Bacteroidetes to Firmicutes were reported to exhibit a positive connection with plasma glucose levels. The Lactobacillus genus was also in lower quantity in type 2 diabetes patients, and Bifidobacterium was in higher quantity compared with control groups. (108,186) Risks for the development of type 2 diabetes have been correlated to the composition of gut microbiota, as well. The alterations in the gut microbiota of individuals with type 2 diabetes have been small compared with the control group, yet a consistent decline in the metabolically beneficial butyrate-producing bacteria was reported. (186) Overall, type 2 diabetes was associated with a reduced quantity of SCFAs-producing bacteria, in particular butyric acid, which has been related to insulin sensitivity. (187,188) The relation between SCFAs and insulin sensitivity stems from the capacity of SCFAs to stimulate the secretion of GLP-1 by intestinal L-cells via G protein receptors, which has a significant impact on insulin release. (189)
Close relations between the metabolic and immune systems are now largely supported, and intestinal microbiota is being progressively identified as an important factor connecting genes, environment, and the immune system. (190)
COVID-19
Recently, correlation has been reported between gut microbiota composition and levels of cytokines and inflammatory markers in patients with COVID-19. (191,192) It is suggested that the gut microbiome is involved in the magnitude of COVID-19 symptoms’ severity via modulation of the host’s immune responses. Moreover, gut microbiota dysbiosis could contribute to persistent symptoms even after disease resolution, thereby emphasizing a need to understand how gut microorganisms are involved in inflammation and COVID-19.A recent study demonstrated that SARS-CoV-2 infection indeed disrupts the gut microbiome. (193) This boosts secondary bacterial infections both by facilitating pathogenic bacteria to colonize the gut and by modifying gut lining to allow these bacteria to spread from the gut to the bloodstream of COVID-19 patients. These results confirm the direct role of gut microbiome dysbiosis in facilitating grave secondary infections upon COVID-19 malady. (193)
The alterations to the gut microbiota composition related to digestive system diseases, mental health, and metabolic disorders are summarized in Table 1.
Table 1. Gut Dysbiosis in Digestive System Diseases, Mental Health, and Metabolic Disorders
| diseases | ↓ decreasing bacteria | ↑ increasing bacteria |
|---|---|---|
| digestive system diseases | ||
| irritable bowel syndrome (194−199) | Bifidobacterium | Ruminococcus |
| Faecalibacterium prausnitzii | Dorea | |
| Bacteroides | Enterobacteriaceae | |
| Lactobacillaceae | ||
| Bacteroides | ||
| Firmicutes/Bacteroidetes ratio | ||
| IBD: Crohn’s disease (200,201) | Bacteroides | |
| Faecalibacterium prausnitzii | ||
| Bifidobacterium adolescentis | ||
| IBD: ulcerative colitis (139,200) | Bifidobacteria | |
| Roseburia hominis | ||
| Faecalibacterium prausnitzii | ||
| Lachnospiraceae | ||
| Ruminococcaceae | ||
| mental health disorders | ||
| anxiety disorder (202,203) | Bacteriodetes | Bacteroidaceae |
| Ruminococcus gnavus | Enterobacteriaceae | |
| Fusobacterium | Burkholderiaceae | |
| post-traumatic stress disorder (204) | Actinobacteria | |
| Lentisphaerae | ||
| Verrucomicrobia | ||
| depression (205−207) | Prevotella | Eggerthella |
| Dialister | Holdemania | |
| Turicibacter | ||
| Paraprevotella | ||
| dementia (172) | Actinobacteria | Escherichia |
| Bacteroides | Blautia | |
| Bifidobacterium | ||
| Streptococcus | ||
| Lactobacillus | ||
| Dorea | ||
| metabolic disorders | ||
| diabetes type 1 (208,209) | Lactobacillus | Clostridium |
| Bifidobacterium | Bacteroides | |
| Blautia coccoides | Veillonella | |
| Eubacterium rectale | Actinobacteria | |
| Prevotella | Proteobacteria | |
| Akkermansia | Lactococcus | |
| Firmicutes | ||
| diabetes type 2 (199,209,210) | Firmicutes | Betaproteobacteria |
| Clostridia | ||
| Lactobacillus | Bacteroidetes/Firmicutes ratio | |
| Akkermansia muciniphilia | ||
| Roseburia | ||
| obesity (199,211) | Bacteroidetes | Enterobacteria |
| Methanobrevibacter smithii | Ruminococcus gnavus | |
| Ruminococcus flavefaciens | Actinobacteria | |
| Bifidobacterium | Prevotellaceae | |
Gut Bacteria–Disease Correlations
In an effort to get better insight into the gut microbiota impact on well-being, we explored the correlations between the major classes of gut bacteria and certain mental and gastrointestinal disorders, as reflected in the number of records in the CAS Content Collection (Figure 10).
Figure 10
Figure 10. Correlation between major classes of gut bacteria with mental and gastrointestinal disorders, as reflected in the number of associated records in the CAS Content Collection.
As seen from Figure 10, Bacteroidetes are the most studied class of gut bacteria with relation to gastrointestinal and mental health, specifically with relation to stress, depression, and anxiety. Bacteroidetes are known to have a very broad metabolic potential and are regarded as one of the most stable parts of gastrointestinal microflora that exhibits remarkable nutritional flexibility and an ability to respond to stress. (212) However, the exact mechanisms underlying any possible relationship between Bacteroidetes and mental and gastrointestinal health remains unclear, and further research is needed to fully understand this complex relationship.
Firmicutes are the second extensively studied class of gut bacteria with relation to gastrointestinal and mental health, especially in relation to stress and depression (Figure 10). Many members of the Firmicutes phylum, such as Lactobacillus, are probiotic. The relationship between Firmicutes and gastrointestinal disorders may be mediated by a number of different factors, such as the production of SCFAs by Firmicutes, which are an important energy source for the gut epithelium and have anti-inflammatory effects. In addition, some Firmicutes bacteria are involved in the fermentation of complex carbohydrates and the production of beneficial metabolites, such as butyrate, which has been shown to have protective effects against colorectal cancer. (213) Like with Bacteroidetes, the exact relationship between Firmicutes and mental and gastrointestinal disorders is still being studied and is not fully understood.
The interest in Fusobacteria with respect to the gastrointestinal and mental health is mainly related to diarrhea and constipation (Figure 10). Recent evidence is emerging that this bacterium may be related to human colon cancer. (214)
It is noteworthy that recent meta-analysis has reinforced the genetic correlations between Alzheimer’s disease and the gut microbiome genera. (215) For example, genus Actinobacterium Collinsella was confirmed to be associated with Alzheimer’s disease, as well as rheumatoid arthritis, atherosclerosis, and type 2 diabetes. (215) It is also worth reiterating that the gut microbiota is a complex and diverse community of microorganisms, and changes in any one particular phylum are unlikely to fully explain the development of any particular disorder or condition. Rather, the gut microbiota as a whole are likely to play a role in shaping our physical and mental health, and further research is needed to fully understand the complex relationships between the gut microbiota and overall well-being.
Therapeutic Strategies for the Treatment of Mental and Gastrointestinal Disorders
Imbalances within the gut microbiome–brain axis have been linked to a range of mental and gastrointestinal disorders. Assorted therapeutic interventions aimed at modulating the gut microbiome or the gut–brain axis may be effective in improving outcomes for these conditions.
Dietary Interventions
A high-fiber diet can increase the production of SCFAs, which can help to maintain gut barrier function and reduce inflammation. SCFAs can also promote the growth of beneficial gut bacteria, which can outcompete pathogenic bacteria and reduce inflammation. (216)
A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can reduce symptoms in individuals with irritable bowel syndrome by reducing the fermentation of certain carbohydrates in the gut, which can cause symptoms such as bloating and abdominal pain. However, the low-FODMAP diet can also reduce the diversity of gut bacteria and may have negative long-term effects on gut health. (217,218)
Probiotics and Prebiotics
Probiotics can improve gut barrier function by enhancing the production of mucus and tight junction proteins, which can prevent the entry of harmful molecules and pathogens into the bloodstream. They can also reduce the production of proinflammatory cytokines and modulate the activity of immune cells in the gut, thereby promoting an anti-inflammatory response. (219,220)
Prebiotics can increase the production of metabolites, such as SCFAs, which are important energy sources for gut cells and can help to maintain gut barrier integrity. SCFAs can also activate G protein-coupled receptors on immune cells, thereby leading to the production of anti-inflammatory cytokines and the suppression of proinflammatory cytokines. (221,222)
Antibiotics
Antibiotics can kill harmful bacteria in the gut, which reduces inflammation and restores gut barrier function. However, antibiotics can also have negative effects on the gut microbiome, such as by reducing the diversity of gut bacteria and promoting the growth of antibiotic-resistant bacteria. Antibiotics should be used judiciously and only when necessary. (223,224)
Fecal Microbiota Transplantation (FMT)
FMT can restore the composition and function of the gut microbiome, which can reduce inflammation and improve gut–brain communication. FMT has been shown to be effective in treating recurrent Clostridium difficile infection and is being investigated for other conditions, such as IBD and autism. (225−227)
Psychotherapeutic Interventions
Psychotherapeutic interventions can reduce stress and improve gut–brain communication. Stress can disrupt gut microbiome composition and function, which leads to inflammation and the development of diseases related to the gut microbiome–brain axis. The reduction of stress can be an effective way to improve gut health and reduce symptoms in these conditions. (228−230)
Pharmacological Interventions
Drugs that target the gut–brain axis can modulate gut microbiome composition and function and reduce inflammation. For example, certain drugs that target the serotonin system, such as selective serotonin reuptake inhibitors (SSRIs), can modulate gut–brain communication and have been shown to be effective in treating conditions, such as depression and anxiety. (231,232)
Figure 11 demonstrates the annual growth in the number of documents in the CAS Content Collection related to various therapeutic interventions applied for the treatment of mental and gastrointestinal disorders. Fecal transplant as a new therapeutic strategy exhibits the fastest growth rate recently.
Figure 11
Figure 11. Trends in the therapeutic strategies applied for the treatment of mental and gastrointestinal disorders, as presented in the documents related to gut microbiome research during the years 2017–2021. Percentages are calculated with yearly publication numbers for each type of therapeutic intervention normalized by the total number of publications for the same intervention in the same time period.
The various strategies to treating diseases related to the gut microbiome–brain axis can work through multiple mechanisms, including modulating gut microbiome composition and function, reducing inflammation, and improving gut–brain communication. (233) However, the underlying mechanisms are complex and require further research to fully understand.
Gut Microbiota Metabolites
ARTICLE SECTIONS
It is estimated that the human gut microbiome contains more than 22 million microbial genes, (234) which exceeds the ∼22,000 genes present in the entire human genome. (235) These genes enable the gut microbiota in the host to synthesize a myriad of enzymes with versatile capabilities to ferment and degrade a variety of compounds that humans do not have the genetic machinery to metabolize. As a result, the gut microbiota can generate a battery of metabolites with a wide spectrum of bioactivities. The gut microbiota-derived metabolites can be broadly divided into three types according to their origination: (1) metabolites that are produced by gut microbiota directly from diets; (2) metabolites that are generated by the host and modified by gut microbiota; (3) metabolites that are produced de novo. (236) A selection of important gut microbiota metabolites related to gut–brain communication is shown in Table 2.
Table 2. Exemplary Gut Microbiota Metabolites, as Represented in the CAS Content Collection
Gut Microbiota Metabolites with Impact on Brain Function
The gut microbiota provides essential signaling metabolites that are vital for the host’s physiology. While in healthy individuals, gut microbiota metabolites are effective in maintaining the important functions of hosts, perturbations in the production of these metabolites can initiate various diseases, such as digestive system diseases, neurodegenerative and metabolic disorders, and cancer. (236)
Research has shown that gut microbiota is crucial for normal brain development and function. (237,238) For example, administration of 4-ethylphenylsulfate (4-EPS), a tyrosine derivative, to mice at 3–6 weeks postnatal induced anxiety-like behavior. The biosynthetic pathway analysis and mechanisms behind the detrimental effects of 4-EPS showed that 4-EPS interfered with oligodendrocyte maturation, myelination, and brain activity patterns. p-Cresol, another tyrosine derivative and a metabolite, has also been directly associated with neurodevelopmental disorders. (239,240) Further, certain bacteria-related metabolites, such as trimethylamine-N-oxide (TMAO), 5-aminovaleric acid (5-AVA), 5-AVA betaine (5-AVAB), imidazolepropionic acid, and hippuric acid have been reported to promote early-life axonogenesis both in vitro and in vivo. (241) Moreover, the neurogenic properties of microbe metabolites may not be limited to early life given that indole, a tryptophan metabolite, has been reported to increase neurogenesis in the hippocampus of adult mice. (242) Pilot studies using fecal microbiota transplantation in children enabled the assessment of whether early life interventions affecting the gut microbiota composition exerted long-term neurodevelopment effects. (243,244) Thus, maternal fecal microbiota transplantation in cesarean-born infants was found to rapidly restore normal gut microbial development. (244)
Gut microbiota and its metabolites can affect the host metabolism of neuroactive compounds. (245) The foremost examples of gut bacteria-derived neurotransmitters are aromatic amino acid derivatives dopamine and norepinephrine and glutamate derivative γ-aminobutyric acid. (246,247) Microbiota have been found to extensively contribute to the levels of dopamine and norepinephrine via the activity of β-glucuronidase. (248) Kynurenic acid, a tryptophan metabolite, functions as a glutamate modulator to reduce glutamate levels in the glutamatergic signaling in the hippocampus. Thus, enhanced cognitive abilities and memory in model animals have been achieved as a result of enhancing glutamate levels via limiting hippocampal kynurenic supply. (249,250) Over 90% of serotonin in the body is known to be produced in the gut in a process in which gut microbes play an important regulatory role. (251,252) Tyramine, deoxycholic acid, and 4-aminobenzoic acid have been reported to stimulate serotonin synthesis. (252) Furthermore, microbiota-related metabolites, such as norepinephrine, indole, indole-3-aldehyde, isovaleric acid, butyric acid, and isobutyric acid stimulate serotonin release from enterochromaffin cells. (253,254) Another gut microbiota metabolite with a likely connection to γ-aminobutyric acid (GABA) expression in brain is lactate. (255,256) It has been shown to affect neural plasticity and has a beneficial effect on learning and memory in model animals. (257) SCFAs, particularly butyric acid, may also have additional regulatory effects on the signal transduction to the brain via the vagal nerve and by inducing the biosynthesis of neurotransmitters in the CNS. (258) Administration of SCFAs, such as butyric, acetic, and propionic acid, has been reported to improve stress response, anxiety, and depression. (259) The presence of pipecolic acid in the CNS can be partially derived from the gut microbiota and has been also associated with GABA signaling and release. (245,260,261)
Gut microbiota has also proven vital for normal BBB function, especially during pre- and postnatal periods. (262) In a mice model of traumatic brain injury typified by acute BBB disruption, sodium butyrate administration exhibited an alleviating effect on BBB integrity. (263) Propionic acid, another SCFA gut microbiome metabolite, has also been shown to promote BBB integrity by mitigating oxidative and proinflammatory pathways. (264) It has been suggested that the effects of SCFAs on BBB integrity may rather be brought about by peripheral signaling instead of direct uptake to the brain, as implied by animal models. (258) Secondary bile acids, such as deoxycholic acid and ursodeoxycholic acid, may also modulate BBB integrity. (265,266) Trimethylamine, a metabolite of dietary choline, betaine, and l-carnitine, has been reported to exert detrimental impact on the BBB integrity. It is noteworthy that physiologically appropriate doses of the oxidized form of trimethylamine, TMAO, improved the BBB integrity. (267)
A large portion of the brain’s energy production is consumed by the neurons, the major component of the nervous tissue, in order to maintain the excitability of the synapses. (268) Lactate, a major gut microbiota metabolite, is known to augment neural activity as a primary energy source. (269) Modulation of brain energy metabolism in the hippocampus along the GBA is suggested to be responsible for improvement in the cognitive function after intermittent fasting in model animals. (270) It has been found that fasting considerably increased plasma levels of indolepropionic acid and tauroursodeoxycholic acid and fecal levels of SCFAs. Administrations of indolepropionic acid or tauroursodeoxycholic acid or a SCFAs mixture including acetic, propionic, and butyric acid have been able to reproduce the effects of fasting in cognition, hippocampal mitochondrial biogenesis, and energy metabolism-related gene expression. Findings connecting microbial metabolites to brain bioenergetics are preliminary but show that certain compounds are incorporated in the neuronal energy metabolism.
Gut microbiota metabolites reducing oxidative stress or neurotoxic proteins aggregation are functioning as neuroprotective agents. Metabolites that reduce inflammation or promote neurodevelopment or neurotransmission can also be considered as neuroprotectants. For example, ferulic acid is known to be metabolized by gut microbes. (271) It exerts neuroprotective effects by reducing neuronal cell death and recovers memory deficits in a cerebral ischemia and reperfusion injury model. (272) It has also ameliorated depressionlike behavior and oxidative stress. (273) Dihydroferulic acid, a microbiota metabolite, has also been shown to exhibit neuroprotective antioxidative properties. (274)
The gut microbiome metabolites and their mechanism of action in mental health and brain development are depicted in Figure 12, and their function and associated diseases are summarized in Table 3.
Figure 12
Figure 12. Exemplary gut microbiome metabolites and their mechanism of action in gut–brain communications.
Table 3. Gut Microbiota Metabolites, Their Function, and Associated Diseases
| metabolite class/references | specific functions | associated diseases |
|---|---|---|
| short-chain fatty acids (258,285−290) | – gut microbiota composition regulation | – diabetes |
| – gut barrier integrity support | – obesity | |
| – energy homeostasis support | – nonalcoholic fatty liver disease | |
| – gut hormone production | – ulcerative colitis | |
| – circadian rhythm regulation | – Crohn’s disease | |
| – proinflammatory cytokines inhibition | – colorectal cancer | |
| – immunomodulation | – autism spectrum disorder | |
| – water, sodium, calcium, magnesium absorption | – Parkinson’s disease | |
| – regulation of intestinal pH value | – diarrhea | |
| – IBS | ||
| – constipation | ||
| – functional dyspepsia (FD) | ||
| bile acids (BAs) (291−295) | – lipid and vitamin absorption regulation | – obesity |
| – gut microbiota composition regulation | – nonalcoholic steatohepatitis | |
| – gut hormones production | – ulcerative colitis | |
| – intestinal immunity | – cancer | |
| – intestinal electrolyte and fluid balance | – multiple sclerosis | |
| – gut motility | – Alzheimer’s disease | |
| – gut barrier integrity | – Parkinson’s disease | |
| – lipid homeostasis | – traumatic brain injury | |
| – glucose homeostasis | – stroke | |
| – amino acid homeostasis | – amyotrophic lateral sclerosis | |
| – circadian rhythm | – IBS | |
| – neurotransmission | ||
| tryptophan and indole derivatives (296−300) | – gut microbial spore formation | – ulcerative colitis |
| – drug resistance | – Crohn’s disease | |
| – biofilm formation | – obesity | |
| – intestinal barrier function regulation | – stroke | |
| – gut hormone secretion | – mucosal candidiasis | |
| – gut motility | – autism spectrum disorder | |
| – immunomodulation | – Alzheimer’s disease | |
| – Parkinson’s disease | ||
| – migraine | ||
| – schizophrenia | ||
| – IBS | ||
| choline metabolites (301−303) | – bile acid synthesis inhibition | – nonalcoholic fatty liver disease |
| – inflammation promotion | – obesity | |
| – thrombosis | – diabetes | |
| – myocardial hypertrophy and fibrosis | – hypertension | |
| – mitochondrial dysfunction exacerbation | ||
| vitamins (304−306) | – cellular metabolism regulation | – vitamin-associated diseases |
| – immunomodulation | – schizophrenia | |
| – cell proliferation | – autism | |
| – vitamins supply | – dementia | |
| – IBS | ||
| – IBD | ||
| neurotransmitters (307−309) | – gut motility regulation | – Parkinson’s disease |
| – memory support | – autism spectrum disorder | |
| – stress response | – IBD | |
| – nervous system | – IBS | |
| – immune response | ||
| lipids (184,310,311) | – systemic inflammation promotion | – diabetes |
| – hyperinsulinemia regulation | – obesity | |
| – immunomodulation | – nonalcoholic fatty liver disease | |
| – bile acid synthesis | – hyperinsulinemia | |
| – hypercholesterolemia | ||
| – chronic hepatitis C | ||
| gases (307,312−316) | – gut motility | – colitis |
| – gut inflammation | – ulcer | |
| – epithelial secretion | – IBS | |
| – mucosal blood flow |
Gut Microbiota Metabolites’ Role in Digestive System
Gut microbiota imparts specific function in the host’s digestive system, in nutrient metabolism, xenobiotic and drug metabolism, in preservation of the integrity of the intestinal mucosal barrier, and in protection against pathogens (Figure 13).
Figure 13
Figure 13. Gut microbiome metabolite classes and their roles in digestive system functions.
Gut microbiota mostly get nutrients from dietary carbohydrates. Fermentation of the carbohydrates, including indigestible oligosaccharides by the microbes in the colon, such as Bacteroides, Roseburia, Bifidobacterium, Faecalibacterium, and Enterobacter, ends in the synthesis of SCFAs, such as butyric, propionic, and acetic acids, which are important sources of energy for the host. (275) Gut microbiota have a positive role in lipid metabolism, as well, by controlling the lipoprotein lipase activity inhibition in adipocytes. (31)
Intestinal microbiota also exhibit a resourceful protein metabolizing machinery, which operates by means of the microbial proteinases and peptidases in conjunction with the human proteinases. Examples include the conversion of l-histidine into histamine by the bacterial enzyme histamine decarboxylase and glutamate to γ-amino butyric acid by glutamate decarboxylases. (276,277)
SCFAs can regulate the pH value in the intestine and regulate the absorption of water, sodium, calcium, and magnesium. Furthermore, SCFAs, especially butyrate, provide more than 70% of the energy for the intestinal epithelial cells on top of their abilities to inhibit the multiplication and growth of pathogenic bacteria and the activity of intestinal inflammatory mediators, thus playing an anti-inflammatory role in the intestinal tract. (278)
Lipid metabolites can affect intestinal permeability and intestinal immunity. The gut microbiota can produce lipopolysaccharides that could stimulate proinflammatory mediators, thereby disrupting the body’s immune system and inducing local and systemic inflammatory responses. (279) Sphingolipids can be produced by the intestinal symbiotic bacteria Bacteroidetes and Prevotellaceae. It has been found in animal studies that sphingolipids can also aggravate intestinal inflammation. (280)
Indole-derived metabolites are produced by fermentation via Clostridium sporogenes and Escherichia coli. Such metabolites are able to participate in the regulation of gastrointestinal disorders by influencing the gut–brain axis and protecting against stress-induced damage in the gastrointestinal tract. Tryptophan is a key monoamine neurotransmitter involved in the regulation of central neurotransmission and intestinal physiological functions, and studies have shown that the gastrointestinal microbiome can regulate the gut–brain axis through tryptophan metabolism. (281,282)
Gases can be produced by gut microbiota as a result of the fermentation process. These gases include hydrogen (H2), methane (CH4), carbon dioxide (CO2), hydrogen sulfide (H2S), and nitric oxide (NO), which can modulate the gastrointestinal physiology of hosts. (236)
Xiao et al. (283) in a recent review article highlighted the important microbial metabolites in the context of host physiology in patients with different IBS subtypes. The abundance of microorganisms and their corresponding metabolites in constipation-predominant IBS (IBS-C) and diarrhea-predominant IBS (IBS-D) differ, thereby providing a new avenue for the diagnosis and treatment of different IBS subtypes in the future. These microbiota-derived metabolites, such as bile acids (BAs), SCFAs, vitamins, amino acids, 5-HT, and hypoxanthine, can be produced directly by bacteria, or from dietary or relevant substrates. Fluctuations and alterations in the levels of metabolites produced by the host or microbiota provide insights into their interactions during IBS. Moreover, low levels of hypoxanthine may be associated with colonic epithelial energy and capacity for mucosal repair with hypoxia. Purine starvation has been identified as a potential novel mechanism underlying IBS with lower fecal hypoxanthine abundance in IBS-C and IBS-D. Additionally, mucosal biofilms are an endoscopic feature of IBS and are associated with bacterial and BA metabolites dysbiosis. Additionally, deficiency in levels of both vitamins D and B6 have emerged as causative factors in IBS symptoms pathogenesis. (283)
Microbial dysbiosis and metabolites derived from interaction of the host and gut microbiota have been reported as an intermediate link contributing to the development of functional constipation via various signal pathways, including but not limited to SCFAs, BAs, and methane that occupied a more important position. (153) 5-HT is also involved in the modulation of gut motility and secretory, as well as sensory, transmission in patients with constipation. (284) Altogether, current studies have provided us with a new conception on the microbial mechanisms and therapeutic targets of constipation.
The gut microbiome metabolites and their function and associated digestive diseases/disorders are summarized in Table 3.
Gut Microbiome–Brain Axis
ARTICLE SECTIONS
CNS and the human GI tract communicate through the gut–brain axis (GBA). This bidirectional connection involves neuronal, endocrine, and immunological mechanisms. The gut is considered as our “second brain,” because of its hosting the enteric nervous system (ENS), a neural network that allows the gut to work without instructions from the brain. The ENS maintains control of our digestive system; it plays an important role in peristalsis, secretion, and pain perception. There is mounting data that gut microbiota are the source of a number of neuroactive and immunocompetent substances, as shown above, that help to shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity and contribute to the proper maintenance of gastrointestinal homeostasis. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors. (317)
Functional gastrointestinal disorders (FGIDs) were previously considered as purely functional disorders with no scientific confirmation of a clear pathogenetic mechanism. According to Rome IV, the phenotype of FGIDs results from an altered transmission of nerve and biochemical signals within the gut microbiome–brain axis with mechanisms controlled by both genetic and environmental factors. Consequently, FGIDs were recently renamed into disorders of gut–brain interactions. (318) The overlap of DGBI and CNS disorders has been documented, and it has been demonstrated that approximately one-third of IBS patients suffer from depression. It is estimated that psychiatric symptoms occur in at least 36.5% of FGIDs patients. Stasi et al. found that the highest prevalence of mental or spectrum disorders is in patients with functional constipation (60%) compared with patients diagnosed with FD (52.4%), IBS (36.5), and/or functional bloating (47.6%). The most prevalent psychiatric disorders observed in FGIDs were general anxiety disorder and panic. (319)
Recent advances in this field have enabled us to better understand some of the pathophysiological consequences of an aberrant reciprocal gut–brain network, including exacerbated gut inflammation disorders, altered responses to stress, as well as altered behavioral states. Therefore, the GBA presents an attractive target for the development of novel therapeutics for an ever-growing list of disorders related to mental and digestive health. Improved targeting of the gut microbiome–brain axis, for example through application of biotics, is expected to pave the way for the development of novel disease therapies and self-care products to promote and maintain heathy status. (320)
Irritable Bowel Syndrome
IBS is one of the most common DGBI worldwide and typically presents in early adulthood with symptoms including abdominal pain, bloating, and altered bowel habits. On the basis of the bowel habits, IBS can be classified into four subtypes: constipation-predominant, diarrhea-predominant, mixed-type (IBS-M), and undefined IBS (IBS-U). Symptom intensity varies over time and between individuals, but IBS has been reported, in severe cases to affect quality of life as much as renal impairment or diabetes. (321) IBS represents up to 50% of all referrals to gastroenterologists with a prevalence rate of up to 11% globally. (322) The recent consensus view is that IBS results from abnormal gut–brain interactions. Recent epidemiological data has suggested that in individuals developing both IBS and psychological features, the former preceded the latter in two-thirds of cases, and the latter preceded the former in one-third. (323) IBS is associated with abnormalities of central pain processing but also increased gut permeability, mast cell activation, disordered motility, and dysbiosis.
A recent genome-wide analysis study for 53 400 IBS patients and 433 201 controls highlights shared genetic pathways between IBS and mood and anxiety disorders. The study identified and confirmed six genetic susceptibility loci for IBS, and four of them are associated with mood and anxiety disorders, thereby suggesting, for example, that shared pathogenic pathways rather than anxiety cause abdominal symptoms. (324)
5-HT signaling is one particular pathway of importance in IBS pathogenesis. It has been demonstrated that a functional GI tract involves 5-HT signaling between enterochromaffin cells acting as sensory transducers, and the majority of 5-HT is synthesized, stored, and released by these cells, which interact with intrinsic and extrinsic sensory nerve afferents in the mucosal layer of the gut. (320) 5-HT signaling controls many GI functions, including secretion; vasodilation; peristalsis; and sensory perception, such as pain and nausea. (325−327) Moreover, serotonergic function and tryptophan metabolism are known to be altered in IBS patients. (328−331)
IBS pathophysiology implicates altered gut microbiota composition, impaired intestinal mucosal integrity, and low-grade inflammation. In addition to pathways through the circulatory system, several of these factors may also trigger fluctuations in the activity of the ENS with subsequent effect on the brain. (332) Furthermore, the vagus nerve can be modulated by diet-responsive gut microbes and metabolites, such as short-chain fatty acids, or endocrine factors, enzymes, and neurotransmitters, such as serotonin, dopamine, acetylcholine, glutamate, γ-aminobutyric acid, and noradrenaline. (333−336) Each of these factors are potentially affected by alterations in microbiota composition and are involved in IBS pathology. (337)
Identifying a clear IBS microbial signature is not an easy task because of the heterogeneity of the healthy gut microbiota. However, multiple studies have shown differences in the gut microbiota between IBS and healthy controls. A recent systematic review showed that IBS patients have increased levels of the bacterial families Enterobacteriaceae, Lactobacillaceae, and Bacteroidales, whereas Bifidobacterium, Faecalibacterium, and Clostridiales were decreased compared with healthy controls. (122) On the contrary, Hugerth et al. recently reported no distinct microbiota signature of IBS in a random Swedish population of 3556 participants. (338) Interestingly, intestinal bacterial composition has been reported to be highly dependent on sample type and regional localization. Also, mucosa-associated bacterial composition of the sigmoid colon differs between patients with IBS and healthy controls. (339)
One of the most consistent findings in brain neuroimaging of IBS patients has been alterations in the structure and function of key regions of the somatosensory network, including the globus pallidus, putamen, and caudate, which composes the basal ganglia. (340) Increased gray matter density in the hypothalamus and decreased gray matter density in the prefrontal cortex have been reported in the IBS brain. (341) In rectal distention experiments, patients with IBS had a differential brain response in the pain matrix and default mode network. (342) IBS patients showed increased engagement of endogenous pain faciliatory pathways and decreased levels of the endogenous pain inhibitory mechanism in the brain regions associated with visceral afferent processing and emotional arousal, including the left dorsal anterior cingulate gyrus and the bilateral anterior insulae. (343) A meta-analysis of adult studies that evaluated brain response to rectal balloon distension by functional MRI (fMRI) reported differences between healthy control subjects and patients with IBS in these brain regions. (344) IBS patients with a history of abuse reported increased pain and anxiety with rectal distension accompanied by similar fMRI changes. (345) The stress and arousal circuit demonstrated in human subjects by fMRI shares significant homology with the stress circuit related to CRF–CRF1 receptor signaling in rodents, thereby potentially implicating the HPA axis as a facilitator of gut–brain axis communication. (346)
Recently, evidence for disrupted subcortical and cortical regions mediated by gut microbial modulation has been emerging in IBS. An association between brain region-to-region functional connectivity and microbiota has been reported. Labus et al. found a correlation between Clostridia and Bacteroidia with connectivity of the thalamus, the basal ganglia (caudate nucleus, putamen, pallidum, nucleus accumbens), the superior part of the precentral gyrus, the anterior insula, and the ventral prefrontal regions in IBS patients. (347) Recently, the same group also reported on fecal metabolites and resting state fMRI where the differences in histidine, cysteine, glycine, glutamate, spermidine, and anserine were significantly associated with the alteration in the left dorsal part of the posterior cingulate gyrus to the left putamen. Also, the changes in histidine, tryptophan, uracil, 2-deoxyuridine, thymidine, and succinate were differentially associated with the alteration in the right superior frontal gyrus to the right putamen. Interestingly, this interaction may be mediated by aberrant tryptophan signaling in IBS, which is important because it is a substrate for serotonin synthesis. (348)
Previous studies have compared brain differences between IBS-C and IBS-D. These studies have examined task states and have shown group-related differences in brain networks involved in integrating emotions [emotional arousal network, (EAN)], perception [sensorimotor network, (SMN); salience network, (SAL)], visceral functions [central autonomic network, (CAN)], and pain processing [default mode network, (DMN); central executive network, (CEN); SMN; SAL; EAN; and others). (349) Prior studies comparing IBS-C, IBS-D, and healthy controls (HCs) undergoing aversive rectal stimuli have identified abnormal connectivity in the SAL (350,351) and EAN (343,350) in IBS-C and in the occipital network (OCC) (351) in IBS-D. This may indicate a greater importance of alterations in sensory, emotional, and autonomic responses associated with the perception of visceral pain and discomfort in IBS-C. A recent study has tested the hypothesis that IBS-C exhibits bowel-habit-specific changes in the brain that reflect altered sensory and emotional regulation processing of visceral inputs from the “top-down,” while IBS-D would have widespread gut microbiome and metabolome changes (e.g., tryptophan, SCFAs), which may translate to “bottom-up” brain changes (e.g., SMN, DMN). (349) Indeed, in IBS-D, the study’s findings showed a correlation between high levels of gut metabolites tryptophan and phenylalanine and aberrant connectivity in brain regions involved in processing unpleasant visceral stimuli (SMN) and self-related thoughts (DMN). (349) These results suggest that increased tryptophan in the gut may lead to loosened stool, and tryptophan-related signaling may travel to the posterior insula and increase pain perception and emotional salience in IBS-D, thereby suggesting a “bottom-up” signaling direction. However, IBS-C’s microbiome and metabolome resembled HC, and the increased connectivity in the default mode (DMN) and salience (SAL) networks compared with IBS-D may indicate abnormalities in the emotional physiological processing of visceral signals. (349) IBS-C’s relatively isolated brain changes may indicate a more “top-down” mechanism to produce the constipation-predominant phenome. That study by Sarnoff et al. has shown a link between the chronicity of IBS symptoms, B. stercoris and F. prausnitzii, and brain connectivity in the caudate nuclei.
Thus, we might be in the mere beginning of understanding how alterations in gut microbiota may lead to the disruption of the intricate host–gut–microbiota interaction: is it a cause or a result of IBS pathology? In the past decade, much knowledge has been gained from clinical microbiota-altering interventions, such as the low-FODMAP diet and fecal microbiota transplantation (FMT), which have emerged as debatably successful treatment strategies. However, their effects on the gut microbiome–brain axis are still far from understood. It has been proposed that probiotic amelioration of IBS symptoms may be acting indirectly through an anti-inflammatory mechanism. (352) Such anti-inflammatory mechanisms may also be partially responsible for the positive effects of dietary restrictions, such as those seen in the low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet in IBS. (353−355) An alternate method for IBS treatment involves FMT from non-IBS individuals to patients with IBS. (356−359)
Functional Dyspepsia
Functional dyspepsia (FD) is a worldwide prevalent DGBI affecting 10%–30% of adults and 3.5%–27% of children worldwide. (360) The main clinical symptoms of patients are early satiety, postprandial discomfort, epigastric pain, epigastric distension, epigastric burning, loss of appetite, belching, nausea, and vomiting, which are often accompanied by anxiety and depression. (361) FD pathogenesis is linked to GI dysmotility, visceral hypersensitivity, impaired gastric tolerance, disrupted gastrointestinal mucosal integrity, abnormal function of the gut microbiome–brain axis, increased eosinophils in duodenum, dysbiosis, Helicobacter-pylori infection, postgastrointestinal infection, diet, genetics, and mental and psychological factors. (278)
An increasing number of studies have confirmed the close association between disturbance in the relative abundance and composition of the gastrointestinal microbiota and the occurrence and progression of FD. Actinomyces, Atopobium, Leptotrichia, Prevotella, and Veilonella counts differ between FD and control patients. (362) The finding was preceded by an observation that, in FD patients, gut barrier integrity is impaired and expressed as lowered transepithelial resistance; diminished expression of proteins of tight junctions; and lastly, elevated levels of mast cells, eosinophils, and interstitial lymphocytes. (363)
Surprisingly, FD patients not only had different gastrointestinal microbiota compared with non-FD, but also had different oral microbiota abundance and composition. Proteobacteria were the dominant bacteria in FD patients’ saliva, while Bacteroidetes were the dominant bacteria in healthy controls. The abundance of Spirochaetes in FD patients was higher than that in healthy controls, while the abundance of Fusobacteria, TM7, and Proteobacteria was lower than in healthy controls, and the levels of Kingella and Abiotrophia genus levels were also significantly different. (364)
Mental illness plays a significant role in the pathogenesis of FD. Anxiety at baseline has been shown to increase the risk of developing FD by almost 8 times after 10 years follow-up. (365) Interestingly, multiple studies highlighted that the prevalence of anxiety and depression is significantly increased in patients with FD compared with healthy people. Furthermore, pathophysiological research indicates that psychosocial factors and mental disorders may play a role in FD by modulating both visceral signal processing in the brain (366) and the effects of stress hormones on pain perception. (367) Furthermore, it is known that psychosocial factors and stress hormones also affect other aspects of the GI tract, such as motility, immune system activation, permeability, and microbiota.
However, FD symptoms are thought to induce anxiety or depression because of a cytokine response in low-grade intestinal inflammation, which plays an important role in the development of psychological distress in patients with FD. (368) A growing body of evidence suggests that the gut microbiota communicates with the central nervous system, possibly neuro-immuno-humoral pathways, thereby influencing brain function. (369) Furthermore, microbiota release neuroactive compounds, such as GABA, serotonin, dopamine, and acetylcholine, thereby acting locally on the enteric nervous system. Some of these neuroactive substances access the brain through the blood and the circumventricular organs or via the vagus nerve. Therefore, it could be hypothesized that a disturbed microbiome might affect mental health, followed by anxiety and depression. Thus, the mental disorders might be a consequence of the dysbiosis and, therefore, promote the development of FD, which may explain the findings that anxiety increases the risk of FD (365) and observations indicating that psychosocial factors and mental disorders may play a role in FD by modulating visceral signal processing in the brain. (366,370)
Functional Constipation
Functional constipation (FC) is a common DGBI with a global prevalence ranging approximately from 10.1 to 15.3% (371) and is characterized by difficult bowel movements and/or a sense of incomplete evacuation, thus influencing quality of life. (372) Previous studies showed that the gastrointestinal microbiota composition of constipation is clearly distinct from that of normal individuals. The species diversity of microbiota in the patient samples was lower than that in healthy subjects; it was also accompanied by significantly reduced levels of Bifidobacterium and Lactobacillus and an increased abundance of Desulfovibrionaceae. (373) Levels of butyrate-producing bacteria, such as Faecalibacterium and Roseburia, were significantly reduced in patients with FC. (373) It has also been confirmed that the relative abundance of methanogenic bacteria is increased in patients with slow transit constipation relative to healthy subjects. (373,374) In another study, Chen et al. collected 3056 fecal amplicon sequence data from five research cohorts and used machine-learning methods to construct the constipation discriminant model. The model identified 15 top-ranking biomarkers, particularly inflammation-related pathogenic bacterial genera Serratia, Dorea, and Aeromonas. (375) A recent shotgun metagenomics study confirmed the results of previous studies by showing that the relative abundance of Roseburia intestinalis, a prominent butyrate-producing bacterium, was reduced in patients with constipation in comparison with healthy controls, and the microbiome corresponding to constipation was enriched for pathways implicated in methanogenesis. (376) In contrast, the microbiome of healthy individuals was characterized by high levels of genes associated with carbohydrate, fatty acid, and lipid metabolism. (150)
Notably, different intestinal sites harbor certain gut microbiomes, yet the majority of recent research has focused on the analysis of fecal-derived microbiota, which are accessible via noninvasive sampling methods. However, luminal microbiota is generally considered to be representative of the distal large intestinal content. The mucosa-associated microbiota, which live in more intimate contact with the host, cannot be fully replicated by fecal microbiota. (377) In patients with constipation, there is even less similarity between fecal- and mucosa-associated microbiota compared with healthy controls and patients with diarrhea. (116) These differences may be due to drier stool allowing fewer signaling molecules to enter the mucosa (378) or the longer transit time providing more opportunities for the communities to diverge. (116) Hence, mucosa-associated microbiota are more likely to affect the host’s epithelial and mucosal function than luminal microbiota. (379) Comparative analyses between fecal and mucosal microbiota showed that the colonic mucosal microbiota composition was correlated with constipation (and was accompanied by a significant increase in Bacteroidetes), while the fecal microbial communities were correlated with colonic transit and methane production rather than constipation. (380) However, more evidence is needed to prove the relationship between the mucosal profile and constipation.
Slow gut transit has been associated with reduced fecal water content, higher fecal pH, higher microbial cell density and diversity, and a shift in microbial metabolism from saccharolysis toward proteolysis, as reflected by reduced levels of short-chain fatty acids and increased levels of branched-chain fatty acids (BCFA). (381) It is likely that once easily accessible carbohydrate sources become scarce in the colon, the gut microbes switch to ferment dietary and mucin-derived proteins. While saccharolysis by the gut microbiota gives rise to SCFA that are beneficial for the host and a source of energy for the colonocytes, proteolysis can lead to the accumulation of compounds such as BCFA, phenols, indoles, ammonium (NH3) and hydrogen sulfide (H2S) that are generally considered detrimental for health. Moreover, hydrogen (H2) with carbon dioxide (CO2) or formate can be converted into methane (CH4) by methanogenic archaea, which are also linked to slower transit time. In addition, the production and circulation of secondary bile acids and hydrolysis of host-derived glucuronides excreted via bile can also be affected by alterations in gut transit time. (381)
FC in patients would accompany mental disorders like anxiety and varying severity of depression. (382) Evidence from recent neuroimaging studies illustrated that FC patients had significant structural and functional alterations in brain regions that are involved in visceral sensorimotor, cognitive control, and emotional regulation, (383−389) thereby confirming its reclassification as DGBI. Among these altered brain regions in FC patients is the anterior insula, which is generally regarded as a critical node for its essential role in processing interoceptive signals, modulating visceral activities, and regulating emotions and cognitions. (383,385,389−391)
Stress and Stress Resilience
Chronic stress is rapidly becoming a global societal challenge. Stress constitutes a state of threatened homeostasis triggered by intrinsic or extrinsic adverse forces (stressors) and is counteracted by an intricate repertoire of physiological and behavioral responses aiming to maintain/reestablish the optimal body equilibrium (eustasis). Stress is a nonspecific response of the body to any demand imposed upon it that disrupts the body homeostasis and manifests with symptoms such as anxiety, depression, or even headache. (392) Stress can be hardly avoided in the present-day, modern, competitive life. Although eustress is important for people’s rapid reaction to threats, chronic stress is associated with detrimental effects on physical health and adverse implications on the immune, neuroendocrine, and central nervous systems. (392)
Acute stress activates the HPA axis, thereby resulting in an immediate release of cortisol. This response prepares the individual to defend against or escape from a threat. After the threat subsides, normal homeostasis should return. However, when that fails to occur, chronic activation of the stress response results in dysregulation of the HPA axis and an increased risk of subsequent diseases/disorders. (320) It also acts on the gut to increase the release of proinflammatory mediators, which leads to increased gut permeability. (393) Repeated exposure to stress can initiate a vicious cycle of low-grade inflammation and negatively impacts the intestinal barrier and immune signaling within the gut. (394,395)
A link between stress and the abundance of lactobacilli in mice was discovered for the first time more than 40 years ago. (396) Several preclinical studies have documented that stress impacts gut microbial composition in a number of different hosts using different stress models ranging from water avoidance to maternal separation, heat, and acoustic stress and overcrowding. (320) These results have shown clinical relevance and translated into human studies, thereby showing the influence of stress on gut microbiota and gut microbiota on stress modulation through different stressors, such as surgical intervention, academic examination, or military training, among others. (397−400)
Maternal stress during pregnancy displays a distinct fecal microbiota profile, which has generational consequences. The maternal microbiota influences offspring microbiota and correlates with hyper-reactivity of the HPA axis, together with other perinatal factors, as a key determinant of offspring outcomes. These findings have been confirmed in humans in a population-based study whereby infants born to mothers with high cumulative stress during pregnancy exhibited an aberrant microbial composition. (401)
The effects of early life stress on the microbiota may extend to adulthood. (49) It is, therefore, plausible that changes in the gut microbiota due to stress at least partially mediate the onset of stress-related depressive or anxious episodes. Correlational studies have shown that fecal microbiota composition in individuals with anxiety or depression differs from that in healthy controls. (202,402,403) Women with a higher fecal Prevotella abundance experienced increased negative emotional response to viewing negative images and lower brain activity in the hippocampus than those with a higher Bacteroides abundance. (404)
Stress resilience is the ability to experience stressful events without the development of chronic elevated stress (psychological and/or biological) and associated changes in emotional behavior. (405,406) Stress susceptibility is related to psychological factors, such as passive coping skills and high emotional reactivity, but is also associated with biological factors such as hypo- or hyper-responsiveness of the stress response system, sex hormones, central and peripheral immune activation, and glucocorticoid resistance. (407) The gut microbiome is a biological factor that is emerging as a possible influencer of stress resilience. The broad influence of the gut microbiota on human health, including psychiatric health, has begun to be realized and understood over the past decade. Preclinical studies have reinforced this principle showing a connection between the gut microbiome–brain axis and stress resilience. Li et al. recently reported that certain mice exposed to chronic stress were found to be resilient to stress-induced corticosterone and anxiety-like behavior. These mice contained a relative abundance of Lactobacillus species within their gut microbiome. Subsequent stress-susceptible mice saw decreased anxiety-like behavior and corticosterone levels with Lactobacillus murinus supplementation. (408)
Modulation of the gut microbiome has emerged as a possible way to improve stress resilience and mental health. In 2013, Dinan et al. coined the term psychobiotics, which refers to live microorganisms when ingested in adequate amounts that produce a health benefit in patients suffering from psychiatric illness; the definition has been expanded to include other interventions that modulate the gut microbiome, such as prebiotic. (409) The term psychobiotics has since been widely adopted by neuroscientists conducting research on neurodegenerative diseases and depressive disorders in order to describe the use of different biotics to tackle depression, stress, anxiety, and other mental health complaints through the GBA.
Sleep
Adequate sleep quality and sufficient duration are necessary to support both mental and physical health and overall quality of life. (410) Inadequate sleep in either duration and/or quality has been increasingly recognized as a global public health issue. Sleep disturbances are typically characterized by a decrease in one’s ability to initiate and maintain sleep and by a reduced proportion of the deeper, more restorative sleep. (411) Increased risk of developing chronic diseases, such as obesity, type 2 diabetes, heart disease, some types of cancer and mental illness, has been associated with inadequate sleep. (411,412)
Evolving evidence has shown the impact of gut microbiota on sleep. In humans, previous research has shown that partial sleep deprivation can alter the gut microbiome composition in as little as 48 h; (413) however, longer periods of sleep deprivation apparently do not have this effect. (414) A more recent study showed that high sleep quality was associated with a gut microbiome containing a high proportion of bacteria from the Verrucomicrobia and Lentisphaerae phyla and that this was associated with improved performance on cognitive tasks. (415)
Microbiome diversity was positively correlated with sleep efficiency and total sleep time and was negatively correlated with the sleep fragmentation, thereby indicating that diversity of the gut microbiome promotes healthier sleep. However, two previous studies in humans suggested that microbiome diversity is insignificantly affected following a period of sleep restriction. (413,414) A critical difference between these studies is that the former study measured sleep over an extended period of time (one month), while the latter two studies manipulated sleep by experimentally restricting sleep. Accordingly, it is possible that short-term manipulations to sleep do not influence the gut microbiome diversity, but rather that microbiome diversity can influence sleep in the long term.
Gut microbiota may affect sleep status via degradation products, such as muramyl peptides (MPs), lipopolysaccharide, and melatonin. (416) These degradation products could activate immune cells that lead to the release of cytokines, which could affect sleep. Cytokines represent a potential critical interface between sleep physiology and gut microbiome composition. The acute phase pathway, cytokines IL-1β and IL-6, in particular, are strongly associated with sleep physiology. IL-1β is a major somnogenic factor. (416) IL-1β administration in human and nonhuman animals increases spontaneous sleep and fatigue, and IL-1β increases with ongoing sleep loss. (416) Unlike IL-1β, IL-6 is not a direct somnogenic factor, but sleep loss results in increased IL-6 levels. (417) In the gut, IL-6 and IL-1β-mediated inflammation fluctuates in response to stress and disease. (418) For example, intestinal mucositis results in an increased expression of IL-6 and-IL-1β in the small intestine (419) and in serum and colon tissue (420) in mice. In humans, chronic stress, alone, increases IL-6 and-IL-1β.
Alterations in the microbiome have been shown to influence neurotransmission of serotonin in both the peripheral and central nervous system. (411) While this may convey a positive impact on mood and psychological well-being, (421) it also has the potential to influence sleep (422) as serotonin is acetylated and, then, methylated to yield melatonin─the hormone important in helping regulate sleep/wake cycles. (423)
A recent meta-analysis involving 36 studies showed that sleep disorders were common in IBS, and the prevalence rate was 37.6% (95% confidence interval: 31.4% to 44.3%). (424) The pooled odd ratio revealed that sleep disorders were significantly associated with IBS. The reason why sleep disorders are associated with IBS remains unclear; however, the gut microbiome–brain axis could play an important role in the pathogenesis of both. Modification of the autonomic nervous system activity has been observed in cases of sleep deprivation, which indicates that sleep disorder might be associated with autonomic dysregulation. (425,426) It has been postulated that sleep inhibits the HPA axis, and sleep disorder may result in a 24 h increased secretion of cortisol. (427) Moreover, IBS symptoms, such as abdominal pain, may activate the sympathetic nervous system and, hence, reduce sleep efficiency. (428) Microbiome modulation has been shown to influence melatonin production and modulate IBS symptoms in individuals with a normal circadian rhythm. (429) Overall, although the reason for sleep disorders seen commonly among IBS patients is obscure, a gut microbiome–brain axis disorder may underlie this association. (427)
An additional layer of evidence has been shown by the intertwined interactions between the gut microbiome and the central and peripheral circadian rhythms. (430) The disruption of the host circadian rhythm alters the gut microbiome equilibrium. In addition, the microbiome is able to mediate host clock gene expression in peripheral organs and the suprachiasmatic nucleus.
Intestinal bacteria have shown inherent circadian rhythms, as shown in previous metagenomic studies. (430) Diurnal fluctuations in abundance and activity have been observed in Clostridiales, Lactobacillales, and Bacteroidales, which account for ∼60% of the microbiota. (431) Studies on human stool samples of Enterobacter aerogenes have demonstrated responsivity to the circadian hormone melatonin, as well as a daily rhythm. (432) The gut epithelium experiences differential bacterial species and metabolites depending on the time of day and expresses toll-like receptors that sense microbiotal metabolites in a rhythmic pattern. (433) It has been proposed that the gut microbiome influences the rhythmic expression of the host’s internal clock by signaling molecules, such as butyrate, and by oscillations in microbiotal bacterial content in response to feeding patterns. (434)
Cognitive Function
Abundant evidence supporting the role of the gut microbiota in modulating cognitive function is mostly based on animal research. However, few studies have examined the influence of gut microbes on human cognition and supported the clinical relevance. One of these studies showed that the gut microbiota composition of obese and nonobese subjects was linked with scores in speed, attention, and cognitive flexibility coupled with alterations in neural activity in the thalamus, hypothalamus, and amygdala, thereby suggesting that obesity affects the microbiota composition and subsequent cognitive performance. (435) Additionally, the microbiota composition in 1-year-old babies was associated with cognitive development. Three groups of microbial composition have been identified where better performance was seen in the group with higher levels of Bacteroides. (436) This group was also less likely to be born via C-section, which supports the previous observation linking delivery mode with child cognitive development, (437) thereby highlighting the importance of gut microbiota colonization in cognitive development and function. (436)
Microbiome modulation has demonstrated beneficial effects on cognitive performance. Lactobacillus strains have improved cognitive performance in healthy elderly subjects. (438) Fermented milk product supplemented with a probiotic has been shown to modulate the activity of brain regions involved in cognitive performance during an emotional attention test in healthy women. (439) Also, the modulation of the microbiome via inulin prebiotic has been shown to improve memory and mood in healthy individuals. (440)
These results taken together indicate the potential role of the gut microbiome–brain axis in regulating cognitive performance and that microbiome modulation could be a promising approach for improving cognitive function in both healthy and vulnerable individuals. However, much more work is needed to understand why specific microbiome-related interventions have the potential to modulate cognition.
Emotional Well-being
Gut microbiota is emerging as a key mechanism for modulating emotional well-being. (441) In fact, emotional disorders, such as depression and anxiety, are frequently accompanied by functional gastrointestinal disorders, which suggests an association between gut function and psychiatric diseases. (442,443) Recent research reveals the gut–brain axis association with the vagus nerve plays an important role in emotional well-being. The subdiaphragmatic vagus nerve is a major modulatory pathway between the brain and gut microbiota. (444) Data suggest that fecal microbiota from depressed mice produce depression-like phenotypes and abnormal gut microbiome composition when transplanted to nondepressed mice via the subdiaphragmatic vagus nerve. (445)
Gut microbiota is emerging as a key mechanism for the modulation of emotional well-being. (441) In fact, emotional disorders, such as depression and anxiety, are frequently accompanied by functional gastrointestinal disorders, which suggests an association between gut function and psychiatric diseases. (442,443) Findings from a longitudinal study further suggest that intestinal infections significantly predict the future onset of anxiety disorder. (446)
Evolving clinical evidence indicates the significant links between the gut and emotion; for example, altered gut microbiota composition (447) was reported in patients with depressive disorder in terms of fecal microbial diversity, as well as the level of the genus Faecalibacterium. (403) In healthy adults, self-rated higher quality of life and favorable personality types (high in openness and conscientiousness) were associated with the composition of certain gut microbiota (i.e., Faecalibacterium, Coprococcus, and Lachnospiraceae), as well as an enriched diversity of the gut microbiota community. (448,449)
Recent studies suggest that enterotypes play a role in regulating the association between the gut microbiome and mental health. (404,449) Enterotypes refer to robust stratified clusters on the basis of the variation found in the levels of one of three genera in the gut: Bacteroides (enterotype 1), Prevotella (enterotype 2), and Ruminococcus (enterotype 3). (450) Individuals’ enterotype cluster depends on, in part, long-term diet─i.e., the amount of ingested animal protein/saturated fats (Bacteroides-type) versus carbohydrates/simple sugars (Prevotella-type)─whereas they are less influenced by the hosts’ body mass, age, and sex. (450−452)
A recent brain imaging study found distinct patterns of the emotional process and brain connectivity between stratified enterotypes; clusters with a greater abundance of Prevotella show higher levels of emotional response, along with prominence in the connectivity of emotional, attentional, and sensory-processing brain regions when compared with Bacteroides-dominant clusters. (404) A large-scale microbiome study also revealed that the Bacteroides-enriched enterotype is significantly associated with a lower score on the subjective feeling of quality of life, as well as a higher score regarding depressive symptoms.
A recent exploratory study revealed that gut microbiome diversity is related to emotional well-being and that enterotypes significantly moderate the links between emotional well-being and gut microbiome diversity. (441) The enterotypes did not alter mood status, itself, but moderated the strength of the association between one’s mood and gut microbiome diversity. In the Prevotella-dominant group, emotional status was more closely related to gut microbiota diversity, such that a positive effect was associated with increased gut microbiota diversity. However, in the Bacteroides-dominant group, one’s mood status was not significantly associated with gut microbiome diversity. This finding is in line with the results of Tillisch et al. (404) in that only the high-Prevotella group displayed an increased response to affective images in the limbic system. Such findings suggest a significantly tighter connection between emotional well-being and the well-being of the gut microbiota community, particularly in the Prevotella-dominant condition.
There is an evolving body of evidence suggesting that the modulation of the gut microbiome by biotics administration or via food supplements (i.e., psychobiotics) may closely affect one’s mood. Benton et al. (421) showed that the consumption of probiotic-containing yogurt improved the self-reported mood of those whose mood was initially poor. Messaoudi et al. (176) showed that consumption of the probiotics reduced anxiety and depression scores in subjects with reduced urinary free cortisol. Also, consumption of Lactobacillus helveticas and Bifidobacterium longum reduced somatization, depression, anger and hostility, hospital anxiety, depression-scale global scores, and self-blame scores on coping checklists and increased focus on problem solving, but there was no effect on perceived stress. (176) Moreover, the administration of a combination of Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum for 8 weeks improved the depression score. (453) In a 2017 systematic review by Wallace and Milev of 10 clinical trials, most of the studies found positive results on measures of depressive symptoms. (454) A recent meta-analysis (455) included 30 randomized placebo-controlled studies and revealed that most probiotics did not affect mood, anxiety, depression, and psychiatric distress when compared with placebo at the qualitative questionnaire level; however, on the quantitative meta-analysis level, probiotics intervention showed slightly significant effect compared with placebo. In addition, EEG and imaging studies summarized in a recent review proved that probiotics are able to exert effects on CNS function in humans; although, the number of studies is still low. (455)
Overall, there is emerging evidence on the link between one’s emotional status and gut microbiome diversity and composition. The current evidence suggests that emotional well-being and the feeling of happiness can be associated with gut microbiota profiles in healthy adults, especially when stratified by enterotype. The enterotype-specific links between emotional well-being and gut microbiome diversity suggest that enterotypes may work as an individually tailored intervention. With the expanding interest in the role of the gut microbiome–brain axis in mental health, this nascent field still needs to build up empirical evidence to fill the gap in our understanding of how gut microbiota communicates with the brain to affect emotional well-being and the feeling of happiness.
Prebiotics, Probiotics, Synbiotics, Postbiotics, and Psychobiotics
Probiotics
Probiotics are defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. (93,456) Probiotics usually comprise bacteria, including, among others, Lactobacillus, Bifidobacterium, and Bacillus, although a few strains of the yeast Saccharomyces have also been included in probiotic cultures. Probiotic microorganisms must have several features, including a demonstrated benefit to the host and the recognition that they are safe for human consumption, i.e., they have generally been recognized as a safe designation. They are resistant to acid and bile salts that are encountered in the GI tract. The ability to adhere to the intestinal epithelium is a useful trait that promotes both the persistence of the probiotic and host interactions. Other useful features are that they are easily cultured and are resistant to drying, freezing, and freeze-drying so that the probiotic may be produced and stored in bulk. Probiotics can enhance immune function, promote fiber assimilation for SCFA production, and help suppress pathogens in the GI tract. (93,457,458)
Prebiotics
Prebiotics are defined by ISAPP as a substrate that is selectively utilized by host microorganisms conferring a health benefit. (31,93) Therefore, such a definition expands beyond the classical prebiotics composed of polysaccharide carbohydrates and could include any other nondigestible microbiome-fermentable ingredients, such as herbal secondary metabolites and flavobiotics. The definition stresses that the effects must be microbiota-mediated and that the beneficial health effects must be documented for a substance to be considered a prebiotic. (459) The most well-known products of microbiome-derived fermentation are SCFAs, such as butyric acid, acetic acid, or propionic acid, which have a beneficial effect on the host. Moreover, prebiotics modulate lipid metabolism, increase calcium absorption, have a positive effect on the immune system, and reduce the risk of broad diseases. (458)
Synbiotics
ISAPP defined synbiotic as a mixture comprising live microorganisms and substrate(s) selectively used by host microorganisms that confer a health benefit on the host. The panel concluded that defining synbiotics as simply mixtures of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. The ISAPP panel differentiated synbiotics into two groups: complementary synbiotics and synergistic synbiotics. A complementary synbiotic that has not been designed so that its component parts function cooperatively must be composed of a probiotic plus a prebiotic. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the coadministered microorganisms. (460)
Postbiotics
Postbiotics are a class of products that has emerged in the last 10 years. Postbiotics are defined by the ISAPP as preparations of inanimate microorganisms and/or their components that confer a health benefit on the host. Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. (458,461) Postbiotics, because they are derived from probiotic microorganisms, have many of the same benefits as probiotics. The effects of postbiotics are often more reliable and predictable than probiotics. Postbiotics tend to have a longer shelf life than probiotics and they are more target-specific and safer in terms of their interaction with the human GI tract. (93)
Psychobiotics
The term psychobiotic was coined to describe bacteria that confer mental health benefits. Psychobiotics have demonstrated the ability to improve mood, reduce anxiety, and enhance cognitive function in both healthy populations and patient groups. While the term psychobiotics originally referred to beneficial live organisms, such as bacteria that are specifically beneficial for mental health, (409) the definition has been expanded in recent years to include prebiotics whose effect on the brain is bacteria-mediated. (462) It is also worthwhile considering a wider definition of psychobiotics to include any substance that exerts a microbiome-mediated psychological effect or at least possesses psychobiotic properties, such as probiotics, prebiotics, synbiotics, and postbiotics. (462,463) Recently a new term “phyto-psychobiotics” has been coined to describe medicinal plants whose mental effects are mediated via gut microbiota modulation by prebiotic-like effects, postbiotic-like effects mediated by the active secondary metabolites produced by the gut microbiome from the nondigestible herbal ingredients, or even by antibiotic-like effects as in the case with some medicinal herbs that have a mental impact by reducing the level of pathogenic bacteria. (464)
Pre-, Pro-, Postbiotics, and Fecal Microbiota Transplantation in the Development Pipelines
A search of the CAS Content Collection (84) reveals the top organizations for research and journal publications related to the gut microbiome and mental and digestive health. All these top players are universities and research institutes, and the University College Cork, the Chinese Academy of Science, the University of California, and McMaster University lead the field (Figure 14A). The lead universities and medical centers related to patenting activity for the gut microbiome in mental and gut health include the University of California, Johns Hopkins University, and the University of Texas (Figure 14B).
Figure 14
Figure 14. Top universities, research institutes, and hospitals publications (1967–2022) related to gut microbiome research in mental and gastrointestinal health: (A) journal publications and (B) patents.
Private Investment
Researching the overall global private investment activities of the microbiome field provides insight into the commercial interest into this area. Performing a search of prebiotics, probiotics, and the microbiome within PitchBook, an online source for investment data, reveals the overall venture capital activities. The search revealed that both capital raised and deal counts from venture capital investment are rising within this industry. (465) From 2014 through 2018, the total capital raised increased from $250 million to over $1 billion. Deal counts followed the same pattern from 2014 to 2018 and increased from 25 to 125. The number of deal counts in 2019 further increased; however, the overall capital raised fell to just under $900 million. Deal counts continued to rise for 2020 and 2021, along with capital raised, which totaled over $2.1 billion, while 2022 ended with a slight decrease in total venture capital investment (Figure 15). The venture capital investment data in this area clearly shows a recent and increasing commercial interest surrounding prebiotics, probiotics, and the microbiome, thereby revealing its potential promise for therapeutic applications.
Figure 15
Figure 15. Overall capital raised and deal counts of venture capital investment for the prebiotic, probiotic, and the microbiome field ($) (source: pitchbook.com).
Companies and Academic Institutions Investigating Treatment of Mental Disorders and DGBI through Gut Microbiome Modulation
With the GBA being a bidirectional communication network, we herein examine a highlighted selection of global companies and academic institutions researching and producing prebiotics, probiotics, postbiotics, and utilizing fecal microbiota transplantation to treat a variety of consumer health-related mental disorders and DGBI. This global analysis of worldwide companies and academic institutions, while extensive, is not comprehensive and provides insight into both the present and future state of the field.
Probiotics
Companies, along with universities and health institutions, are utilizing probiotics for the treatment of mental disorders at slightly different rates (Figure 16). Companies are focusing more on stress than universities and medical institutions, with all organizations researching anxiety at about the same rate. Universities and medical institutions are researching depression, cognition impairment, and sleep disorders at a higher rate than industry. With universities and medical institutions on the forefront of research, this shows the up-and-coming possibilities for probiotic products for the treatment of depression, cognition impairment, and sleep disorders being produced for consumers in the future. Research in the area of utilizing probiotics for DGBI is much more extensive and historically established (Supplemental Table 1) than mental health disorders (Figure 16). Companies, universities, and medical institutions research most DGBI at a similar rate, with universities and medical institutions having a higher focus on IBS. IBS is more prevalent among those who eat a Western diet. With more of the world’s population adopting a Western diet, the prevalence of IBS is expected to increase. (466) The research among universities and medical institutions is shadowing this trend as researchers evaluate probiotic treatment options for this DGBI increasing in prevalence (Figure 16).
Figure 16
Figure 16. (Left) The percentage and number of analyzed global organizations utilizing probiotics for mental disorders and DGBI treatment. (Right) The percentage and number of analyzed global organizations utilizing prebiotics for mental disorders and DGBI treatment.
Prebiotics
Fewer organizations are researching prebiotics for the treatment of mental disorders and DGBI when compared with probiotics (Figure 16). Prebiotics for DGBI are researched more than mental disorders, with more focus on IBS and functional constipation (Figure 16). This field has many future growth opportunities for both industry and research as it grows and becomes established. Similar to the number of organizations, the number of documents in the CAS Content Collections related to prebiotics is about three times lower compared with those related to probiotics. However, the growth rate in the prebiotics research has increased in the last two years.
Postbiotics
Postbiotics are the least researched therapeutic examined and are mainly limited to a small commercial presence (Figure 16). With such a small commercial and research presence, the opportunities are also abundant for postbiotic therapeutics.
Fecal Microbiota Transplantation
FMT research is found to be rare in comparison with other microbiome modulation strategies in mental disorders and newly established with only a very small number of companies and universities participating in this field (Figure 17). Most of the FMT research in DGBI focuses on IBS treatment (Figure 17). This field is currently showing clinical scientific evidence for the successful treatment of the serious and sometimes deadly condition of Clostridium difficile (C. Diff) infection. (467) Recently, Australia’s Therapeutic Goods Administration gave the world’s first regulatory approval to company BiomeBank for its biologic microbiome product called Biomictra for the treatment of C. Diff infection. (468) The US FDA followed a few weeks later with its official approval for the biologic drug consisting of live human-derived fecal microbiota, RBX2600 (Rebyota), produced by Ferring Pharmaceuticals, which is also for the treatment of C. Diff infection. (469) These first regulatory approvals open this method to endless opportunities for the treatment of many different diseases, and more studies are needed to prove its safety and efficacy.
Figure 17
Figure 17. (Left) The percentage and number of analyzed global organizations utilizing postbiotics for mental disorders and DGBI treatment. (Right) The percentage and number of analyzed global organizations utilizing fecal transplant for mental disorders and DGBI treatment.
Clinical Trials Landscape for Probiotics in Mental Disorders and DGBI
When examining clinical trials utilizing probiotics for the treatment of the mental disorders discussed within, there are currently a total of 52 clinical trials covering all stages between 2004 and 2022 listed on the US NIH clinical trials website. (470) The most studied mental health disorders are stress, followed by depression, anxiety, cognition impairment, and sleep disorders. Clinical trials utilizing probiotics for the treatment of DGBI are the most prolific and historically studied with 174 clinical trials. (470) The most studied DGBI are IBS followed by functional constipation, functional diarrhea, and functional dyspepsia.
The most researched probiotics for the treatment of mental disorders are the Lactobacillus species and a combination of Lactobacillus and Bifidobacterium species (Supplemental Table 1). For DGBI, the most widely used probiotic is the Lactobacillus species followed by the Bifidobacterium species, a combination of Lactobacillus and Bifidobacterium species, and finally the Saccharomyces species (471) (Supplemental Table 1).
Highlighted clinical trials examining probiotics as a treatment option for mental disorders and DGBI are explored in Tables 4 and 5. A select few are also examined in further detail below to showcase a variety of interventions and targeted conditions in clinical development, along with their status. While experimental data in this area is showing promising results, there are still conflicting results being reported.
Table 4. Highlighted Clinical Trials Utilizing Probiotics for the Treatment of Mental Health Disorders
| clinical trial identifier | condition | intervention | status |
|---|---|---|---|
| NCT05564767 (472) | depression, anxiety, stress | Bifidobacterium adolescentis Bif-038, Lacticaseibacillus rhamnosus LGG, Bifidobacterium BB-12 | recruiting |
| NCT03494725 (477) | stress, anxiety | Lacticaseibacillus paracasei Lpc-37 | complete |
| NCT04767997 (474) | sleep disorder | undisclosed probiotic formulation | recruiting |
| NCT03601559 (478) | cognitive impairment | Lactobacillus paracasei Lpc-37 | complete |
| NCT03615651 (479) | stress, cognition impairment | Lactobacillus helveticus, Bifidobacterium longum, Lactiplantibacillus plantarum | complete |
| NCT05567653 (473) | stress | Lactobacillus helveticus Rosell-52, Bifidobacterium longum Rosell-175 | recruiting |
| NCT03370458 (480) | stress | Lactobacillus plantarum DR7 | complete |
Table 5. Highlighted Clinical Trials Utilizing Probiotics for the Treatment of DGBI
| clinical trial identifier | condition | probiotic intervention | status |
|---|---|---|---|
| NCT02592200 (485) | functional constipation | Lactobacillus gasseri DSM 27123 | complete |
| NCT04304170 (486) | functional constipation | Bifidobacterium animalis lactis (LMG P-28145) | complete |
| NCT04662957 (487) | diarrhea-predominant irritable bowel syndrome | Bifidobacterium breve BB010, Bifidobacterium longum BL020, Bifidobacterium bifidum BF030, Bifidobacterium lactis BL040, Lactobacillus rhamnosus LR110, Lactobacillus paracasei LPC100, Lactobacillus acidophilus LA120, Lactobacillus casei LC130, Lactobacillus plantarum LP140, Streptococcus thermophilus ST25 | complete |
| NCT05566171 (488) | functional constipation | Bifidobacterium lactis CNCM I-2494, Bifidobacterium lactis DN 173-010 | enrolling by invitation |
| NCT01463293 (489) | functional constipation | Bifidobacterium lactis HN019 | complete |
| NCT01102036 (490) | functional constipation | Lactobacillus paracasei F19, Lactobacillus paracasei LA-5, Bifidobacterium lactis BB-12 | complete |
| NCT03721107 (491) | diarrhea- and constipation-predominant irritable bowel syndrome | Blautia hydrogenotrophica | complete |
| NCT00534170 (492) | functional diarrhea | Lactobacillus casei Shirota, Bifidobacterium breve Yakult | complete |
| NCT00794924 (493) | functional diarrhea, functional constipation | Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. bulgaricus | complete |
| NCT02213172 (494) | irritable bowel syndrome | Bifidobacterium longum R0175, Lactobacillus paracasei HA-196 | complete |
| NCT00807326 (495) | functional diarrhea | Saccharomyces boulardii | complete |
| NCT05054309 (496) | irritable bowel syndrome | Bifidobacterium longum NCC3001 | recruiting |
| NCT01099696 (497) | functional dyspepsia | Bifidobacterium infantis 35624 | complete |
| NCT01887834 (498) | irritable bowel syndrome | Lactobacillus gasseri, Bifidobacterium bifidum, Bifidobacterium longum | complete |
| NCT04605783 (499) | functional diarrhea | Saccharomyces boulardii CNCM I-745 | not yet recruiting |
| NCT04950296 (500) | irritable bowel syndrome with diarrhea | Lactobacillus plantarum UALp-05 | complete |
| NCT05149599 (501) | irritable bowel syndrome | Saccharomyces cerevisiae | complete |
Mental Disorders
Clinical trial number NCT05564767 is currently recruiting participants to assess the treatment of depression and anxiety in adults by utilizing probiotics Bifidobacterium alone and Lacticaseibacillus combined with Bifidobacterium. (472) Clinical trial number NCT05567653 is also recruiting for its study researching the treatment of stress in dancers with a probiotic product combination including Lactobacillus and Bifidobacterium. (473) Another study (NCT04767997) looking at the effects of probiotics on sleep disorders is also currently recruiting subjects. (474) Clinical trial number NCT03615651 researched the effect of a probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum, and Lactiplantibacillus plantarum on subjects’ functional brain responses during an emotionally stressful attention task. (472) Their findings showed a positive effect on brain responses in regions implicated in emotional and cognition processing, which supports the growing evidence that probiotics can help positively influence emotional regulation and brain function. (475) Another study (NCT04767997) that is looking at the effects of probiotics on sleep disorders is also currently recruiting subjects. Finally, a recently completed study (NCT03494725) found that supplementation with probiotic Lacticaseibacillus paracasei Lpc-37 significantly reduced perceived stress and anxiety in study participants. (476)
DGBI
Clinical trial number NCT05566171 is currently recruiting participants to research the treatment of functional constipation with two Bifidobacterium strains. Bifidobacterium was also researched in clinical trial number NCT04304170 and NCT01463293 for the treatment of functional constipation. Lactobaccillus and a combination of Bifidobacterium species and Lactobacillus were also researched for the treatment of functional constipation in completed clinical trials NCT01102036 and NCT02592200, respectively. Utilizing a combination of Streptococcus, Bifidobacterium, and Lactobacillus species, clinical trial number NCT00794924 researched the treatment of functional constipation and diarrhea in elderly hospitalized patients. The study showed positive results with the probiotics reducing days patients suffered from diarrhea or received laxatives, thereby displaying a positive effect on bowel movements. With diarrhea remaining a major public health concern in developing countries, study NCT00534170 researched the use of a probiotic drink containing both Lactobacillus and Bifidobacterium species for the treatment of diarrhea in young children. The study revealed the ingestion of a daily probiotic drink could prevent diarrhea in young children in a community setting within a developing country. (481) Another study (NCT00807326) also researched the treatment of functional diarrhea. They compared the treatment results of antigas/antidiarrheal drug combination loperamide/simeticone and probiotic yeast Saccharomyces boulardii. They discovered that while the probiotic did help alleviate symptoms, it was inferior to loperamide/simeticone. (482) Clinical trial number NCT01099696 also had discouraging results researching the treatment of functional dyspepsia with probiotic Bifidobacterium infantis 35624. While previous studies showed promise in patients with IBS, Bifidobacterium infantis 35624 did not show significant improvement in symptoms of abdominal discomfort and bloating in that study’s participants. Finally, a study (NCT04662957) researching a multistrain probiotic mixture of four Bifidobacterium, five Lactobacillus, and one Streptococcus species concluded its probiotic could offer benefits for patients with diarrhea-predominant IBS. (483) Another study (NCT03721107) showed more positive results for the treatment of both diarrhea and constipation-predominant IBS. Patients reported improvement in bowel symptoms and pain with the use of Blautia hydrogenotrophica. (484)
Clinical Trials Landscape for Prebiotics in Mental Disorders and DGBI
When examining clinical trials utilizing prebiotics for treatment of the mental disorders discussed within, there are currently a total of 15 clinical trials. (470) The most studied mental health disorder is stress, followed by anxiety, depression, sleep disorders, and cognition impairment. (470) A total of 50 clinical trials utilize prebiotics for the treatment of DGBI. (470) Similar to probiotics, the most studied DGBI using prebiotics is IBS, followed by functional constipation, functional diarrhea, and functional dyspepsia. (470) The most commonly used prebiotic in clinical trials is galacto-oligosaccharides (GOS), followed by other sugars such as fructan, glucan, and dextrose, along with various fibers.
Highlighted clinical trials examining the treatment of mental disorders and DGBI with prebiotics are explored in Tables 6 and 7. A select few are also examined in further detail below to showcase the variety of interventions and targeted conditions, along with their status in clinical development. The use of prebiotics for the relief of mental and gastrointestinal disorder symptoms is producing promising results.
Table 6. Highlighted Clinical Trials Utilizing Prebiotics for the Treatment of Mental Health Disorders
| clinical trial identifier | condition | intervention | status |
|---|---|---|---|
| NCT05372601 (504) | stress | GOS | complete |
| NCT05239845 (505) | sleep disorder | polydextrose, GOS | recruiting |
| NCT04324749 (506) | cognitive impairment, stress | roasted peanuts, peanut butter | complete |
| NCT05528575 (507) | stress | GOS, inulin, resistant potato starch RS2 | active |
| NCT04616937 (508) | anxiety, cognitive impairment | GOS | complete |
Table 7. Highlighted Clinical Trials Utilizing Prebiotics for the Treatment of DGBI
| clinical trial identifier | condition | intervention | status |
|---|---|---|---|
| ISRCTN54052375 (512) | irritable bowel syndrome | GOS | complete |
| NCT04491734 (513) | gastresophageal reflux | maltosyl-isomaltooligosaccharides (MIMO) | complete |
| NCT05207618 (514) | irritable bowel syndrome with diarrhea | chestnut and quebracho tannin extract | complete |
| ACTRN12612001270808 (510) | functional constipation | green kiwi prebiotic, gold kiwi prebiotic | complete |
| NCT05340712 (515) | functional constipation | infant formula with lactose (prebiotic) along with probiotics | recruiting |
Mental Disorders
Clinical study NCT04616937 researches the use of GOS for the treatment of anxiety by altering the gut microbiota. GOS increases probiotic bacteria Bifidobacterium abundance in the gut microbiome. The study reports that the supplementation of GOS may improve signs of anxiety and cognition impairment with an increase of reported attention. (502) Another recent study (NCT04324749) researched the prebiotic effect of peanut and peanut butter consumption on the cognitive and stress response of college students. The peanut prebiotic fiber and polyphenol content appears to enhance memory function and reduce stress because of the presence of both short-chain and very long-chain saturated fatty acids for healthy young subjects. (503)
DGBI
A published case study from 2019 showed a new observation that some patients taking a specific prebiotic soluble fiber, maltosyl-isomaltooligosaccharide (MIMO), had their gastroesophageal reflux symptoms resolve. (509) Clinical trial NCT04491734 followed about a year later to research this effect. The prebiotic MIMO reduced the severity and frequency of gastroesophageal reflux symptoms and improved the quality of life for participants. Clinical study ACTRN12612001270808 researched the use of a green kiwi prebiotic (inulin) and a gold kiwi prebiotic to treat functional constipation. The study showed a successful increase in bowel movements and also revealed that green kiwi prebiotic (inulin) supports the increase of two probiotic bacteria, Bifidobacteria and Lactobacillus, within the gut microbiome. (510) Another research study shows that gold kiwi prebiotic increased the abundance of Faecalibacterium prausnitzii within the gut microbiome, as well. (511) F. prausnitzii is a butyrate producer and displays anti-inflammatory effects. (511) When prebiotic GOS was tested in a clinical trial (ISRCTN54052375), it increased the probiotic bacteria Bifidobacteria within the gut. This helped alleviate symptoms of IBS, thereby showing that GOS is a potential therapeutic agent for this disorder. (512)
Clinical Trials Landscape for Postbiotics and FMT in Mental Disorders and DGBI
Postbiotic and FMT are the least researched among all clinical trials explored. When examining clinical trials utilizing postbiotics for the treatment of mental disorders, anxiety is the only disorder studied (Supplemental Table 1). Clinical trials utilizing postbiotics for the treatment of DGBI focus on IBS. (470) Only three clinical trials are researching FMT for the mental health disorders of depression, anxiety, and sleep disorders. Fecal microbiota transplants researching DGBI is higher with 27 trials researching both IBS and constipation.
Highlighted clinical trials examining the treatment of mental disorders and DGBI with postbiotics and FMT are explored in Tables 8 and 9. A select few are also examined in further detail below to showcase a variety of interventions and targeted conditions, along with their status in clinical development.
Table 8. Highlighted Clinical Trials Utilizing Postbiotics for the Treatment of Mental Disorders and DGBI
| clinical trial identifier | condition | intervention | status |
|---|---|---|---|
| NCT05475314 (517) | irritable bowel syndrome | microbially fermented postbiotic oat drink | complete |
| NCT05562739 (518) | anxiety | multistrain postbiotic | not yet recruiting |
| NCT05339243 (519) | irritable bowel syndrome with diarrhea | heat-treated Bifidobacterium longum ES1 | recruiting |
Table 9. Highlighted Clinical Trials Utilizing Fecal Microbiota Transplantation for the Treatment of Mental Disorders and DGBI
| clinical trial identifier | condition | intervention | status |
|---|---|---|---|
| NCT03822299 (522) | irritable bowel syndrome | fecal microbiota transplantation | complete |
| NCT02092402 (523) | irritable bowel syndrome | fecal microbiota transplantation | complete |
| NCT05035784 (524) | functional constipation | fecal microbiota transplantation | recruiting |
| NCT05427331 (525) | chronic insomnia | fecal microbiota transplantation capsule | recruiting |
Postbiotic Clinical Trials Landscape for the Treatment of Mental Disorders and DGBI
Clinical study NCT05562739 (recruiting) is researching a multistrain postbiotic for anxiety treatment in individuals who were placebo nonresponders from part one of the trial. A recently completed study (NCT05475314) researched the use of a postbiotic fermented oat drink for the treatment of IBS. The study resulted in positive outcomes and showed symptom relief in IBS subjects. (516) Lastly, clinical trial NCT05339243 is currently recruiting for their study investigating both Bifidobacterium longum ES1 and the postbiotic heat-treated Bifidobacterium longum ES1 for the treatment of IBS symptoms in subjects with diarrhea-predominant IBS.
FMT Clinical Trials Landscape for the Treatment of Mental Disorders and DGBI
Clinical trial NCT05427331 is currently recruiting for its study examining sleep disorders. FMT through oral capsule administration will be researched to access sleep improvement in patients with insomnia. While fecal transplants are less prevalent for mental disorders, they have shown promise for DGBI with clinical trials by showing favorable results for the treatment of IBS. Clinical trial NCT02092402 showed effective treatment for patients with IBS when using a donor with a diverse microbial gut composition. (520) Another study (NCT03822299) also showed success for FMT in IBS. Just as with trial NCT02092402, it also found that the donor’s fecal composition with a favorable microbial signature and diverse gut microbiota was essential for successful treatment. (123) Three years after treatment, the study was still experiencing high response rates and long-standing effects. (521)
Noteworthy Probiotic and Prebiotic Patents
There are a diverse and growing number of patents related to probiotics and prebiotics in the CAS Content Collection. Listed in Table 10 are noteworthy prebiotic and probiotic patents related to the treatment of mental disorders and DGBI.
Table 10. Notable Prebiotic, Probiotic, and Postbiotic Patents
| patent number | title | summary |
|---|---|---|
| WO2016085356A1 | gold kiwifruit compositions and methods of preparation and use thereof | Prebiotic compositions prepared from gold varieties of Actinidia chinensis. These prebiotic compositions treat or prevent DGBI, such as constipation, and IBS. |
| WO2022191767A1 | GOS preconditioning L. reuteri and GOS in final formulation | Enhancing the survival and activity of probiotic Lactobacillus reuteri strains by preconditioning L. reuteri with GOS. This method produces high synbiotic and beneficial effects of the probiotic bacteria in the gastrointestinal tract, such as boosting calcium and iron solubility, along with enhancing the production of lactic and acetic acid. |
| US20160058808A1 | microbe-based modulation of serotonin biosynthesis | Methods and probiotic compositions that can be used to modulate serotonin levels and adjust the composition of gut microbiota along with adjusting the level of serotonin-related metabolites. |
| WO2022182908A1 | probiotic therapies for social deficit and stress response | Bacterial species, including probiotic Enterococcus faecalis, for use in the treatment of social behavioral deficit symptoms, such as depression, by increasing social behavior and decreasing corticosterone levels along with c-Fos expression in the brain. |
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Conclusions and Perspective
ARTICLE SECTIONS
Gut microbiota in humans evolving throughout life has been demonstrated to play a key role in health and disease. In healthy individuals, the intestinal microbiota has a multitude of beneficial functions, including metabolic energy utilization, protection from pathogenic attack, and immunomodulation. Furthermore, it is becoming increasingly documented that bidirectional signaling takes place between the gut and the brain and involves gut microbiota. This relationship encompasses various pathways, such as the vagus nerve; the hypothalamic–pituitary–adrenal axis; and immune, hormonal, and metabolic pathways to control various aspects of homeostasis, including the appropriate development and maintenance of digestive and mental functions. A dysbiosis of the intestinal microbiota is becoming documented as a factor in the pathogenesis of various pathological conditions, including a plethora of mental, metabolic, and digestive disorders. The diverse etiology of these disorders has been related to different microbes, although insufficient information is currently available on the causal direction of the association. Recent impressive advances in next generation sequencing technologies, along with the progress and innovations of metagenomics, metabolomics, multiomics, bioinformatics, and artificial intelligence tools, have provided prospects to better characterize the microbial populations and their functions and help in better correlation prediction. Moreover, studies using germ-free animals have provided important knowledge on causality rather than association. The research focus needs to be further shifted from individual microbes and their role in influencing health and disease toward the gut microbiome ecosystem. A better understanding of fundamental rules driving interactions within gut microbial communities and the dynamics through which they are acquired, transmitted, and adapted to single individuals is needed to make further progress.
The gut microbiome–brain axis embodies a sophisticated network of biological constructs that scientists are only beginning to understand. The nutritional and therapeutic approaches to modulate this axis are ultimately aimed at improving human quality of life. Some products are even already on the market, including foods and supplements that promise to improve gut, mood, sleep, or cognitive performance. The scientific background behind some of these promises is, however, still arguable or unknown.
The gut microbiome offers interesting possibilities to enhance therapies. Future studies should focus on identifying if gut microbiome signatures correlate with fecal/luminal metabolites and/or cytokines that might translate into marked differences in patients’ life. Moreover, more studies evaluating the potential of therapeutic modulation of the microbiome by biotics/fecal transplant to enhance therapeutic options for diseases are needed. Nowadays, research has shown that fecal transplants can restore healthy bacteria in the lower intestine, which can help control diseases caused by pathogenic bacteria. As a result, the first approved fecal transplant drugs are already a fact. Australia’s Therapeutic Goods Administration was the first to grant approval to biotechnology company BiomeBank for its microbiome-based therapy product Biomictra for treating infections from Clostridioides difficile bacteria. (526,527) Days later, the US FDA also approved its first fecal microbiota product Rebyota produced by Ferring Pharmaceuticals for the prevention of recurrence of C. difficile infection in adults. (528)
The multitude of relations between the microbiota, gut, and brain are now well-documented. The next step─moving on from correlative analysis toward understanding the mechanisms behind these relations and identifying the best ways to adapt and adjust the microbiota for potential therapeutic approaches─is now the required pathway. Some of the key setbacks in existing knowledge include understanding the immunological function of specific microbes in the human gut microbiota and their role in neurodegenerative and psychiatric disorders and how microbial metabolites influence brain function in tandem with immunological and neurological signaling molecules.
Despite the advances in microbiome knowledge, a lack of standardization significantly complicates and obstructs comparisons across studies, thus hampering insights into the structure and function of microbial populations. Recent efforts in the introduction of standardized protocols and analytical methods to characterize microbiota and explore the relationships and co-occurrences of microbially related metabolites and microbial taxa (529) would allow for great improvements in examinations of microbial diversity.
One of the significant challenges in microbiota-based medicine is the delineation of healthy microbiota. Variations in microbiota composition between individuals can be large, i.e., microbiota turn out to be pretty much person-specific, which greatly complicates a “one size fits all” strategy in targeting it. However, it also offers chances since the microbiota might be the outlet for an effective future personalized medicine approach. (530) Overall, clinical studies are hampered by the deficiency of specific biomarkers. Yet, recent meta-analyses have validated a positive assessment of the use of psychobiotic interventions for anxiety, schizophrenia, or cognitive performance, which aim at the diversity and complexity of gut microbiota, as well as the various confounding factors that may affect it. (462,531−536)
Although the prevention of brain disorders still remains out of reach, the knowledge of healthy microbiota and their communication pathways could enable an early prediction of such disorders. Thus, the first signs of neurodegenerative conditions, such as Alzheimer’s and Parkinson’s diseases, are known to develop many years before diagnosis. It might become thinkable to slow down neurodegenerative processes by altering the microbiome. Such possibilities have inspired a growing number of scientists to initiate start-up companies examining therapeutics for the treatment of neurological and other disorders through microbiome modulation. Private investors are showing a strong upward trend to fund such clinical research.
Perfecting the gut microbiota through fecal transplants; pro-, pre-, post-, and syn-biotics; healthy diet; and/or healthy lifestyle to control gut micriobiome–brain axis functions and promote mental and digestive health will be a promising field in the future. Patients suffering from mental and/or digestive disorders will get help through such treatments. Healthy individuals will promote their homeostasis and resilience from these remedies.
Supporting Information
ARTICLE SECTIONS
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acschemneuro.3c00127.
Prebiotic, probiotic, postbiotic, and fecal transplant therapeutic clinical trial data investigating the treatment of mental disorders and DGBI through gut microbiome modulation (XLSX)
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.
Author Information
ARTICLE SECTIONS
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Qiongqiong Angela Zhou - CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States;
https://orcid.org/0000-0001-6711-369X;
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Janet M. Sasso - CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States;https://orcid.org/0000-0002-1156-5184
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Rumiana Tenchov - CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States;https://orcid.org/0000-0003-4698-6832
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J.M.S., R.M.A., and R.T. contributed equally to this work.
Acknowledgments
ARTICLE SECTIONS
The authors sincerely appreciate the CAS Data, Analytics & Insights team for their assistance in data extraction. The authors also appreciate Dharmini Patel for project coordination, Manuela Pausan for ideation, and Peter Jap and Cristina Tomeo for insightful discussion. The authors are also grateful to Manuel Guzman, Gilles Georges, Michael Dennis, Dawn Riedel, Dawn George, and Hong Xie for executive sponsorship.
Abbreviations
ARTICLE SECTIONS
| 4-EPS | 4-ethylphenylsulfate |
| 5-AVAB | 5-aminovaleric acid betaine |
| BAs | bile acids |
| BBB | blood-brain barrier |
| BCFA | branched-chain fatty acids |
| CAN | central autonomic network |
| CEN | central executive network |
| CNS | central nervous system |
| DGBI | disorders of gut–brain interaction |
| DMN | default mode network |
| EAN | emotional arousal network |
| ENS | enteric nervous system |
| FC | functional constipation |
| FCT | fecal microbiota transplantation |
| FD | functional dyspepsia |
| FGIDs | functional gastrointestinal disorders |
| GBA | gut–brain axis |
| HC | healthy controls |
| HPA | hypothalamus–pituitary–adrenal |
| IBS | irritable bowel syndrome |
| IHMC | International Human Microbiome Consortium |
| MPs | muramyl peptides |
| OCC | occipital network |
| RDA | recommended daily allowance |
| SAL | salience network |
| SCFA | short-chain fatty acids |
| SMN | sensorimotor network |
| TMAO | trimethylamine-N-oxide |
References
ARTICLE SECTIONS
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17Drews, G. The roots of microbiology and the influence of Ferdinand Cohn on microbiology of the 19th century. FEMS Microbiol. Rev. 2000, 24, 225– 249, DOI: 10.1111/j.1574-6976.2000.tb00540.xGoogle Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXjslOru7g%253D&md5=402d7cf8cd6b2bf3509d72761ad9e6a9The roots of microbiology and the influence of Ferdinand Cohn on microbiology of the 19th centuryDrews, G.FEMS Microbiology Reviews (2000), 24 (3), 225-249CODEN: FMREE4; ISSN:0168-6445. (Elsevier Science B.V.)The beginning of modern microbiol. can be traced back to the 1870s, and it was based on the development of new concepts that originated during the two preceding centuries on the role of microorganisms, new exptl. methods, and discoveries in chem., physics, and evolutionary cell biol. The crucial progress was the isolation and growth on solid media of clone cultures arising from single cells and the demonstration that these pure cultures have specific, inheritable characteristics and metabolic capacities. The doctrine of the spontaneous generation of microorganisms, which stimulated research for a century, lost its role as an important concept. Microorganisms were discovered to be causative agents of infectious diseases and of specific metabolic processes. Microscopy techniques advanced studies on microorganisms. The discovery of sexuality and development in microorganisms and Darwin's theory of evolution contributed to the founding of microbiol. as a science. Ferdinand Cohn (1828-1898), a pioneer in the developmental biol. of lower plants, considerably promoted the taxonomy and physiol. of bacteria, discovered the heat-resistant endospores of bacilli, and was active in applied microbiol.
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18Boundless. Koch’s Postulates. https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/10%3A_Epidemiology/10.1%3A_Principles_of_Epidemiology/10.1D%3A__Kochs_Postulates (accessed October 6, 2022).Google ScholarThere is no corresponding record for this reference.
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22Almeida, A.; Mitchell, A. L.; Boland, M.; Forster, S. C.; Gloor, G. B.; Tarkowska, A.; Lawley, T. D.; Finn, R. D. A new genomic blueprint of the human gut microbiota. Nature 2019, 568, 499– 504, DOI: 10.1038/s41586-019-0965-1Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmslKhu7s%253D&md5=4871997c22d8542f9df02ad2c0066e61A new genomic blueprint of the human gut microbiotaAlmeida, Alexandre; Mitchell, Alex L.; Boland, Miguel; Forster, Samuel C.; Gloor, Gregory B.; Tarkowska, Aleksandra; Lawley, Trevor D.; Finn, Robert D.Nature (London, United Kingdom) (2019), 568 (7753), 499-504CODEN: NATUAS; ISSN:0028-0836. (Nature Research)The compn. of the human gut microbiota is linked to health and disease, but knowledge of individual microbial species is needed to decipher their biol. roles. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. We identify 1952 uncultured candidate bacterial species by reconstructing 92,143 metagenome-assembled genomes from 11,850 human gut microbiomes. These uncultured genomes substantially expand the known species repertoire of the collective human gut microbiota, with a 281% increase in phylogenetic diversity. Although the newly identified species are less prevalent in well-studied populations compared to ref. isolate genomes, they improve classification of understudied African and South American samples by >200%. These candidate species encode hundreds of newly identified biosynthetic gene clusters and possess a distinctive functional capacity that might explain their elusive nature. Our work expands the known diversity of uncultured gut bacteria, which provides unprecedented resoln. for taxonomic and functional characterization of the intestinal microbiota.
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23Hungate, R. E., Chapter IV A Roll Tube Method for Cultivation of Strict Anaerobes. In Methods in Microbiology, Vol. 3; Norris, J. R., Ribbons, D. W., Eds.; Academic Press, 1969; pp 117– 132.Google ScholarThere is no corresponding record for this reference.
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24Cat, L. A. The Decade Of The Microbiome. https://www.forbes.com/sites/linhanhcat/2019/12/31/decade-of-the-microbiome/?sh=7e621a679961 (accessed October 11, 2022).Google ScholarThere is no corresponding record for this reference.
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27Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K. S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464, 59– 65, DOI: 10.1038/nature08821Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXislahsLc%253D&md5=7116690033a12ae47bbe53c77f768e91A human gut microbial gene catalogue established by metagenomic sequencingQin, Junjie; Li, Ruiqiang; Raes, Jeroen; Arumugam, Manimozhiyan; Burgdorf, Kristoffer Solvsten; Manichanh, Chaysavanh; Nielsen, Trine; Pons, Nicolas; Levenez, Florence; Yamada, Takuji; Mende, Daniel R.; Li, Junhua; Xu, Junming; Li, Shaochuan; Li, Dongfang; Cao, Jianjun; Wang, Bo; Liang, Huiqing; Zheng, Huisong; Xie, Yinlong; Tap, Julien; Lepage, Patricia; Bertalan, Marcelo; Batto, Jean-Michel; Hansen, Torben; Le Paslier, Denis; Linneberg, Allan; Nielsen, H. Bjoern; Pelletier, Eric; Renault, Pierre; Sicheritz-Ponten, Thomas; Turner, Keith; Zhu, Hongmei; Yu, Chang; Li, Shengting; Jian, Min; Zhou, Yan; Li, Yingrui; Zhang, Xiuqing; Li, Songgang; Qin, Nan; Yang, Huanming; Wang, Jian; Brunak, Soeren; Dore, Joel; Guarner, Francisco; Kristiansen, Karsten; Pedersen, Oluf; Parkhill, Julian; Weissenbach, Jean; Antolin, Maria; Artiguenave, Francois; Blottiere, Herve; Borruel, Natalia; Bruls, Thomas; Casellas, Francesc; Chervaux, Christian; Cultrone, Antonella; Delorme, Christine; Denariaz, Gerard; Dervyn, Rozenn; Forte, Miguel; Friss, Carsten; van de Guchte, Maarten; Guedon, Eric; Haimet, Florence; Jamet, Alexandre; Juste, Catherine; Kaci, Ghalia; Kleerebezem, Michiel; Knol, Jan; Kristensen, Michel; Layec, Severine; Le Roux, Karine; Leclerc, Marion; Maguin, Emmanuelle; Melo Minardi, Raquel; Oozeer, Raish; Rescigno, Maria; Sanchez, Nicolas; Tims, Sebastian; Torrejon, Toni; Varela, Encarna; de Vos, Willem; Winogradsky, Yohanan; Zoetendal, Erwin; Bork, Peer; Ehrlich, S. Dusko; Wang, JunNature (London, United Kingdom) (2010), 464 (7285), 59-65CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. This report describes the Illumina-based metagenomic sequencing, assembly, and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from fecal samples of 124 European individuals. The gene set, ∼150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbors between 1000 and 1150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. The minimal gut metagenome and the minimal gut bacterial genome are defined and described in terms of functions present in all individuals and most bacteria, resp. Sequence data are deposited in the European Short Read Archive with accession no. ERA000116.
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28Proctor, Lita M. The Human Microbiome Project in 2011 and Beyond. Cell Host Microbe 2011, 10, 287– 291, DOI: 10.1016/j.chom.2011.10.001Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlKisbbL&md5=ca57d3202f3891c261a4b3c7b7d449daThe Human Microbiome Project in 2011 and BeyondProctor, Lita M.Cell Host & Microbe (2011), 10 (4), 287-291CODEN: CHMECB; ISSN:1931-3128. (Cell Press)A review. The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. The authors highlight Human Microbiome Project (HMP) resources, including 600 microbial ref. genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed.
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29Birney, E.; Stamatoyannopoulos, J. A.; Dutta, A.; Guigó, R.; Gingeras, T. R.; Margulies, E. H.; Weng, Z.; Snyder, M.; Dermitzakis, E. T.; Stamatoyannopoulos, J. A. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007, 447, 799– 816, DOI: 10.1038/nature05874Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXms1Wjsb0%253D&md5=727de4c5a83d3f75af54e31f974472a7Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectBirney, Ewan; Stamatoyannopoulos, John A.; Dutta, Anindya; Guigo, Roderic; Gingeras, Thomas R.; Margulies, Elliott H.; Weng, Zhiping; Snyder, Michael; Dermitzakis, Emmanouil T.; Stamatoyannopoulos, John A.; Thurman, Robert E.; Kuehn, Michael S.; Taylor, Christopher M.; Neph, Shane; Koch, Christoph M.; Asthana, Saurabh; Malhotra, Ankit; Adzhubei, Ivan; Greenbaum, Jason A.; Andrews, Robert M.; Flicek, Paul; Boyle, Patrick J.; Cao, Hua; Carter, Nigel P.; Clelland, Gayle K.; Davis, Sean; Day, Nathan; Dhami, Pawandeep; Dillon, Shane C.; Dorschner, Michael O.; Fiegler, Heike; Giresi, Paul G.; Goldy, Jeff; Hawrylycz, Michael; Haydock, Andrew; Humbert, Richard; James, Keith D.; Johnson, Brett E.; Johnson, Ericka M.; Frum, Tristan T.; Rosenzweig, Elizabeth R.; Karnani, Neerja; Lee, Kirsten; Lefebvre, Gregory C.; Navas, Patrick A.; Neri, Fidencio; Parker, Stephen C. J.; Sabo, Peter J.; Sandstrom, Richard; Shafer, Anthony; Vetrie, David; Weaver, Molly; Wilcox, Sarah; Yu, Man; Collins, Francis S.; Dekker, Job; Lieb, Jason D.; Tullius, Thomas D.; Crawford, Gregory E.; Sunyaev, Shamil; Noble, William S.; Dunham, Ian; Dutta, Anindya; Guigo, Roderic; Denoeud, France; Reymond, Alexandre; Kapranov, Philipp; Rozowsky, Joel; Zheng, Deyou; Castelo, Robert; Frankish, Adam; Harrow, Jennifer; Ghosh, Srinka; Sandelin, Albin; Hofacker, Ivo L.; Baertsch, Robert; Keefe, Damian; Flicek, Paul; Dike, Sujit; Cheng, Jill; Hirsch, Heather A.; Sekinger, Edward A.; Lagarde, Julien; Abril, Josep F.; Shahab, Atif; Flamm, Christoph; Fried, Claudia; Hackermueller, Joerg; Hertel, Jana; Lindemeyer, Manja; Missal, Kristin; Tanzer, Andrea; Washietl, Stefan; Korbel, Jan; Emanuelsson, Olof; Pedersen, Jakob S.; Holroyd, Nancy; Taylor, Ruth; Swarbreck, David; Matthews, Nicholas; Dickson, Mark C.; Thomas, Daryl J.; Weirauch, Matthew T.; Gilbert, James; Drenkow, Jorg; Bell, Ian; Zhao, Xiao Dong; Srinivasan, K. G.; Sung, Wing-Kin; Ooi, Hong Sain; Chiu, Kuo Ping; Foissac, Sylvain; Alioto, Tyler; Brent, Michael; Pachter, Lior; Tress, Michael L.; Valencia, Alfonso; Choo, Siew Woh; Choo, Chiou Yu; Ucla, Catherine; Manzano, Caroline; Wyss, Carine; Cheung, Evelyn; Clark, Taane G.; Brown, James B.; Ganesh, Madhavan; Patel, Sandeep; Tammana, Hari; Chrast, Jacqueline; Henrichsen, Charlotte N.; Kai, Chikatoshi; Kawai, Jun; Nagalakshmi, Ugrappa; Wu, Jiaqian; Lian, Zheng; Lian, Jin; Newburger, Peter; Zhang, Xueqing; Bickel, Peter; Mattick, John S.; Carninci, Piero; Hayashizaki, Yoshihide; Weissman, Sherman; Dermitzakis, Emmanouil T.; Margulies, Elliott H.; Hubbard, Tim; Myers, Richard M.; Rogers, Jane; Stadler, Peter F.; Lowe, Todd M.; Wei, Chia-Lin; Ruan, Yijun; Snyder, Michael; Birney, Ewan; Struhl, Kevin; Gerstein, Mark; Antonarakis, Stylianos E.; Gingeras, Thomas R.; Brown, James B.; Flicek, Paul; Fu, Yutao; Keefe, Damian; Birney, Ewan; Denoeud, France; Gerstein, Mark; Green, Eric D.; Kapranov, Philipp; Karaoez, Ulas; Myers, Richard M.; Noble, William S.; Reymond, Alexandre; Rozowsky, Joel; Struhl, Kevin; Siepel, Adam; Stamatoyannopoulos, John A.; Taylor, Christopher M.; Taylor, James; Thurman, Robert E.; Tullius, Thomas D.; Washietl, Stefan; Zheng, Deyou; Liefer, Laura A.; Wetterstrand, Kris A.; Good, Peter J.; Feingold, Elise A.; Guyer, Mark S.; Collins, Francis S.; Margulies, Elliott H.; Cooper, Gregory M.; Asimenos, George; Thomas, Daryl J.; Dewey, Colin N.; Siepel, Adam; Birney, Ewan; Keefe, Damian; Hou, Minmei; Taylor, James; Nikolaev, Sergey; Montoya-Burgos, Juan I.; Loeytynoja, Ari; Whelan, Simon; Pardi, Fabio; Massingham, Tim; Brown, James B.; Huang, Haiyan; Zhang, Nancy R.; Bickel, Peter; Holmes, Ian; Mullikin, James C.; Ureta-Vidal, Abel; Paten, Benedict; Seringhaus, Michael; Church, Deanna; Rosenbloom, Kate; Kent, W. James; Stone, Eric A.; Gerstein, Mark; Antonarakis, Stylianos E.; Batzoglou, Serafim; Goldman, Nick; Hardison, Ross C.; Haussler, David; Miller, Webb; Pachter, Lior; Green, Eric D.; Sidow, Arend; Weng, Zhiping; Trinklein, Nathan D.; Fu, Yutao; Zhang, Zhengdong D.; Karaoez, Ulas; Barrera, Leah; Stuart, Rhona; Zheng, Deyou; Ghosh, Srinka; Flicek, Paul; King, David C.; Taylor, James; Ameur, Adam; Enroth, Stefan; Bieda, Mark C.; Koch, Christoph M.; Hirsch, Heather A.; Wei, Chia-Lin; Cheng, Jill; Kim, Jonghwan; Bhinge, Akshay A.; Giresi, Paul G.; Jiang, Nan; Liu, Jun; Yao, Fei; Sung, Wing-Kin; Chiu, Kuo Ping; Vega, Vinsensius B.; Lee, Charlie W. H.; Ng, Patrick; Shahab, Atif; Sekinger, Edward A.; Yang, Annie; Moqtaderi, Zarmik; Zhu, Zhou; Xu, Xiaoqin; Squazzo, Sharon; Oberley, Matthew J.; Inman, David; Singer, Michael A.; Richmond, Todd A.; Munn, Kyle J.; Rada-Iglesias, Alvaro; Wallerman, Ola; Komorowski, Jan; Clelland, Gayle K.; Wilcox, Sarah; Dillon, Shane C.; Andrews, Robert M.; Fowler, Joanna C.; Couttet, Phillippe; James, Keith D.; Lefebvre, Gregory C.; Bruce, Alexander W.; Dovey, Oliver M.; Ellis, Peter D.; Dhami, Pawandeep; Langford, Cordelia F.; Carter, Nigel P.; Vetrie, David; Kapranov, Philipp; Nix, David A.; Bell, Ian; Patel, Sandeep; Rozowsky, Joel; et al.Nature (London, United Kingdom) (2007), 447 (7146), 799-816CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)We report the generation and anal. of functional data from multiple, diverse expts. performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a no. of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examn. of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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30Riesenfeld, C. S.; Schloss, P. D.; Handelsman, J. Metagenomics: Genomic Analysis of Microbial Communities. Annu. Rev. Genet. 2004, 38, 525– 552, DOI: 10.1146/annurev.genet.38.072902.091216Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXltlyjtg%253D%253D&md5=84d6562bb905baacfe91982a2151722dMetagenomics: Genomic analysis of microbial communitiesRiesenfeld, Christian S.; Schloss, Patrick D.; Handelsman, JoAnnual Review of Genetics (2004), 38 (), 525-552CODEN: ARVGB7; ISSN:0066-4197. (Annual Reviews Inc.)A review. Uncultured microorganisms comprise the majority of the planet's biol. diversity. Microorganisms represent two of the three domains of life and contain vast diversity that is the product of an estd. 3.8 billion years of evolution. In many environments, as many as 99% of the microorganisms cannot be cultured by std. techniques, and the uncultured fraction includes diverse organisms that are only distantly related to the cultured ones. Therefore, culture-independent methods are essential to understand the genetic diversity, population structure, and ecol. roles of the majority of microorganisms. Metagenomics, or the culture-independent genomic anal. of an assemblage of microorganisms, has potential to answer fundamental questions in microbial ecol. This review describes progress toward understanding the biol. of uncultured Bacteria, Archaea, and viruses through metagenomic analyses.
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31Jandhyala, S. M.; Talukdar, R.; Subramanyam, C.; Vuyyuru, H.; Sasikala, M.; Nageshwar Reddy, D. Role of the normal gut microbiota. World J. Gastroenterol. 2015, 21, 8787– 8803, DOI: 10.3748/wjg.v21.i29.8787Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XosVSlsw%253D%253D&md5=b0cd06c0ec390547e6248afb8e782139Role of the normal gut microbiotaJandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Reddy, D. NageshwarWorld Journal of Gastroenterology (2015), 21 (29), 8787-8803CODEN: WJGAF2; ISSN:2219-2840. (Baishideng Publishing Group Inc.)Relation between the gut microbiota and human health is being increasingly recognized. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metab., xenobiotic and drug metab., maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like mols. that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.
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32Tomas, J.; Wrzosek, L.; Bouznad, N.; Bouet, S.; Mayeur, C.; Noordine, M. L.; Honvo-Houeto, E.; Langella, P.; Thomas, M.; Cherbuy, C. Primocolonization is associated with colonic epithelial maturation during conventionalization. FASEB J. 2013, 27, 645– 655, DOI: 10.1096/fj.12-216861Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXit1Skur0%253D&md5=311f2c67cbf2a56fdc02893385a4190bPrimocolonization is associated with colonic epithelial maturation during conventionalizationTomas, Julie; Wrzosek, Laura; Bouznad, Nassim; Bouet, Stephan; Mayeur, Camille; Noordine, Marie-Louise; Honvo-Houeto, Edith; Langella, Philippe; Thomas, Muriel; Cherbuy, ClaireFASEB Journal (2013), 27 (2), 645-655, 10.1096/fj.12-216861CODEN: FAJOEC; ISSN:0892-6638. (Federation of American Societies for Experimental Biology)Interaction between the gut microbiota and the host starts immediately after birth with the progressive colonization of the sterile intestine. Our aim was to investigate the interactions taking place in the colonic epithelium after the first exposure to gut microbiota. Germ-free (GF) rats were inoculated with two different microbiotas: the first, obtained from suckling rats, was rich in primocolonizing bacteria and the second, obtained from adult rats, was representative of a mature microbiota. Once transferred into GF rats, these two microbiotas evolved such that they converged, and recapitulated the primocolonization pattern, mimicking the chronol. scheme of implantation following birth. The two microbiotas induced common responses in the colonic epithelium: a transitory proliferative phase followed by a compensatory phase characterized by increases in the abundance of p21Cip1 and p27Kip1 and in the no. of goblet cells. The effects of the two microbiotas diverged only through their effects on colonic transporters. Analyses of solute carriers and aquaporins revealed that functional maturation was more pronounced following exposure to adult microbiota than suckling microbiota. The colon matured in parallel with the evolution of the microbiota compn., and we therefore suggest a link between intestinal events regulating homeostasis of the colon and modulation of microbial compn.
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33Caballero, S.; Pamer, E. G. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu. Rev. Immunol. 2015, 33, 227– 256, DOI: 10.1146/annurev-immunol-032713-120238Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVSisL3M&md5=9f613a189ee2cb8447e3e7330eb4bc4dMicrobiota-Mediated Inflammation and Antimicrobial Defense in the IntestineCaballero, Silvia; Pamer, Eric G.Annual Review of Immunology (2015), 33 (), 227-256CODEN: ARIMDU; ISSN:0732-0582. (Annual Reviews)The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools, and full-genome characterization of several hundred commensal bacterial species facilitated studies of the microbiota and revealed that differences in microbiota compn. can be assocd. with inflammatory, metabolic, and infectious diseases, that each human is colonized by a distinct bacterial flora, and that the microbiota can be manipulated to reduce and even cure some diseases. Different bacterial species induce distinct immune cell populations that can play pro- and anti-inflammatory roles, and thus the compn. of the microbiota dets., in part, the level of resistance to infection and susceptibility to inflammatory diseases. This review summarizes recent work characterizing commensal microbes that contribute to the antimicrobial defense/inflammation axis.
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34Magnúsdóttir, S.; Ravcheev, D.; de Crécy-Lagard, V.; Thiele, I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Frontiers in Genetics 2015, 6, 148, DOI: 10.3389/fgene.2015.00148Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MfgvVWltA%253D%253D&md5=4f500bfea9a3f72d0e88539d7e3ccfcfSystematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbesMagnusdottir Stefania; Ravcheev Dmitry; Thiele Ines; de Crecy-Lagard ValerieFrontiers in genetics (2015), 6 (), 148 ISSN:1664-8021.The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40-65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements.
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35Mayer, E. A.; Knight, R.; Mazmanian, S. K.; Cryan, J. F.; Tillisch, K. Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 2014, 34, 15490– 15496, DOI: 10.1523/JNEUROSCI.3299-14.2014Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2M3nvVKktw%253D%253D&md5=94069bb4e4d54c2afed184e28851a2c6Gut microbes and the brain: paradigm shift in neuroscienceMayer Emeran A; Knight Rob; Mazmanian Sarkis K; Cryan John F; Tillisch KirstenThe Journal of neuroscience : the official journal of the Society for Neuroscience (2014), 34 (46), 15490-6 ISSN:.The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject.
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36Clarke, G.; Grenham, S.; Scully, P.; Fitzgerald, P.; Moloney, R. D.; Shanahan, F.; Dinan, T. G.; Cryan, J. F. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 2013, 18, 666– 673, DOI: 10.1038/mp.2012.77Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1aku7w%253D&md5=46c3ff1746ad758d4af322c058f8b4cbThe microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent mannerClarke, G.; Grenham, S.; Scully, P.; Fitzgerald, P.; Moloney, R. D.; Shanahan, F.; Dinan, T. G.; Cryan, J. F.Molecular Psychiatry (2013), 18 (6), 666-673CODEN: MOPSFQ; ISSN:1359-4184. (Nature Publishing Group)Bacterial colonization of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclin. tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concn. of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonized control animals. Moreover, this alteration is sex specific in contrast with the immunol. and neuroendocrine effects which are evident in both sexes. Concns. of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonization of the GF animals post weaning is insufficient to reverse the CNS neurochem. consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addn., reduced anxiety in GF animals is also normalized following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochem., but not behavioral, profile is resistant to restoration of a normal gut flora in later life. Mol. Psychiatry (2013) 18, 666-673; doi:10.1038/mp.2012.77; published online 12 June 2012.
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37Bray, N. The microbiota–gut–brain axis. https://www.nature.com/articles/d42859-019-00021-3 (accessed October 6, 2022).Google ScholarThere is no corresponding record for this reference.
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38Dinan, T. G.; Cryan, J. F. The impact of gut microbiota on brain and behaviour: implications for psychiatry. Curr. Opin. Clin. Nutr. Metab. Care 2015, 18, 552– 558, DOI: 10.1097/MCO.0000000000000221Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC283itlCitw%253D%253D&md5=66e25889e8960eb947e2384e8782ebb3The impact of gut microbiota on brain and behaviour: implications for psychiatryDinan Timothy G; Cryan John FCurrent opinion in clinical nutrition and metabolic care (2015), 18 (6), 552-8 ISSN:.PURPOSE OF REVIEW: The gut microbiota has become a focus of research for those interested in the brain and behaviour. Here, we profile the gut microbiota in a variety of neuropsychiatric syndromes. RECENT FINDINGS: Multiple routes of communication between the gut and brain have been established and these include the vagus nerve, immune system, short chain fatty acids and tryptophan. Developmentally, those born by caesarean section have a distinctly different microbiota in early life to those born per vaginum. At the other extreme, individuals who age with considerable ill-heath tend to show narrowing in microbial diversity. Recently, the gut microbiota has been profiled in a variety of conditions including autism, major depression and Parkinson's disease. There is still debate as to whether or not these changes are core to the pathophysiology or merely epiphenomenal. SUMMARY: The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.
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39Bravo, J. A.; Forsythe, P.; Chew, M. V.; Escaravage, E.; Savignac, H. M.; Dinan, T. G.; Bienenstock, J.; Cryan, J. F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 16050– 16055, DOI: 10.1073/pnas.1102999108Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1ekt7nF&md5=f87375fac8abc7761ef696afb9b42a59Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerveBravo, Javier A.; Forsythe, Paul; Chew, Marianne V.; Escaravage, Emily; Savignac, Helene M.; Dinan, Timothy G.; Bienenstock, John; Cryan, Ohn F.Proceedings of the National Academy of Sciences of the United States of America (2011), 108 (38), 16050-16055, S16050/1-S16050/7CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiol. and psychol. processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant redns. in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addn., L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone. and anxiety- and depression-related behavior. Moreover, the neurochem. and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress- related disorders such as anxiety and depression.
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40Cohen-Sacks, H.; Elazar, V.; Gao, J.; Golomb, A.; Adwan, H.; Korchov, N.; Levy, R. J.; Berger, M. R.; Golomb, G. Delivery and expression of pDNA embedded in collagen matrices. J. Controlled Release 2004, 95, 309– 320, DOI: 10.1016/j.jconrel.2003.11.001Google Scholar40https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhsVCms7w%253D&md5=7cee5279df6c140cab54b64d33b4bb13Delivery and expression of pDNA embedded in collagen matricesCohen-Sacks, Hagit; Elazar, Victoria; Gao, Jianchuan; Golomb, Assaf; Adwan, Hassan; Korchov, Nikoly; Levy, Robert J.; Berger, Martin R.; Golomb, GershonJournal of Controlled Release (2004), 95 (2), 309-320CODEN: JCREEC; ISSN:0168-3659. (Elsevier)Collagen matrixes can be used as non-viral biocompatible gene carriers for localized implantable gene therapy. Collagen matrixes embedding pDNA with enhanced binding through condensing agent linkage to the matrix or to the pDNA have been formulated, and characterized in various systems. PDNA and condensed pDNA were released intact from the matrixes within 1-2 days. In vitro transfection with collagen matrixes contg. pDNA (luciferase encoding), pDNA in liposome (LIP), and pDNA with polyethylenimine (PEI) resulted in significantly higher expression levels in comparison to naked pDNA. PDNA-LIP matrixes exhibited a dose response transfection of NIH 3T3, 293, MDA-MB-231 and smooth muscle cells (SMCs) in cell cultures. Subdermal implantations of collagen-polylysine-pDNA matrixes in rats resulted in significantly higher gene expression levels in comparison to non-condensed pDNA matrixes. Perivascular treatment with pDNA matrix and of naked pDNA soln. in balloon-injured rat carotid arteries resulted in significant expression. In conclusion, a facile method for embedding cationic formulations of pDNA in collagen matrixes was developed. These bioactive matrixes seem to be suitable for tissue engineering and local gene therapy strategies.
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41Rutsch, A.; Kantsjö, J. B.; Ronchi, F. The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. Front. Immunol. 2020, 11, 604179, DOI: 10.3389/fimmu.2020.604179Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitVCnsL8%253D&md5=ae2dc7a2f0e92a3158a44011755e4cdcThe gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathologyRutsch, Andrina; Kantsjo, Johan B.; Ronchi, FrancescaFrontiers in Immunology (2020), 11 (), 604179CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. The human microbiota has a fundamental role in host physiol. and pathol. Gut microbial alteration, also known as dysbiosis, is a condition assocd. not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiol. and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gutbrain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and assocd. with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressivelike disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the prodn. of proinflammatory cytokines (interleukin-1b and interleukin-1β) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.
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42Drossman, D. A.; Hasler, W. L. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology 2016, 150, 1257– 1261, DOI: 10.1053/j.gastro.2016.03.035Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28bmsFyhsQ%253D%253D&md5=27727046d3fb8623210eb13dcae74c85Rome IV-Functional GI Disorders: Disorders of Gut-Brain InteractionDrossman Douglas A; Hasler William LGastroenterology (2016), 150 (6), 1257-61 ISSN:.There is no expanded citation for this reference.
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43Perez-Muñoz, M. E.; Arrieta, M.-C.; Ramer-Tait, A. E.; Walter, J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 2017, 5, 48, DOI: 10.1186/s40168-017-0268-4Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1critlWquw%253D%253D&md5=ed193fdc5a2e0d6896d48b5d74a43cd7A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiomePerez-Munoz Maria Elisa; Walter Jens; Arrieta Marie-Claire; Arrieta Marie-Claire; Ramer-Tait Amanda E; Walter JensMicrobiome (2017), 5 (1), 48 ISSN:.After more than a century of active research, the notion that the human fetal environment is sterile and that the neonate's microbiome is acquired during and after birth was an accepted dogma. However, recent studies using molecular techniques suggest bacterial communities in the placenta, amniotic fluid, and meconium from healthy pregnancies. These findings have led many scientists to challenge the "sterile womb paradigm" and propose that microbiome acquisition instead begins in utero, an idea that would fundamentally change our understanding of gut microbiota acquisition and its role in human development. In this review, we provide a critical assessment of the evidence supporting these two opposing hypotheses, specifically as it relates to (i) anatomical, immunological, and physiological characteristics of the placenta and fetus; (ii) the research methods currently used to study microbial populations in the intrauterine environment; (iii) the fecal microbiome during the first days of life; and (iv) the generation of axenic animals and humans. Based on this analysis, we argue that the evidence in support of the "in utero colonization hypothesis" is extremely weak as it is founded almost entirely on studies that (i) used molecular approaches with an insufficient detection limit to study "low-biomass" microbial populations, (ii) lacked appropriate controls for contamination, and (iii) failed to provide evidence of bacterial viability. Most importantly, the ability to reliably derive axenic animals via cesarean sections strongly supports sterility of the fetal environment in mammals. We conclude that current scientific evidence does not support the existence of microbiomes within the healthy fetal milieu, which has implications for the development of clinical practices that prevent microbiome perturbations after birth and the establishment of future research priorities.
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44Dominguez-Bello, M. G.; Costello, E. K.; Contreras, M.; Magris, M.; Hidalgo, G.; Fierer, N.; Knight, R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 11971– 11975, DOI: 10.1073/pnas.1002601107Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cnlslKksg%253D%253D&md5=0aaa3ce83c3d727862accea6cbc2401aDelivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newbornsDominguez-Bello Maria G; Costello Elizabeth K; Contreras Monica; Magris Magda; Hidalgo Glida; Fierer Noah; Knight RobProceedings of the National Academy of Sciences of the United States of America (2010), 107 (26), 11971-5 ISSN:.Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.
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45Hill, C. J.; Lynch, D. B.; Murphy, K.; Ulaszewska, M.; Jeffery, I. B.; O’Shea, C. A.; Watkins, C.; Dempsey, E.; Mattivi, F.; Tuohy, K. Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome 2017, 5, 4, DOI: 10.1186/s40168-016-0213-yGoogle Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1c7msFykug%253D%253D&md5=37ab7baa46268117464df0482f93e01aEvolution of gut microbiota composition from birth to 24 weeks in the INFANTMET CohortHill Cian J; Lynch Denise B; Murphy Kiera; Jeffery Ian B; Ross R Paul; O' Toole Paul W; Hill Cian J; Lynch Denise B; Murphy Kiera; Ross R Paul; Ryan C Anthony; O' Toole Paul W; Stanton Catherine; Murphy Kiera; Watkins Claire; Stanton Catherine; Ulaszewska Marynka; Mattivi Fulvio; Tuohy Kieran; O'Shea Carol Anne; Dempsey Eugene; Ryan C AnthonyMicrobiome (2017), 5 (1), 4 ISSN:.BACKGROUND: The gut is the most extensively studied niche of the human microbiome. The aim of this study was to characterise the initial gut microbiota development of a cohort of breastfed infants (n = 192) from 1 to 24 weeks of age. METHODS: V4-V5 region 16S rRNA amplicon Illumina sequencing and, in parallel, bacteriological culture. The metabolomic profile of infant urine at 4 weeks of age was also examined by LC-MS. RESULTS: Full-term (FT), spontaneous vaginally delivered (SVD) infants' microbiota remained stable at both phylum and genus levels during the 24-week period examined. FT Caesarean section (CS) infants displayed an increased faecal abundance of Firmicutes (p < 0.01) and lower abundance of Actinobacteria (p < 0.001) after the first week of life compared to FT-SVD infants. FT-CS infants gradually progressed to harbouring a microbiota closely resembling FT-SVD (which remained stable) by week 8 of life, which was maintained at week 24. The gut microbiota of preterm (PT) infants displayed a significantly greater abundance of Proteobacteria compared to FT infants (p < 0.001) at week 1. Metabolomic analysis of urine at week 4 indicated PT-CS infants have a functionally different metabolite profile than FT (both CS and SVD) infants. Co-inertia analysis showed co-variation between the urine metabolome and the faecal microbiota of the infants. Tryptophan and tyrosine metabolic pathways, as well as fatty acid and bile acid metabolism, were found to be affected by delivery mode and gestational age. CONCLUSIONS: These findings confirm that mode of delivery and gestational age both have significant effects on early neonatal microbiota composition. There is also a significant difference between the metabolite profile of FT and PT infants. Prolonged breastfeeding was shown to have a significant effect on the microbiota composition of FT-CS infants at 24 weeks of age, but interestingly not on that of FT-SVD infants. Twins had more similar microbiota to one another than between two random infants, reflecting the influence of similarities in both host genetics and the environment on the microbiota..
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46Vatanen, T.; Jabbar, K. S.; Ruohtula, T.; Honkanen, J.; Avila-Pacheco, J.; Siljander, H.; Stražar, M.; Oikarinen, S.; Hyöty, H.; Ilonen, J. Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism. Cell 2022, 185, 4921– 4936.e4915, DOI: 10.1016/j.cell.2022.11.023Google Scholar46https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtFOktr7P&md5=1185b098b457b0ef3cfe3ea2f2d498c0Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolismVatanen, Tommi; Jabbar, Karolina S.; Ruohtula, Terhi; Honkanen, Jarno; Avila-Pacheco, Julian; Siljander, Heli; Strazar, Martin; Oikarinen, Sami; Hyoty, Heikki; Ilonen, Jorma; Mitchell, Caroline M.; Yassour, Moran; Virtanen, Suvi M.; Clish, Clary B.; Plichta, Damian R.; Vlamakis, Hera; Knip, Mikael; Xavier, Ramnik J.Cell (Cambridge, MA, United States) (2022), 185 (26), 4921-4936.e15CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The perinatal period represents a crit. window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 yr of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes assocd. with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite assocns. not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular-but not extensively hydrolyzed-formula were distinct from those of exclusively breastfed infants. Taken together, our integrative anal. expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life.
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47Baleato, C. L.; Ferguson, J. J. A.; Oldmeadow, C.; Mishra, G. D.; Garg, M. L. Plant-Based Dietary Patterns versus Meat Consumption and Prevalence of Impaired Glucose Intolerance and Diabetes Mellitus: A Cross-Sectional Study in Australian Women. Nutrients 2022, 14, 4152, DOI: 10.3390/nu14194152Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xis1yltr%252FJ&md5=3ba139d4a14dc5178154790ac8c366b9Plant-Based Dietary Patterns versus Meat Consumption and Prevalence of Impaired Glucose Intolerance and Diabetes Mellitus: A Cross-Sectional Study in Australian WomenBaleato, Courtney L.; Ferguson, Jessica J. A.; Oldmeadow, Christopher; Mishra, Gita D.; Garg, Manohar L.Nutrients (2022), 14 (19), 4152CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)This study aimed to compare the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) among Australian women following plant-based diets (PBD) compared to regular meat eaters. A cross sectional anal. of the mid-aged cohort (1946-1951) of the Australian Longitudinal Study on Women's Health was conducted on completers of Survey 7 in 2013 with complete FFQ data available (n = 9102). Dietary patterns were categorized as PBD (vegan, lacto-ovo vegetarian, pesco-vegetarian, semi-vegetarian) and regular meat eaters. Meat eaters were further categorized into high and low consumption and outcomes included self-reported prevalence of IGT and DM. Participants were identified as regular meat eaters (n = 8937) and PBD (n = 175). Prevalence of IGT was lower in PBD (0-1.2%) compared to regular meat eaters (9.1%). Consolidation of PBD to a single group (vegetarians) indicated a lower prevalence of DM in vegetarians compared to regular meat eaters (3.9% vs. 9.1%). Women consuming meat daily/multiple times per day had significantly higher odds of IGT (OR 1.5, 95%CI 1.1 to 2.1, p = 0.02). Individuals consuming processed meat daily/multiple times per day had significantly higher odds of DM compared to those consuming less than daily (Odds ratio (OR) 1.7, 95% confidence interval (CI) 1.3 to 2.3, p < 0.0001). After adjustment for covariates, statistical significance was lost largely due to the addn. of BMI to the model. Prevalence of IGT and DM were lower in women following PBD and higher in high consumers of meat and processed meat. The relationship between meat consumption and IGT/diabetes status appears to be mediated, at least in part, by an increase in body mass index (BMI). Future studies are warranted to investigate the mechanisms and other lifestyle factors underpinning the assocn. between high meat consumption and increased risk of IGT and DM.
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48Keaver, L.; Ruan, M.; Chen, F.; Du, M.; Ding, C.; Wang, J.; Shan, Z.; Liu, J.; Zhang, F. F. Plant- and animal-based diet quality and mortality among US adults: a cohort study. Br. J. Nutr. 2021, 125, 1405– 1415, DOI: 10.1017/S0007114520003670Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtFaisLbF&md5=8f55f34569e6b7dd7575a1a841dffd7dPlant- and animal-based diet quality and mortality among US adults: a cohort studyKeaver, Laura; Ruan, Mengyuan; Chen, Fan; Du, Mengxi; Ding, Chenyueyi; Wang, Jiaqi; Shan, Zhilei; Liu, Junxiu; Zhang, Fang FangBritish Journal of Nutrition (2021), 125 (12), 1405-1415CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)Not all plant-based and animal foods exert the same health effects due to their various nutrient compns. We aimed to assess the quality of plant-based v. animal foods in relation to mortality in a prospective cohort study. Using data collected from a nationally representative sample of 36 825 adults in the National Health and Nutrition Examn. Survey 1999-2014, we developed a de novo Comprehensive Diet Quality Index (cDQI) that assesses the quality of seventeen foods based on the healthfulness and sep. scored the quality of eleven plant-based foods in a plant-based Diet Quality Index (pDQI) and six animal foods in an animal-based Diet Quality Index (aDQI). Mortality from all causes, heart disease and cancer were obtained from linkage to the National Death Index up to 31 Dec. 2015. Cox proportional hazard models were used to est. hazard ratios (HR) and 95 % CI after multivariable adjustments. During a median follow-up of 8·3 years, 4669 all-cause deaths occurred, including 798 deaths due to heart disease and 1021 due to cancer. Compared with individuals in the lowest quartile, those in the highest quartile of cDQI had a lower risk of all-cause mortality (HR 0·75, 95 % CI 0·65, 0·86; P trend < 0·001), which largely reflected the inverse relationship between quality of plant-based foods (pDQI) and all-cause mortality (HR 0·66, 95 % CI 0·58, 0·74; P trend < 0·001). No independent assocn. was found for the quality of animal foods (aDQI) and mortality. Our results suggest that consuming healthy plant-based foods is assocd. with lower all-cause mortality among US adults.
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49O’Mahony, S. M.; Marchesi, J. R.; Scully, P.; Codling, C.; Ceolho, A.-M.; Quigley, E. M. M.; Cryan, J. F.; Dinan, T. G. Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses. Biol. Psychiatry 2009, 65, 263– 267, DOI: 10.1016/j.biopsych.2008.06.026Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M%252FntlSrug%253D%253D&md5=5fc242a46520953c886d1a25e854f9a0Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnessesO'Mahony Siobhain M; Marchesi Julian R; Scully Paul; Codling Caroline; Ceolho Anne-Marie; Quigley Eamonn M M; Cryan John F; Dinan Timothy GBiological psychiatry (2009), 65 (3), 263-7 ISSN:.BACKGROUND: Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable. METHODS: The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2-12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed. RESULTS: The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group. CONCLUSIONS: These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.
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50Jernberg, C.; Löfmark, S.; Edlund, C.; Jansson, J. K. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology (Reading) 2010, 156, 3216– 3223, DOI: 10.1099/mic.0.040618-0Google Scholar50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFCiur3F&md5=56649fa26b86128690cb19944423b1adLong-term impacts of antibiotic exposure on the human intestinal microbiotaJernberg, Cecilia; Loefmark, Sonja; Edlund, Charlotta; Jansson, Janet K.Microbiology (Reading, United Kingdom) (2010), 156 (11), 3216-3223CODEN: MROBEO; ISSN:1350-0872. (Society for General Microbiology)A review. Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that the impacts of some antibiotics remain for extended periods of time. In addn., antibiotic-resistant strains can persist in the human host environment in the absence of selective pressure. Both mol.- and cultivation-based approaches have revealed ecol. disturbances in the microbiota after antibiotic administration, in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question. A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic-resistant pathogenic strains.
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51Caporaso, J. G.; Kuczynski, J.; Stombaugh, J.; Bittinger, K.; Bushman, F. D.; Costello, E. K.; Fierer, N.; Peña, A. G.; Goodrich, J. K.; Gordon, J. I. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 2010, 7, 335– 336, DOI: 10.1038/nmeth.f.303Google Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXksFalurg%253D&md5=0f3e337921b1cc48bc697f0ee92bf5b8QIIME allows analysis of high-throughput community sequencing dataCaporaso, J. Gregory; Kuczynski, Justin; Stombaugh, Jesse; Bittinger, Kyle; Bushman, Frederic D.; Costello, Elizabeth K.; Fierer, Noah; Pena, Antonio Gonzalez; Goodrich, Julia K.; Gordon, Jeffrey I.; Huttley, Gavin A.; Kelley, Scott T.; Knights, Dan; Koenig, Jeremy E.; Ley, Ruth E.; Lozupone, Catherine A.; McDonald, Daniel; Muegge, Brian D.; Pirrung, Meg; Reeder, Jens; Sevinsky, Joel R.; Turnbaugh, Peter J.; Walters, William A.; Widmann, Jeremy; Yatsunenko, Tanya; Zaneveld, Jesse; Knight, RobNature Methods (2010), 7 (5), 335-336CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)There is no expanded citation for this reference.
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52Tang, L. Sequence-based identification of human-associated microbiota. https://www.nature.com/articles/d42859-019-00011-5 (accessed October 24, 2022).Google ScholarThere is no corresponding record for this reference.
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53Collins, S. M.; Surette, M.; Bercik, P. The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 2012, 10, 735– 742, DOI: 10.1038/nrmicro2876Google Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhtlylt7%252FJ&md5=097611d85e63be4c96cb92f83be0367dThe interplay between the intestinal microbiota and the brainCollins, Stephen M.; Surette, Michael; Bercik, PremyslNature Reviews Microbiology (2012), 10 (11), 735-742CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)A review. The intestinal microbiota consists of a vast bacterial community that resides primarily in the lower gut and lives in a symbiotic relationship with the host. A bidirectional neurohumoral communication system, known as the gut-brain axis, integrates the host gut and brain activities. Here, we describe the recent advances in our understanding of how the intestinal microbiota communicates with the brain via this axis to influence brain development and behavior. We also review how this extended communication system might influence a broad spectrum of diseases, including irritable bowel syndrome, psychiatric disorders and demyelinating conditions such as multiple sclerosis.
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54Lagier, J.-C.; Armougom, F.; Million, M.; Hugon, P.; Pagnier, I.; Robert, C.; Bittar, F.; Fournous, G.; Gimenez, G.; Maraninchi, M. Microbial culturomics: paradigm shift in the human gut microbiome study. Clinical Microbiology and Infection 2012, 18, 1185– 1193, DOI: 10.1111/1469-0691.12023Google Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1Gru7bP&md5=e7f57683de2adea0585015247a6dd5feMicrobial culturomics: paradigm shift in the human gut microbiome studyLagier, J.-C.; Armougom, F.; Million, M.; Hugon, P.; Pagnier, I.; Robert, C.; Bittar, F.; Fournous, G.; Gimenez, G.; Maraninchi, M.; Trape, J.-F.; Koonin, E. V.; La Scola, B.; Raoult, D.Clinical Microbiology and Infection (2012), 18 (12), 1185-1193CODEN: CMINFM; ISSN:1198-743X. (Wiley-Blackwell)Abstr. : Comprehensive detn. of the microbial compn. of the gut microbiota and the relationships with health and disease are major challenges in the 21st century. Metagenomic anal. of the human gut microbiota detects mostly uncultured bacteria. We studied stools from two lean Africans and one obese European, using 212 different culture conditions (microbial culturomics), and tested the colonies by using mass spectrometry and 16S rRNA amplification and sequencing. In parallel, we analyzed the same three samples by pyrosequencing 16S rRNA amplicons targeting the V6 region. The 32 500 colonies obtained by culturomics have yielded 340 species of bacteria from seven phyla and 117 genera, including two species from rare phyla (Deinococcus-Thermus and Synergistetes), five fungi, and a giant virus (Senegalvirus). The microbiome identified by culturomics included 174 species never described previously in the human gut, including 31 new species and genera for which the genomes were sequenced, generating c. 10 000 new unknown genes (ORFans), which will help in future mol. studies. Among these, the new species Microvirga massiliensis has the largest bacterial genome so far obtained from a human, and Senegalvirus is the largest virus reported in the human gut. Concurrent metagenomic anal. of the same samples produced 698 phylotypes, including 282 known species, 51 of which overlapped with the microbiome identified by culturomics. Thus, culturomics complements metagenomics by overcoming the depth bias inherent in metagenomic approaches.
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55Smith, P. M.; Howitt, M. R.; Panikov, N.; Michaud, M.; Gallini, C. A.; Bohlooly, Y. M.; Glickman, J. N.; Garrett, W. S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013, 341, 569– 573, DOI: 10.1126/science.1241165Google Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFyjsr3P&md5=8d7d91434f35758f764d89ab48527cacThe Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell HomeostasisSmith, Patrick M.; Howitt, Michael R.; Panikov, Nicolai; Michaud, Monia; Gallini, Carey Ann; Bohlooly-Y, Mohammad; Glickman, Jonathan N.; Garrett, Wendy S.Science (Washington, DC, United States) (2013), 341 (6145), 569-573CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Regulatory T cells (Tregs) that express the transcription factor Foxp3 are crit. for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific mols. that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, the authors posited that more prevalent factors exist that regulate the no. and function of colonic Tregs. The authors detd. that short-chain fatty acids, gut microbiota-derived bacterial fermn. products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. This study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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56Atarashi, K.; Tanoue, T.; Oshima, K.; Suda, W.; Nagano, Y.; Nishikawa, H.; Fukuda, S.; Saito, T.; Narushima, S.; Hase, K. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013, 500, 232– 236, DOI: 10.1038/nature12331Google Scholar56https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFShsbfJ&md5=ae3e310120459e75a80926aca55d4f2fTreg induction by a rationally selected mixture of Clostridia strains from the human microbiotaAtarashi, Koji; Tanoue, Takeshi; Oshima, Kenshiro; Suda, Wataru; Nagano, Yuji; Nishikawa, Hiroyoshi; Fukuda, Shinji; Saito, Takuro; Narushima, Seiko; Hase, Koji; Kim, Sangwan; Fritz, Joelle V.; Wilmes, Paul; Ueha, Satoshi; Matsushima, Kouji; Ohno, Hiroshi; Olle, Bernat; Sakaguchi, Shimon; Taniguchi, Tadatsugu; Morita, Hidetoshi; Hattori, Masahira; Honda, KenyaNature (London, United Kingdom) (2013), 500 (7461), 232-236CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases. Although numerous probiotic microorganisms have been identified, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiol. manner. Here the authors use a rational approach to isolate CD4+FOXP3+ regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human fecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in Treg-cell-inducing species. From these mice, the authors isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing Treg cell abundance and inducing important anti-inflammatory mols.-including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS)-in Treg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-β-rich environment to help expansion and differentiation of Treg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders.
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57Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J. R.; Pfeffer, K.; Coffer, P. J. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013, 504, 451– 455, DOI: 10.1038/nature12726Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOmtrrJ&md5=5df9a8c09b9b0e7f98522dfe16ef2711Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generationArpaia, Nicholas; Campbell, Clarissa; Fan, Xiying; Dikiy, Stanislav; van der Veeken, Joris; de Roos, Paul; Liu, Hui; Cross, Justin R.; Pfeffer, Klaus; Coffer, Paul J.; Rudensky, Alexander Y.Nature (London, United Kingdom) (2013), 504 (7480), 451-455CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the compn. of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the mol. cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, the authors reasoned that their metabolic byproducts are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. The authors tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. The authors found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermn., facilitated extrathymic generation of Treg cells. A boost in Treg-cell nos. after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the obsd. phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addn. to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. The results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
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58Donia, M. S.; Cimermancic, P.; Schulze, C. J.; Wieland Brown, L. C.; Martin, J.; Mitreva, M.; Clardy, J.; Linington, R. G.; Fischbach, M. A. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 2014, 158, 1402– 1414, DOI: 10.1016/j.cell.2014.08.032Google Scholar58https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFCgtLvP&md5=2588272748281d6e3f18966e2c74a702A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibioticsDonia, Mohamed S.; Cimermancic, Peter; Schulze, Christopher J.; Wieland Brown, Laura C.; Martin, John; Mitreva, Makedonka; Clardy, Jon; Linington, Roger G.; Fischbach, Michael A.Cell (Cambridge, MA, United States) (2014), 158 (6), 1402-1414CODEN: CELLB5; ISSN:0092-8674. (Cell Press)In complex biol. systems, small mols. often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, the authors identified 3118 small-mol. biosynthetic gene clusters (BGCs) in genomes of human-assocd. bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, they discovered that BGCs for a class of antibiotics in clin. trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. The authors purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. They demonstrated that lactocillin has potent antibacterial activity against a range of Gram-pos. vaginal pathogens, and they showed that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. These findings illustrate the widespread distribution of small-mol.-encoding BGCs in the human microbiome, and they demonstrate the bacterial prodn. of drug-like mols. in humans.
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59Lurie, I.; Yang, Y. X.; Haynes, K.; Mamtani, R.; Boursi, B. Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study. J. Clin. Psychiatry 2015, 76, 1522– 1528, DOI: 10.4088/JCP.15m09961Google Scholar59https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28visl2isg%253D%253D&md5=2d27297be935450c1c6fd82b0c0d25deAntibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control studyLurie Ido; Lurie Ido; Yang Yu-Xiao; Haynes Kevin; Mamtani Ronac; Boursi BenThe Journal of clinical psychiatry (2015), 76 (11), 1522-8 ISSN:.OBJECTIVE: Changes in the microbiota (dysbiosis) were suggested to increase the risk of several psychiatric conditions through neurologic, metabolic, and immunologic pathways. Our aim was to assess whether exposure to specific antibiotic groups increases the risk for depression, anxiety, or psychosis. METHOD: We conducted 3 nested case-control studies during the years 1995-2013 using a large population-based medical record database from the United Kingdom. The study included 202,974 patients with depression, 14,570 with anxiety, and 2,690 with psychosis and 803,961, 57,862, and 10,644 matched controls, respectively. Cases were defined as individuals aged 15-65 years with any medical Read code for depression, anxiety, or psychosis. Subjects with diagnosis-specific psychotropic prescriptions > 90 days before index date were excluded. For every case, 4 controls were selected using incidence density sampling, matching on age, sex, practice site, calendar time, and duration of follow-up before index date. The primary exposure of interest was therapy with 1 of 7 antibiotic classes > 1 year before index date. Odds ratios (ORs) and 95% CIs were calculated for the association between each psychiatric disorder and exposure to individual classes of antibiotics using conditional logistic regression analysis. The risk was adjusted for obesity, smoking history, alcohol consumption, socioeconomic status, and number of infectious events before diagnosis. RESULTS: Treatment with a single antibiotic course was associated with higher risk for depression with all antibiotic groups, with an adjusted OR (AOR) of 1.23 for penicillins (95% CI, 1.18-1.29) and 1.25 (95% CI, 1.15-1.35) for quinolones. The risk increased with recurrent antibiotic exposures to 1.40 (95% CI, 1.35-1.46) and 1.56 (95% CI, 1.46-1.65) for 2-5 and > 5 courses of penicillin, respectively. Similar association was observed for anxiety and was most prominent with exposures to penicillins and sulfonamides, with an AOR of 1.17 (95% CI, 1.01-1.36) for a single course of penicillin and 1.44 (95% CI, 1.18-1.75) for > 5 courses. There was no change in risk for psychosis with any antibiotic group. There was a mild increase in the risk of depression and anxiety with a single course of antifungals; however, there was no increase in risk with repeated exposures. CONCLUSION: Recurrent antibiotic exposure is associated with increased risk for depression and anxiety but not for psychosis.
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60Zheng, P.; Zeng, B.; Zhou, C.; Liu, M.; Fang, Z.; Xu, X.; Zeng, L.; Chen, J.; Fan, S.; Du, X. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol. Psychiatry 2016, 21, 786– 796, DOI: 10.1038/mp.2016.44Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmsVals78%253D&md5=58e19b9beef57cc353c806891f3ef2f0Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolismZheng, P.; Zeng, B.; Zhou, C.; Liu, M.; Fang, Z.; Xu, X.; Zeng, L.; Chen, J.; Fan, S.; Du, X.; Zhang, X.; Yang, D.; Yang, Y.; Meng, H.; Li, W.; Melgiri, N. D.; Licinio, J.; Wei, H.; Xie, P.Molecular Psychiatry (2016), 21 (6), 786-796CODEN: MOPSFQ; ISSN:1359-4184. (Nature Publishing Group)Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiol. of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clin. sampling, the gut microbiotic compns. of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metab. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metab.
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61Davis, D. J.; Hecht, P. M.; Jasarevic, E.; Beversdorf, D. Q.; Will, M. J.; Fritsche, K.; Gillespie, C. H. Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice. Brain, Behavior, and Immunity 2017, 59, 38– 48, DOI: 10.1016/j.bbi.2016.09.003Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsV2hu7bF&md5=f827c7e72227a384d1ab9d225bc3b2beSex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated miceDavis, Daniel J.; Hecht, Patrick M.; Jasarevic, Eldin; Beversdorf, David Q.; Will, Matthew J.; Fritsche, Kevin; Gillespie, Catherine H.Brain, Behavior, and Immunity (2017), 59 (), 38-48CODEN: BBIMEW; ISSN:0889-1591. (Elsevier)Dietary supplementation with the long-chain omega-3 polyunsatd. fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms assocd. with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a crit. role in regulating various biol. processes in the brain and may contribute to neuropsychiatric disease risk. The present study detd. the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28 days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24 h and 7 days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were obsd. in female mice. As the microbiota-brain-axis has been recently implicated in behavior, compn. of microbial communities were analyzed to examine if these sex-specific effects of DHA may be assocd. with changes in the gut microbiota (GM). Clear sex differences were obsd. with males and females showing distinct microbial compns. prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes obsd. in the male mice. Predictive metagenome anal. using PICRUSt was performed on the fecal samples collected from males and identified enrichment in functional KEGG pathway terms relevant to processes such as the biosynthesis of unsatd. fatty acids and antioxidant metab. These results indicate that DHA alters commensal community compn. and produces beneficial effects on anxiety and depressive-like behaviors in a sex-specific manner. The present study provides insight into the mechanistic role that gut microbes may play in the regulation of anxiety and depressive-like behaviors and how dietary intervention can modulate these effects.
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62Pasolli, E.; Asnicar, F.; Manara, S.; Zolfo, M.; Karcher, N.; Armanini, F.; Beghini, F.; Manghi, P.; Tett, A.; Ghensi, P. Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle. Cell 2019, 176, 649– 662.e20, DOI: 10.1016/j.cell.2019.01.001Google Scholar62https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVars7w%253D&md5=28875385d40b31967e02ad1538cf2c57Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and LifestylePasolli, Edoardo; Asnicar, Francesco; Manara, Serena; Zolfo, Moreno; Karcher, Nicolai; Armanini, Federica; Beghini, Francesco; Manghi, Paolo; Tett, Adrian; Ghensi, Paolo; Collado, Maria Carmen; Rice, Benjamin L.; DuLong, Casey; Morgan, Xochitl C.; Golden, Christopher D.; Quince, Christopher; Huttenhower, Curtis; Segata, NicolaCell (Cambridge, MA, United States) (2019), 176 (3), 649-662.e20CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many assocd. with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the av. mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-assocd. microbes, and allow better exploitation of metagenomic technologies.
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63Nayfach, S.; Shi, Z. J.; Seshadri, R.; Pollard, K. S.; Kyrpides, N. C. New insights from uncultivated genomes of the global human gut microbiome. Nature 2019, 568, 505– 510, DOI: 10.1038/s41586-019-1058-xGoogle Scholar63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXosVSgsbo%253D&md5=3a9d99af65b1dfad3b0e591fa19c8e16New insights from uncultivated genomes of the global human gut microbiomeNayfach, Stephen; Shi, Zhou Jason; Seshadri, Rekha; Pollard, Katherine S.; Kyrpides, Nikos C.Nature (London, United Kingdom) (2019), 568 (7753), 505-510CODEN: NATUAS; ISSN:0028-0836. (Nature Research)The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under lab. conditions. We address this problem by reconstructing 60,664 draft prokaryotic genomes from 3810 fecal metagenomes, from geog. and phenotypically diverse humans. These genomes provide ref. points for 2058 newly identified species-level operational taxonomic units (OTUs), which represents a 50% increase over the previously known phylogenetic diversity of sequenced gut bacteria. On av., the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual, and are enriched in humans from rural populations. A meta-anal. of clin. gut-microbiome studies pinpointed numerous disease assocns. for the newly identified OTUs, which have the potential to improve predictive models. Finally, our anal. revealed that uncultured gut species have undergone genome redn. that has resulted in the loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.
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64Pusceddu, M. M.; Barboza, M.; Schneider, M.; Stokes, P.; Sladek, J. A.; Torres-Fuentes, C.; Goldfild, L. R.; Gillis, S. E.; Brust-Mascher, I.; Rabasa, G. Nod-like receptors are critical for gut-brain axis signaling in mice. J. Physiol. 2019, 597, 5777– 5797, DOI: 10.1113/JP278640Google Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1arurzK&md5=a061ded6626d4888d224db082722f1d2Nod-like receptors are critical for gut-brain axis signalling in micePusceddu, Matteo M.; Barboza, Mariana; Keogh, Ciara E.; Schneider, Melinda; Stokes, Patricia; Sladek, Jessica A.; Kim, Hyun Jung D.; Torres-Fuentes, Cristina; Goldfild, Lily R.; Gillis, Shane E.; Brust-Mascher, Ingrid; Rabasa, Gonzalo; Wong, Kyle A.; Lebrilla, Carlito; Byndloss, Mariana X.; Maisonneuve, Charles; Baeumler, Andreas J.; Philpott, Dana J.; Ferrero, Richard L.; Barrett, Kim E.; Reardon, Colin; Gareau, Melanie G.Journal of Physiology (Oxford, United Kingdom) (2019), 597 (24), 5777-5797CODEN: JPHYA7; ISSN:1469-7793. (Wiley-Blackwell)Key points : ·Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. ·Nod-like receptors regulate central and peripheral serotonergic biol. ·Nod-like receptors are important for maintenance of gastrointestinal physiol. ·Intestinal epithelial cell expression of Nod1 receptors regulate behavior. Gut-brain axis signalling is crit. for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiol. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addn., NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress.
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65Pellegrini, C.; Antonioli, L.; Calderone, V.; Colucci, R.; Fornai, M.; Blandizzi, C. Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?. Prog. Neurobiol. 2020, 191, 101806, DOI: 10.1016/j.pneurobio.2020.101806Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVClsrrN&md5=81eaecf674dc6963a355a67b47845bb0Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communicationsPellegrini, Carolina; Antonioli, Luca; Calderone, Vincenzo; Colucci, Rocchina; Fornai, Matteo; Blandizzi, CorradoProgress in Neurobiology (Oxford, United Kingdom) (2020), 191 (), 101806CODEN: PGNBA5; ISSN:0301-0082. (Elsevier Ltd.)A review. Growing evidence highlights the relevance of microbiota-gut-brain axis in the maintenance of brain homeostasis as well as in the pathophysiol. of major neurol. and psychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD) and major depressive disorder (MDD). Of note, the nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-contg. protein 3 (NLRP3) inflammasome acts as a key player in both coordinating the host physiol. and shaping the peripheral and central immune/inflammatory responses in CNS diseases. The present review provides an overview of current knowledge on the role of microbiota-gut-inflammasome-brain axis in the major CNS diseases, including PD, AD, MS, ASD and MDD. In particular, though no direct and causal correlation among altered gut microbiota, NLRP3 activation and brain pathol. has been demonstrated and in-depth studies are needed in this setting, our purpose was to pave the way to a novel and pioneering perspective on the pathophysiol. of CNS disorders. Our intent was also to highlight and discuss whether alterations of microbiota-gut-inflammasome-brain axis support a holistic view of the pathophysiol. of CNS diseases, even though each disorder displays a different clin. picture.
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66Zhao, K.; Yao, M.; Zhang, X.; Xu, F.; Shao, X.; Wei, Y.; Wang, H. Flavonoids and intestinal microbes interact to alleviate depression. Journal of the Science of Food and Agriculture 2022, 102, 1311– 1318, DOI: 10.1002/jsfa.11578Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlCntbvF&md5=53b83d6529ef0b11cacf7b6b687c9fbbFlavonoids and intestinal microbes interact to alleviate depressionZhao, Ke; Yao, Mei; Zhang, Xin; Xu, Feng; Shao, Xingfeng; Wei, Yingying; Wang, HongfeiJournal of the Science of Food and Agriculture (2022), 102 (4), 1311-1318CODEN: JSFAAE; ISSN:0022-5142. (John Wiley & Sons Ltd.)A review. Flavonoids have a variety of biol. activities that are beneficial to human health. However, owing to low bioavailability, most flavonoids exert beneficial effects in the intestine through metab. by the flora into a variety of structurally different derivs. Also, flavonoids can modulate the type and structure of intestinal microorganisms to improve human health. It has been reported that the development of depression is accompanied by changes in the type and no. of intestinal microorganisms, and gut microbes can significantly improve depressive symptoms through the gut-brain axis. Therefore, the interaction between flavonoids and intestinal microbes to alleviate depression is discussed.
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67Segre, J. A. What does it take to satisfy Koch’s postulates two centuries later? Microbial genomics and Propionibacteria acnes. J. Invest. Dermatol. 2013, 133, 2141– 2142, DOI: 10.1038/jid.2013.260Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVykur%252FP&md5=165251fa065804d5cdc60736bf7e939eWhat Does It Take to Satisfy Koch's Postulates Two Centuries Later?: Microbial Genomics and Propionibacteria acnesSegre, Julia A.Journal of Investigative Dermatology (2013), 133 (9), 2141-2142CODEN: JIDEAE; ISSN:0022-202X. (Nature Publishing Group)For two centuries, Koch's postulates have set the gold std. for establishing the microbiol. etiol. of infection and disease. Genomic sequencing now brings finer resoln. to both bacterial strain variation and the host genetic state that may predispose to disease. In this issue of the JID, Fitz-Gibbons and colleagues present strain-based resoln. of Propionibacterium acnes and its assocn. with the common teenage malady acne vulgaris. Here I examine how Koch's postulates were envisioned and incorporate this finer resoln. of both host and microbial states.
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68Eiseman, B.; Silen, W.; Bascom, G. S.; Kauvar, A. J. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958, 44, 854– 859Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaG1M%252Fit1ShtA%253D%253D&md5=932cb97103c858a9f7c3112e2e61dca1Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitisEISEMAN B; SILEN W; BASCOM G S; KAUVAR A JSurgery (1958), 44 (5), 854-9 ISSN:0039-6060.There is no expanded citation for this reference.
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69Reyniers, J. A. The pure-culture concept and gnotobiotics. Ann. N.Y. Acad. Sci. 1959, 78, 3– 16, DOI: 10.1111/j.1749-6632.1959.tb53091.xGoogle ScholarThere is no corresponding record for this reference.
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70Schaedler, R. W.; Dubos, R.; Costello, R. ASSOCIATION OF GERMFREE MICE WITH BACTERIA ISOLATED FROM NORMAL MICE. J. Exp. Med. 1965, 122, 77– 82, DOI: 10.1084/jem.122.1.77Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaF2M7jtVWmsQ%253D%253D&md5=c693bd4d999907652054e8ac1c18c68cASSOCIATION OF GERMFREE MICE WITH BACTERIA ISOLATED FROM NORMAL MICESCHAEDLER R W; DUBS R; COSTELLO RThe Journal of experimental medicine (1965), 122 (), 77-82 ISSN:0022-1007.Germfree mice were given food contaminated with pure cultures of various bacterial species isolated from ordinary healthy mice. The cultures were given singly, or in association, or consecutively at weekly intervals. Whatever the technique of administration, the lactobacilli and anaerobic streptococci immediately established themselves throughout the gastrointestinal tract, and became closely associated with the walls of the organs. In contrast, the organisms of the bacteroides group were found in large numbers only in the large intestine. Within a week after exposure, the populations of these three bacterial species reached levels similar to those found in ordinary mice. They remained at these characteristic levels throughout the period of observation (several months). Their presence resulted in a progressive decrease in the size of the cecum which eventually became normal in gross appearance. Coliform bacilli multiplied extensively and persisted at high levels in all parts of the gastrointestinal tract of germfree mice, even after these had become colonized with lactobacilli, anaerobic streptococci and bacteroides. However, the coliform population fell precipitously within a few days after the animals were fed the intestinal contents of healthy pathogen-free mice.
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71Peppercorn, M. A.; Goldman, P. The Role of Intestinal Bacteria in the Metabolism of Salicylazosulfapyridine. Journal of Pharmacology and Experimental Therapeutics 1972, 181, 555– 562Google Scholar71https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE38Xks12qt7c%253D&md5=149105b21c094828504bc77d66df2b80Role of intestinal bacteria in the metabolism of salicylazosulfapyridinePeppercorn, Mark A.; Goldman, PeterJournal of Pharmacology and Experimental Therapeutics (1972), 181 (3), 555-62CODEN: JPETAB; ISSN:0022-3565.Following oral administration of salicylazosulfapyridine (I) [599-79-1] to normal rats, sulfapyridine [144-83-2], 5-aminosalicylate [89-57-6], and their N-acetyl derivs. were found in the excreta. No unchanged I was found. Pretreatment of the rats with neomycin [1404-04-2] in order to decrease intestinal microflora resulted in fecal recovery of >50% of the administered dose of I as unchanged I. Intestinal bacteria appear responsible for the initial reaction in I biotransformation and this raises questions concerning the amt. of unchanged I that reaches the presumed site of action in inflammatory disease of the lower intestine.
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72Stark, P. L.; Lee, A. The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. J. Med. Microbiol. 1982, 15, 189– 203, DOI: 10.1099/00222615-15-2-189Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL3s%252FlvFGqtw%253D%253D&md5=4c3b7442ffffe9234aebbad8912d627dThe microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of lifeStark P L; Lee AJournal of medical microbiology (1982), 15 (2), 189-203 ISSN:0022-2615.The succession of bacterial populations in the large bowel of seven breast-fed and seven formula-fed infants was examined during the first year of life. The composition of the intestinal microflora varied according to the infant's diet. During the first week of life breast-fed and formula-fed infants were colonised by enterobacteria and enterococci followed by bifidobacteria, Bacteroides spp., clostridia and anaerobic streptococci. From week 4 until solid foods were given, breast-fed babies had a simple flora consisting of bifidobacteria and relatively few enterobacteria and enterococci. Formula-fed babies during the corresponding period were more often colonised by other anaerobes in addition to bifidobacteria and had higher counts of facultatively anaerobic bacteria. The introduction of solid food to the breast-fed infants caused a major disturbance in the microbial ecology of the large bowel as counts of enterobacteria and enterococci rose sharply and colonisation by Bacteroides spp., clostridia and anaerobic streptococci occurred. This was not observed when formula-fed infants began to take solids; instead, counts of facultative anaerobes remained high while colonisation by anaerobes other than bifidobacteria continued. At 12 months, the anaerobic bacterial populations of the large bowel of breast-fed and formula-fed infants were beginning to resemble those of adults in number and composition and there was a corresponding decrease in the number of facultative anaerobes. These changes are discussed in relation to changes in susceptibility to gastro-intestinal infection.
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73Fleischmann, R. D.; Adams, M. D.; White, O.; Clayton, R. A.; Kirkness, E. F.; Kerlavage, A. R.; Bult, C. J.; Tomb, J. F.; Dougherty, B. A.; Merrick, J. M. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995, 269, 496– 512, DOI: 10.1126/science.7542800Google Scholar73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXntF2ksLc%253D&md5=471dc5b1db156773d4883e41b78ece77Whole-genome random sequencing and assembly of Haemophilus influenzae RdFleischmann, Robert D.; Adams, Mark D.; White, Owen; Clayton, Rebecca A.; Kirkness, Ewen F.; Kerlavage, Anthony R.; Bult, Carol J.; Tomb, Jean-Francois; Dougherty, Brian A.; et al.Science (Washington, D. C.) (1995), 269 (5223), 496-8, 507-12CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)An approach for genome anal. based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genomes maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession no. L42023) represents the only complete genome sequence from a free-living organism.
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74Wilson, K. H.; Blitchington, R. B. Human colonic biota studied by ribosomal DNA sequence analysis. Appl. Environ. Microbiol. 1996, 62, 2273– 2278, DOI: 10.1128/aem.62.7.2273-2278.1996Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XjvFGntro%253D&md5=a29cae5d95717df891d1b69cd23dcf93Human colonic biota studied by ribosomal DNA sequence analysisWilson, Kenneth H.; Blitchington, Rhonda B.Applied and Environmental Microbiology (1996), 62 (7), 2273-2278CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)Human colonic biota is a complex microbial ecosystem that serves as a host defense. Unlike most microbial ecosystems, its compn. has been studied extensively by relatively efficient culture methods. The authors have compared an established culture-based method with direct amplification and partial sequencing of cloned 16S rRNA genes from a human fecal specimen. Nine cycles of PCR were also compared with 35 cycles. Colonies and cloned amplicons were classified by comparing their ribosomal DNA (rDNA; DNA coding for rRNA) sequences with rDNA sequences of known phylogeny. Quant. culture recovered 58% of the microscopic count. The 48 colonies identified gave 21 rDNA sequences; it was estd. that 72% of the rDNA sequences from the total population of culturable cells would match these 21 sampled sequences (72% coverage). Fifty 9-cycle clones gave 27 sequences and 59% coverage of cloned rDNAs. Thirty-nine rDNAs cloned after 35 cycles of PCR gave 13 sequences for 74% coverage. Thus, the representation of the ecosystem after 35 cycles of PCR was distorted and lacked diversity. However, when the no. of temp. cycles was minimized, biodiversity was preserved, and there was good agreement between culturing bacteria and sampling rDNA directly.
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75Guarner, F.; Malagelada, J. R. Gut flora in health and disease. Lancet 2003, 361, 512– 519, DOI: 10.1016/S0140-6736(03)12489-0Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3s%252FntlKltg%253D%253D&md5=fd95e325ed4ca919a4d28659eb506038Gut flora in health and diseaseGuarner Francisco; Malagelada Juan-RLancet (London, England) (2003), 361 (9356), 512-9 ISSN:0140-6736.The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.
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76Rakoff-Nahoum, S.; Paglino, J.; Eslami-Varzaneh, F.; Edberg, S.; Medzhitov, R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118, 229– 241, DOI: 10.1016/j.cell.2004.07.002Google Scholar76https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtlKntrg%253D&md5=08ed04f1969160743c82bae2b70a201bRecognition of commensal microflora by Toll-like receptors is required for intestinal homeostasisRakoff-Nahoum, Seth; Paglino, Justin; Eslami-Varzaneh, Fatima; Edberg, Stephen; Medzhitov, RuslanCell (Cambridge, MA, United States) (2004), 118 (2), 229-241CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is crit. for the protection against gut injury and assocd. mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
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77Mazmanian, S. K.; Liu, C. H.; Tzianabos, A. O.; Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 2005, 122, 107– 118, DOI: 10.1016/j.cell.2005.05.007Google Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmsFeiurw%253D&md5=029fa2f2e90305138740c220055e4f15An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune systemMazmanian, Sarkis K.; Liu, Cui Hua; Tzianabos, Arthur O.; Kasper, Dennis L.Cell (Cambridge, MA, United States) (2005), 122 (1), 107-118CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial mols. mediating symbiosis remain undefined. Here the authors show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and phys. maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and TH1/TH2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunol. functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine prodn. These findings provide a mol. basis for host-bacterial symbiosis and reveal the archetypal mol. of commensal bacteria that mediates development of the host immune system.
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78Turnbaugh, P. J.; Ley, R. E.; Mahowald, M. A.; Magrini, V.; Mardis, E. R.; Gordon, J. I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027– 1031, DOI: 10.1038/nature05414Google Scholar78https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjslWgurs%253D&md5=628d0c9769232cc726ebf8f2d19068eeAn obesity-associated gut microbiome with increased capacity for energy harvestTurnbaugh, Peter J.; Ley, Ruth E.; Mahowald, Michael A.; Magrini, Vincent; Mardis, Elaine R.; Gordon, Jeffrey I.Nature (London, United Kingdom) (2006), 444 (7122), 1027-1031CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is assocd. with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through meta-genomic and biochem. analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an addnl. contributing factor to the pathophysiol. of obesity.
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79Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C. P. M.; Alou, M. T.; Daillère, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M. P. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science 2018, 359, 91– 97, DOI: 10.1126/science.aan3706Google Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXjslOrsw%253D%253D&md5=a095f1934782cd73323256ab75957462Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumorsRouty, Bertrand; Le Chatelier, Emmanuelle; Derosa, Lisa; Duong, Connie P. M.; Alou, Maryam Tidjani; Daillere, Romain; Fluckiger, Aurelie; Messaoudene, Meriem; Rauber, Conrad; Roberti, Maria P.; Fidelle, Marine; Flament, Caroline; Poirier-Colame, Vichnou; Opolon, Paule; Klein, Christophe; Iribarren, Kristina; Mondragon, Laura; Jacquelot, Nicolas; Qu, Bo; Ferrere, Gladys; Clemenson, Celine; Mezquita, Laura; Masip, Jordi Remon; Naltet, Charles; Brosseau, Solenn; Kaderbhai, Coureche; Richard, Corentin; Rizvi, Hira; Levenez, Florence; Galleron, Nathalie; Quinquis, Benoit; Pons, Nicolas; Ryffel, Bernhard; Minard-Colin, Veronique; Gonin, Patrick; Soria, Jean-Charles; Deutsch, Eric; Loriot, Yohann; Ghiringhelli, Francois; Zalcman, Gerard; Goldwasser, Francois; Escudier, Bernard; Hellmann, Matthew D.; Eggermont, Alexander; Raoult, Didier; Albiges, Laurence; Kroemer, Guido; Zitvogel, LaurenceScience (Washington, DC, United States) (2018), 359 (6371), 91-97CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clin. responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome compn. Antibiotics inhibited the clin. benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clin. responses to ICIs and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.
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80Matson, V.; Fessler, J.; Bao, R.; Chongsuwat, T.; Zha, Y.; Alegre, M. L.; Luke, J. J.; Gajewski, T. F. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018, 359, 104– 108, DOI: 10.1126/science.aao3290Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXjslOksg%253D%253D&md5=961e9b039d3cdb440d618640ad218dadThe commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patientsMatson, Vyara; Fessler, Jessica; Bao, Riyue; Chongsuwat, Tara; Zha, Yuanyuan; Alegre, Maria-Luisa; Luke, Jason J.; Gajewski, Thomas F.Science (Washington, DC, United States) (2018), 359 (6371), 104-108CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential compn. of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclin. mouse models. The authors analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S rRNA gene sequencing, metagenomic shotgun sequencing, and quant. polymerase chain reaction for selected bacteria. A significant assocn. was obsd. between commensal microbial compn. and clin. response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. The authors' results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.
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81Belizário, J. E.; Napolitano, M. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front. Microbiol. 2015, 6, 1050, DOI: 10.3389/fmicb.2015.01050Google Scholar81https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28zlslWmtA%253D%253D&md5=9c50c0d119d45e1f45a9d16073e0eda2Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approachesBelizario Jose E; Napolitano MauroFrontiers in microbiology (2015), 6 (), 1050 ISSN:1664-302X.The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.
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82Rinninella, E.; Raoul, P.; Cintoni, M.; Franceschi, F.; Miggiano, G. A. D.; Gasbarrini, A.; Mele, M. C. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms 2019, 7, 14, DOI: 10.3390/microorganisms7010014Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1ShsbjF&md5=388f6272007c7539cbd95a26581cabefWhat is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseasesRinninella, Emanuele; Raoul, Pauline; Cintoni, Marco; Franceschi, Francesco; Miggiano, Giacinto Abele Donato; Gasbarrini, Antonio; Mele, Maria CristinaMicroorganisms (2019), 7 (1), 14CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metab., maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human's gut microbiota are shaped in early life as their compn. depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota compn. since it is different for each individual. However, a healthy host-microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is assocd. not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurol. disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota compn. should be useful in developing promising therapeutic interventions.
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83Cresci, G. A. M.; Izzo, K. Chapter 4 - Gut Microbiome. In Adult Short Bowel Syndrome; Corrigan, M. L., Roberts, K., Steiger, E., Eds.; Academic Press, 2019; pp 45– 54.Google ScholarThere is no corresponding record for this reference.
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84CAS Content Collection. https://www.cas.org/about/cas-content (accessed January 18, 2023).Google ScholarThere is no corresponding record for this reference.
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85Kho, Z. Y.; Lal, S. K. The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Front. Microbiol. 2018, 9, 1835, DOI: 10.3389/fmicb.2018.01835Google Scholar85https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3islyitA%253D%253D&md5=b3201161709507f19e152a0a0481abf2The Human Gut Microbiome - A Potential Controller of Wellness and DiseaseKho Zhi Y; Lal Sunil KFrontiers in microbiology (2018), 9 (), 1835 ISSN:1664-302X.Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
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86Sankar, S. A.; Lagier, J. C.; Pontarotti, P.; Raoult, D.; Fournier, P. E. The human gut microbiome, a taxonomic conundrum. Syst. Appl. Microbiol 2015, 38, 276– 286, DOI: 10.1016/j.syapm.2015.03.004Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXls1GktL0%253D&md5=c6f708049d43e2ba4bb0111faae14855The human gut microbiome, a taxonomic conundrumSankar, Senthil Alias; Lagier, Jean-Christophe; Pontarotti, Pierre; Raoult, Didier; Fournier, Pierre-EdouardSystematic and Applied Microbiology (2015), 38 (4), 276-286CODEN: SAMIDF; ISSN:0723-2020. (Elsevier GmbH)From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geog. origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested assocns. between specific gut microbiota compns. and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health.
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87Manson, J. M.; Rauch, M.; Gilmore, M. S. The Commensal Microbiology of the Gastrointestinal Tract. In GI Microbiota and Regulation of the Immune System; Huffnagle, G. B., Noverr, M. C., Eds.; Landes Bioscience and Springer Science+Business Media, LLC: New York, 2008; pp 15– 28.Google ScholarThere is no corresponding record for this reference.
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88Kim, D.-H. Gut Microbiota-Mediated Drug-Antibiotic Interactions. Drug Metab. Dispos. 2015, 43, 1581– 1589, DOI: 10.1124/dmd.115.063867Google Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1Sgu7fF&md5=d479e92f2c129a8ded40ea9b9c743555Gut microbiota-mediated drug-antibiotic interactionsKim, Dong-HyunDrug Metabolism & Disposition (2015), 43 (10), 1581-1589CODEN: DMDSAI; ISSN:1521-009X. (American Society for Pharmacology and Experimental Therapeutics)Xenobiotic metab. involves the biochem. modification of drugs and phytochems. in living organisms, including humans and other animals. In the intestine, the gut microbiota catalyzes the conversion of hydrophilic drugs into absorbable, hydrophobic compds. through hydroxyzation and redn. Drugs and phytochems. are transformed into bioactive (sulfasalazine, lovastatin, and ginsenoside Rb1), bioinactive (chloramphenicol, ranitidine, and metronidazole), and toxic metabolites (nitrazepam), thus affecting the pharmacokinetics of the original compds. Antibiotics suppress the activities of drug-metabolizing enzymes by inhibiting the proliferation of gut microbiota. Antibiotic treatment might influence xenobiotic metabs. more extensively and potently than previously recognized and reduce gut microbiotamediated transformation of orally administered drugs, thereby altering the systemic concns. of intact drugs, their metabolites, or both. This review describes the effects of antibiotics on the metab. of drugs and phytochems. by the gut microbiota.
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89Deng, P.; Swanson, K. S. Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges. Br. J. Nutr. 2015, 113 (Suppl), S6– 17, DOI: 10.1017/S0007114514002943Google Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjtlSlu7w%253D&md5=3d61cf86b3eea97f65aacc02f12e8306Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challengesDeng, Ping; Swanson, Kelly S.British Journal of Nutrition (2015), 113 (S1), S6-S17CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)A review. High-throughput DNA sequencing techniques allow for the identification and characterization of microbes and their genes (microbiome). Using these new techniques, microbial populations in several niches of the human body, including the oral and nasal cavities, skin, urogenital tract and gastrointestinal tract, have been described recently. Very little data on the microbiome of companion animals exist, and most of the data have been derived from the anal. of the faeces of healthy lab. animals. High-throughput assays provide opportunities to study the complex and dense populations of the gut microbiota, including bacteria, archaea, fungi, protozoa and viruses. Our lab. and others have recently described the predominant microbial taxa and genes of healthy dogs and cats and how these respond to dietary interventions. In general, faecal microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) and functional capacity (e.g. major functional groups related to carbohydrate, protein, DNA and vitamin metab.; virulence factors; and cell wall and capsule) of the canine and feline gut are similar to those of the human gut. Initial sequencing projects have provided a glimpse of the microbial super-organism that exists within the canine and feline gut, but leaves much to be explored and discovered. As DNA provides information only about potential functions, studies that focus on the microbial transcriptome, metabolite profiles, and how microbiome changes affect host physiol. and health are clearly required. Future studies must det. how diet compn., antibiotics and other drug therapies, breed and disease affect or are affected by the gut microbiome and how this information may be used to improve diets, identify disease biomarkers and develop targeted disease therapies.
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90Nardone, G.; Compare, D. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?. United European Gastroenterol J. 2015, 3, 255– 260, DOI: 10.1177/2050640614566846Google Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlyitr3O&md5=a6730cf0d3575ef11cdbeb4572753272The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?Nardone, Gerardo; Compare, DeboraUnited European Gastroenterology Journal (2015), 3 (3), 255-260CODEN: UEGJAZ; ISSN:2050-6414. (Sage Publications Ltd.)Introduction: Although long thought to be a sterile organ, due to its acid prodn., the human stomach holds a core microbiome. Aim: To provide an update of findings related to gastric microbiota and its link with gastric diseases. Methods: We conducted a systematic review of the literature. Results: The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the compn. of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual's risk of gastric disease, including gastric cancer. Conclusions: The maintenance of bacterial homeostasis could be essential for the stomach's health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task.
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91Ghosh, S.; Pramanik, S. Structural diversity, functional aspects and future therapeutic applications of human gut microbiome. Arch. Microbiol. 2021, 203, 5281– 5308, DOI: 10.1007/s00203-021-02516-yGoogle Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvVaju77K&md5=bf4e1881a45d2b81d40bc769418a59aaStructural diversity, functional aspects and future therapeutic applications of human gut microbiomeGhosh, Soma; Pramanik, SreemantaArchives of Microbiology (2021), 203 (9), 5281-5308CODEN: AMICCW; ISSN:0302-8933. (Springer)Abstr.: The research on human gut microbiome, regarded as the black box of the human body, is still at the stage of infancy as the functional properties of the complex gut microbiome have not yet been understood. Ongoing metagenomic studies have deciphered that the predominant microbial communities belong to eubacterial phyla Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Cyanobacteria, Verrucomicrobia and archaebacterial phylum Euryarchaeota. The indigenous commensal microbial flora prevents opportunistic pathogenic infection and play undeniable roles in digestion, metabolite and signaling mol. prodn. and controlling host's cellular health, immunity and neuropsychiatric behavior. Besides maintaining intestinal health via short-chain fatty acid (SCFA) prodn., gut microbes also aid in neuro-immuno-endocrine modulatory mol. prodn., immune cell differentiation and glucose and lipid metab. Interdependence of diet and intestinal microbial diversity suggests the effectiveness of pre- and pro-biotics in maintenance of gut and systemic health. Several companies worldwide have started potentially exploiting the microbial contribution to human health and have translated their use in disease management and therapeutic applications. The present review discusses the vast diversity of microorganisms playing intricate roles in human metab. The contribution of the intestinal microbiota to regulate systemic activities including gut-brain-immunity crosstalk has been focused. To the best of our knowledge, this review is the first of its kind to collate and discuss the companies worldwide translating the multi-therapeutic potential of human intestinal microbiota, based on the multi-omics studies, i.e. metagenomics and metabolomics, as ready solns. for several metabolic and systemic disorders. Graphic abstr.: [graphic not available: see fulltext].
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92Leser, T. D.; Mo̷lbak, L. Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the host. Environ. Microbiol. 2009, 11, 2194– 2206, DOI: 10.1111/j.1462-2920.2009.01941.xGoogle Scholar92https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXht1GntrbP&md5=27a4195b0faaab89256c21d3b1bc4e33Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the hostLeser, Thomas D.; Moelbak, LarsEnvironmental Microbiology (2009), 11 (9), 2194-2206CODEN: ENMIFM; ISSN:1462-2912. (Wiley-Blackwell)A review. Mammals live in a homeostatic symbiosis with their gastrointestinal microbiota. The mammalian host provides the microbiota with nutrients and a stable environment; whereas the microbiota helps shaping the host's gut mucosa and provides nutritional contributions. Microorganisms start colonizing the gut immediately after birth followed by a succession of populations until a stable, adult microbiota has been established. However, physiol. conditions differ substantially among locations in the gut and det. bacterial d. and diversity. While Firmicutes and Bacteroidetes dominate the gut microbiota in all mammals, the bacterial genera and species diversity is huge and reflects mammalian phylogeny. The main function of the gastrointestinal epithelium is to absorb nutrients and to retain water and electrolytes, yet at the same time it is an efficient barrier against harmful compds. and microorganisms, and is able to neutralize antagonists coincidentally breaching the barrier. These processes are influenced by the microbiota, which modify epithelial expression of genes involved in nutrient uptake and metab., mucosal barrier function, xenobiotic metab., enteric nervous system and motility, hormonal and maturational responses, angiogenesis, cytoskeleton and extracellular matrix, signal transduction, and general cellular functions. Whereas such effects are local at the gut epithelium they may eventually have systemic consequences, e.g. on body wt. and compn.
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93Linares, D. M.; Ross, P.; Stanton, C. Beneficial Microbes: The pharmacy in the gut. Bioengineered 2016, 7, 11– 20, DOI: 10.1080/21655979.2015.1126015Google Scholar93https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvFOjsb0%253D&md5=7070a47d0046a1853be4e8dceedf69aeBeneficial Microbes: The pharmacy in the gutLinares, Daniel M.; Ross, Paul; Stanton, CatherineBioengineered (2016), 7 (1), 11-20CODEN: BIOEGL; ISSN:2165-5987. (Taylor & Francis, Inc.)The scientific evidence supporting the gut microbiome in relation to health maintenance and links with various disease states afflicting humans, from metabolic to mental health, has grown dramatically in the last few years. Strategies addressing the pos. modulation of microbiome functionality assocd. with these disorders offer huge potential to the food and pharmaceutical industries to innovate and provide therapeutic solns. to many of the health issues affecting modern society. Such strategies may involve the use of probiotics and prebiotics as nutritional adjunct therapies. Probiotics are generally recognized to be a good form of therapy to keep harmful, intestinal microorganisms in check, aid digestion and nutrient absorption, and contribute to immune function. Probiotics are reported to improve microbial balance in the intestinal tract and promote the return to a baseline microbial community following a perturbing event (dysbiosis) such as antibiotic therapy. Prebiotics are selectively fermented ingredients that allow specific changes, both in the compn. and/or activity in the gastrointestinal microflora, which confers benefits upon host well-being and health.
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94Shah, H. N.; Olsen, I.; Bernard, K.; Finegold, S. M.; Gharbia, S.; Gupta, R. S. Approaches to the study of the systematics of anaerobic, Gram-negative, non-sporeforming rods: Current status and perspectives. Anaerobe 2009, 15, 179– 194, DOI: 10.1016/j.anaerobe.2009.08.003Google Scholar94https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtlChurfL&md5=7db4a2390acafa75bfbdaab154fa032fApproaches to the study of the systematics of anaerobic, Gram-negative, non-spore forming rods: Current status and perspectivesShah, Haroun N.; Olsen, Ingar; Bernard, Kathy; Finegold, Sydney M.; Gharbia, Saheer; Gupta, Radhey S.Anaerobe (2009), 15 (5), 179-194CODEN: ANAEF8; ISSN:1075-9964. (Elsevier Ltd.)A review. The present article gives an overview of recent taxonomic changes among the Gram-neg., anaerobic rods, briefly highlighting areas where the biol. and ecol. have a bearing on recent nomenclatorial changes. The focus is among the genera Bacteroides, Prevotella, Porphyromonas, Leptotrichia, Dysgonomonas, Fusobacterium and the Synergistes group and addnl. demonstrates the value of conserved indels and group-specific proteins for identifying and circumscribing many of these taxa and the Bacteroidetes-Chlorobi species in general.
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95Thomas, F.; Hehemann, J.-H.; Rebuffet, E.; Czjzek, M.; Michel, G. Environmental and Gut Bacteroidetes: The Food Connection. Front. Microbiol. 2011, 2, 93, DOI: 10.3389/fmicb.2011.00093Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MnntlGnug%253D%253D&md5=0261db88b24d98213748c16711290e03Environmental and gut bacteroidetes: the food connectionThomas Francois; Hehemann Jan-Hendrik; Rebuffet Etienne; Czjzek Mirjam; Michel GurvanFrontiers in microbiology (2011), 2 (), 93 ISSN:.Members of the diverse bacterial phylum Bacteroidetes have colonized virtually all types of habitats on Earth. They are among the major members of the microbiota of animals, especially in the gastrointestinal tract, can act as pathogens and are frequently found in soils, oceans and freshwater. In these contrasting ecological niches, Bacteroidetes are increasingly regarded as specialists for the degradation of high molecular weight organic matter, i.e., proteins and carbohydrates. This review presents the current knowledge on the role and mechanisms of polysaccharide degradation by Bacteroidetes in their respective habitats. The recent sequencing of Bacteroidetes genomes confirms the presence of numerous carbohydrate-active enzymes covering a large spectrum of substrates from plant, algal, and animal origin. Comparative genomics reveal specific Polysaccharide Utilization Loci shared between distantly related members of the phylum, either in environmental or gut-associated species. Moreover, Bacteroidetes genomes appear to be highly plastic and frequently reorganized through genetic rearrangements, gene duplications and lateral gene transfers (LGT), a feature that could have driven their adaptation to distinct ecological niches. Evidence is accumulating that the nature of the diet shapes the composition of the intestinal microbiota. We address the potential links between gut and environmental bacteria through food consumption. LGT can provide gut bacteria with original sets of utensils to degrade otherwise refractory substrates found in the diet. A more complete understanding of the genetic gateways between food-associated environmental species and intestinal microbial communities sheds new light on the origin and evolution of Bacteroidetes as animals' symbionts. It also raises the question as to how the consumption of increasingly hygienic and processed food deprives our microbiota from useful environmental genes and possibly affects our health.
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96McKee, L. S.; La Rosa, S. L.; Westereng, B.; Eijsink, V. G.; Pope, P. B.; Larsbrink, J. Polysaccharide degradation by the Bacteroidetes: mechanisms and nomenclature. Environ. Microbiol. Rep. 2021, 13, 559– 581, DOI: 10.1111/1758-2229.12980Google Scholar96https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhslylt7fK&md5=62fc8423173fefa31728f517b684318cPolysaccharide degradation by the Bacteroidetes: mechanisms and nomenclatureMcKee, Lauren S.; La Rosa, Sabina Leanti; Westereng, Bjoerge; Eijsink, Vincent G.; Pope, Phillip B.; Larsbrink, JohanEnvironmental Microbiology Reports (2021), 13 (5), 559-581CODEN: EMRNAG; ISSN:1758-2229. (Wiley-Blackwell)The Bacteroidetes phylum is renowned for its ability to degrade a wide range of complex carbohydrates, a trait that has enabled its dominance in many diverse environments. The best studied species inhabit the human gut microbiome and use polysaccharide utilization loci (PULs), discrete genetic structures that encode proteins involved in the sensing, binding, deconstruction, and import of target glycans. In many environmental species, polysaccharide degrdn. is tightly coupled to the phylum-exclusive type IX secretion system (T9SS), which is used for the secretion of certain enzymes and is linked to gliding motility. In addn., within specific species these two adaptive systems (PULs and T9SS) are intertwined, with PUL-encoded enzymes being secreted by the T9SS. Here, we discuss the most noteworthy PUL and non-PUL mechanisms that confer specific and rapid polysaccharide degrdn. capabilities to the Bacteroidetes in a range of environments. We also acknowledge that the literature showcasing examples of PULs is rapidly expanding and developing a set of assumptions that can be hard to track back to original findings. Therefore, we present a simple universal description of conserved PUL functions and how they are detd., while proposing a common nomenclature describing PULs and their components, to simplify discussion and understanding of PUL systems.
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97Ludwig, W.; Schleifer, K.-H.; Whitman, W. B. Revised road map to the phylum Firmicutes. In Bergey’s Manual of Systematic Bacteriology: Vol. Three The Firmicutes; De Vos, P., Garrity, G. M., Jones, D., Krieg, N. R., Ludwig, W., Rainey, F. A., Schleifer, K.-H., Whitman, W. B., Eds.; Springer New York: New York, 2009; pp 1– 13.Google ScholarThere is no corresponding record for this reference.
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98Yang, M.; Gu, Y.; Li, L.; Liu, T.; Song, X.; Sun, Y.; Cao, X.; Wang, B.; Jiang, K.; Cao, H. Bile Acid–Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside. Nutrients 2021, 13, 3143, DOI: 10.3390/nu13093143Google Scholar98https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVKgtrfN&md5=05bbf4ed3aea2831c978ef4758623890Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to BedsideYang, Min; Gu, Yu; Li, Lingfeng; Liu, Tianyu; Song, Xueli; Sun, Yue; Cao, Xiaocang; Wang, Bangmao; Jiang, Kui; Cao, HailongNutrients (2021), 13 (9), 3143CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial compn. marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metab.) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concn. of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.
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99Barka, E. A.; Vatsa, P.; Sanchez, L.; Gaveau-Vaillant, N.; Jacquard, C.; Klenk, H.-P.; Clément, C.; Ouhdouch, Y.; Wezel, G. P. v. Taxonomy, Physiology, and Natural Products of Actinobacteria. Microbiology and Molecular Biology Reviews 2016, 80, 1– 43, DOI: 10.1128/MMBR.00019-15Google Scholar99https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vls1Sjtg%253D%253D&md5=dac99309cc12275c1dbbc27e457fd9ffTaxonomy, Physiology, and Natural Products of ActinobacteriaBarka Essaid Ait; Vatsa Parul; Sanchez Lisa; Gaveau-Vaillant Nathalie; Jacquard Cedric; Clement Christophe; Meier-Kolthoff Jan P; Klenk Hans-Peter; Ouhdouch Yder; van Wezel Gilles PMicrobiology and molecular biology reviews : MMBR (2016), 80 (1), 1-43 ISSN:.Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum.
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100Hidalgo-Cantabrana, C.; Delgado, S.; Ruiz, L.; Ruas-Madiedo, P.; Sánchez, B.; Margolles, A. Bifidobacteria and Their Health-Promoting Effects. Microbiol Spectr 2017, 5, 5.3.21, DOI: 10.1128/microbiolspec.BAD-0010-2016Google ScholarThere is no corresponding record for this reference.
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101Stackebrandt, E.; Murray, R. G. E.; Trüper, H. G. Proteobacteria classis nov., a Name for the Phylogenetic Taxon That Includes the “Purple Bacteria and Their Relatives. International Journal of Systematic and Evolutionary Microbiology 1988, 38, 321– 325, DOI: 10.1099/00207713-38-3-321Google ScholarThere is no corresponding record for this reference.
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102Rizzatti, G.; Lopetuso, L. R.; Gibiino, G.; Binda, C.; Gasbarrini, A. Proteobacteria: A Common Factor in Human Diseases. BioMed. Research International 2017, 2017, 9351507, DOI: 10.1155/2017/9351507Google Scholar102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MzgsVKgsg%253D%253D&md5=ff061232dd3e1d205818520859b76722Proteobacteria: A Common Factor in Human DiseasesRizzatti G; Lopetuso L R; Gibiino G; Binda C; Gasbarrini ABioMed research international (2017), 2017 (), 9351507 ISSN:.Microbiota represents the entire microbial community present in the gut host. It serves several functions establishing a mutualistic relation with the host. Latest years have seen a burst in the number of studies focusing on this topic, in particular on intestinal diseases. In this scenario, Proteobacteria are one of the most abundant phyla, comprising several known human pathogens. This review highlights the latest findings on the role of Proteobacteria not only in intestinal but also in extraintestinal diseases. Indeed, an increasing amount of data identifies Proteobacteria as a possible microbial signature of disease. Several studies demonstrate an increased abundance of members belonging to this phylum in such conditions. Major evidences currently involve metabolic disorders and inflammatory bowel disease. However, more recent studies suggest a role also in lung diseases, such as asthma and chronic obstructive pulmonary disease, but evidences are still scant. Notably, all these conditions are sustained by various degree of inflammation, which thus represents a core aspect of Proteobacteria-related diseases.
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103Lee, K.-C.; Webb, R. I.; Janssen, P. H.; Sangwan, P.; Romeo, T.; Staley, J. T.; Fuerst, J. A. Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes. BMC Microbiol. 2009, 9, 5, DOI: 10.1186/1471-2180-9-5Google Scholar103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M7msFyitQ%253D%253D&md5=d528d371ef74f6683ff411a93595b264Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum PlanctomycetesLee Kuo-Chang; Webb Richard I; Janssen Peter H; Sangwan Parveen; Romeo Tony; Staley James T; Fuerst John ABMC microbiology (2009), 9 (), 5 ISSN:.BACKGROUND: The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter, includes species with genes homologous to those encoding eukaryotic tubulins. A significant superphylum relationship of Verrucomicrobia with members of phylum Planctomycetes possessing a unique compartmentalized cell plan, and members of the phylum Chlamydiae including human pathogens with a complex intracellular life cycle, has been proposed. Based on the postulated superphylum relationship, we hypothesized that members of the two separate phyla Planctomycetes and Verrucomicrobia might share a similar ultrastructure plan differing from classical prokaryote organization. RESULTS: The ultrastructure of cells of four members of phylum Verrucomicrobia - Verrucomicrobium spinosum, Prosthecobacter dejongeii, Chthoniobacter flavus, and strain Ellin514 - was examined using electron microscopy incorporating high-pressure freezing and cryosubstitution. These four members of phylum Verrucomicrobia, representing 3 class-level subdivisions within the phylum, were found to possess a compartmentalized cell plan analogous to that found in phylum Planctomycetes. Like all planctomycetes investigated, they possess a major pirellulosome compartment containing a condensed nucleoid and ribosomes surrounded by an intracytoplasmic membrane (ICM), as well as a ribosome-free paryphoplasm compartment between the ICM and cytoplasmic membrane. CONCLUSION: A unique compartmentalized cell plan so far found among Domain Bacteria only within phylum Planctomycetes, and challenging our concept of prokaryote cell plans, has now been found in a second phylum of the Domain Bacteria, in members of phylum Verrucomicrobia. The planctomycete cell plan thus occurs in at least two distinct phyla of the Bacteria, phyla which have been suggested from other evidence to be related phylogenetically in the proposed PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) superphylum. This planctomycete cell plan is present in at least 3 of 6 subdivisions of Verrucomicrobia, suggesting that the common ancestor of the verrucomicrobial phylum was also compartmentalized and possessed such a plan. The presence of this compartmentalized cell plan in both phylum Planctomycetes and phylum Verrucomicrobia suggest that the last common ancestor of these phyla was also compartmentalized.
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104Rappé, M. S.; Giovannoni, S. J. The Uncultured Microbial Majority. Annu. Rev. Microbiol. 2003, 57, 369– 394, DOI: 10.1146/annurev.micro.57.030502.090759Google Scholar104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXptFWlsr8%253D&md5=8f5a003db3f5d19683c2ebecfb40e125The uncultured microbial majorityRappe, Michael S.; Giovannoni, Stephen J.Annual Review of Microbiology (2003), 57 (), 369-394CODEN: ARMIAZ; ISSN:0066-4227. (Annual Reviews Inc.)A review. Since the delineation of 12 bacterial phyla by comparative phylogenetic analyses of 16S rRNA in 1987, knowledge of microbial diversity has expanded dramatically owing to the sequencing of rRNA genes cloned from environmental DNA. Currently, only 26 of the approx. 52 identifiable major lineages, or phyla, within the domain Bacteria have cultivated representatives. Evidence from field studies indicates that many of the uncultivated phyla are found in diverse habitats, and some are extraordinarily abundant. In some important environments, including seawater, freshwater, and soil, many biol. and geochem. important organisms are at best only remotely related to any strain that has been characterized by phenotype or by genome sequencing. Genome sequence information that would allow rRNA gene trees to be related to broader patterns in microbial genome evolution is scant, and therefore microbial diversity remains largely unexplored territory.
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105Geerlings, S. Y.; Ouwerkerk, J. P.; Koehorst, J. J.; Ritari, J.; Aalvink, S.; Stecher, B.; Schaap, P. J.; Paulin, L.; de Vos, W. M.; Belzer, C. Genomic convergence between Akkermansia muciniphila in different mammalian hosts. BMC Microbiol. 2021, 21, 298, DOI: 10.1186/s12866-021-02360-6Google Scholar105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVeiur%252FJ&md5=fc1edb781f16cb7d3e74f2063be471a8Genomic convergence between Akkermansia muciniphila in different mammalian hostsGeerlings, Sharon Y.; Ouwerkerk, Janneke P.; Koehorst, Jasper J.; Ritari, Jarmo; Aalvink, Steven; Stecher, Baerbel; Schaap, Peter J.; Paulin, Lars; de Vos, Willem M.; Belzer, ClaraBMC Microbiology (2021), 21 (1), 298CODEN: BMMIBC; ISSN:1471-2180. (BioMed Central Ltd.)Akkermansia muciniphila is a member of the human gut microbiota where it resides in the mucus layer and uses mucin as the sole carbon, nitrogen and energy source. A. muciniphila is the only representative of the Verrucomicrobia phylum in the human gut. However, A. muciniphila 16S rRNA gene sequences have also been found in the intestines of many vertebrates. We detected A. muciniphila-like bacteria in the intestines of animals belonging to 15 out of 16 mammalian orders. In addn., other species belonging to the Verrucomicrobia phylum were detected in fecal samples. We isolated 10 new A. muciniphila strains from the feces of chimpanzee, siamang, mouse, pig, reindeer, horse and elephant. The physiol. and genome of these strains were highly similar in comparison to the type strain A. muciniphila MucT. Overall, the genomes of the new strains showed high av. nucleotide identity (93.9 to 99.7%). In these genomes, we detected considerable conservation of at least 75 of the 78 mucin degrdn. genes that were previously detected in the genome of the type strain MucT. The low genomic divergence obsd. in the new strains may indicate that A. muciniphila favors mucosal colonization independent of the differences in hosts. In addn., the conserved mucus degrdn. capability points towards a similar beneficial role of the new strains in regulating host metabolic health.
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106Liu, M.-J.; Yang, J.-Y.; Yan, Z.-H.; Hu, S.; Li, J.-Q.; Xu, Z.-X.; Jian, Y.-P. Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases. Clin. Nutr. 2022, 41, 2333– 2344, DOI: 10.1016/j.clnu.2022.08.029Google Scholar106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFCqur3N&md5=8427cc10cfe52ddeada931c698ff2bf9Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseasesLiu, Meng-Jie; Yang, Jing-Yu; Yan, Zhen-Hua; Hu, Shuang; Li, Jun-Qi; Xu, Zhi-Xiang; Jian, Yong-PingClinical Nutrition (2022), 41 (10), 2333-2344CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)A review. The mammalian gastrointestinal tract is colonized with a majority of gut microbes, affecting host metab. and homeostasis. Gut microbiota plays a vital role in nutrient exchange, signaling transduction between intestinal epithelial cells, and resistance to pathogen invasion. Gut microbiota is divided into mucus layer bacteria and intestinal lumen bacteria based on the colonization distribution. Akkermansia muciniphila (A. muciniphila) prefers to colonize in the intestinal mucus layer, and specifically degrades mucins to produce short-chain fatty acids, providing energy for the host and promoting colonization of the bacterium itself. Degrdn. of mucins prompts the host to compensate for the prodn. of more mucins, thereby maintaining the dynamics of these proteins. In the intestinal micro-ecosystem, A. muciniphila is non-pathogenic, and its colonization with suitable abundance contributes to the development of immune system, thus promoting intestinal health. The mechanisms by which A. muciniphila bears a protective role in the host intestine are currently unclear. We summarize the microenvironment for the colonization of A. muciniphila, physiol. characteristics and pathophysiol. impact of A. muciniphila on intestinal diseases, such as irritable bowel syndrome, inflammatory bowel diseases, and intestinal tumors. We also provided updates for current studies on signals that A. muciniphila enhances intestinal barrier integrity and regulates immune response. Together, we conclude that A. muciniphila is a promising probiotic, which could be a microbial target for the treatment of multiple intestinal diseases.
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107Gupta, R. S.; Sethi, M. Phylogeny and molecular signatures for the phylum Fusobacteria and its distinct subclades. Anaerobe 2014, 28, 182– 198, DOI: 10.1016/j.anaerobe.2014.06.007Google Scholar107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlCltLvM&md5=e31bb61fa4c7b945081a26c98b3d8573Phylogeny and molecular signatures for the phylum Fusobacteria and its distinct subcladesGupta, Radhey S.; Sethi, MohitAnaerobe (2014), 28 (), 182-198CODEN: ANAEF8; ISSN:1075-9964. (Elsevier Ltd.)The members of the phylum Fusobacteria and its two families, Fusobacteriaceae and Leptotrichiaceae, are distinguished at present mainly on the basis of their branching in the 16S rRNA gene trees and anal. of the internal transcribed spacer sequences in the 16S-23S rDNA. However, no biochem. or mol. characteristics are known that are uniquely shared by all of most members of these groups of bacteria. We report here detailed phylogenetic and comparative analyses on 45 sequenced Fusobacteria genomes to examine their evolutionary relationships and to identify mol. markers that are specific for the members of this phylum. In phylogenetic trees based on 16S rRNA gene sequences or concatenated sequences for 17 conserved proteins, members of the families Fusobacteriaceae and Leptotrichiaceae formed strongly supported clades and were clearly distinguished. In these trees, the species from the genus Fusobacterium also formed a no. of well-supported clades. In parallel, comparative analyses on Fusobacteria genomes have identified 44 conserved signature indels (CSIs) in proteins involved in a broad range of functions that are either specific for the phylum Fusobacteria or a no. of distinct subclades within this phylum. Seven of these CSIs in important proteins are uniquely present in the protein homologs of all sequenced Fusobacteria and they provide potential mol. markers for this phylum. Six and three other CSIs in other protein sequences are specific for members of the families Fusobacteriaceae and Leptotrichiaceae, resp., and they provide novel mol. means for distinguishing members of these two families. Fourteen addnl. CSIs in different proteins, which are specific for either members of the genera Fusobacterium or Leptotrichia, or a no. of other well-supported clades of Fusobacteria at multiple phylogenetic levels, provide mol. markers for these groups and information regarding the evolutionary relationships among the members of this phylum. Lastly, the present work has also identified 14 CSIs in divergent proteins that are specific for three specific subclades of Fusobacterium species, which are also indicated to be distinct by phylogenetic analyses. The members of these three Fusobacterium subclades also differ significantly from each other in their whole genome av. nucleotide identities values, suggesting that they are possible candidates for recognition as different genera. The mol. markers reported here provide novel means for the identification of members of the phylum Fusobacteria and for their classification.
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108Madhogaria, B.; Bhowmik, P.; Kundu, A. Correlation between human gut microbiome and diseases. Infectious Medicine 2022, 1, 180– 191, DOI: 10.1016/j.imj.2022.08.004Google ScholarThere is no corresponding record for this reference.
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109Bull, M. J.; Plummer, N. T. Part 1: The Human Gut Microbiome in Health and Disease. Integr. Med. 2014, 13, 17– 22Google Scholar109https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28ngslCqtg%253D%253D&md5=1e800609aae342509788de2879a22170Part 1: The Human Gut Microbiome in Health and DiseaseBull Matthew J; Plummer Nigel TIntegrative medicine (Encinitas, Calif.) (2014), 13 (6), 17-22 ISSN:1546-993X.The bacterial cells harbored within the human gastrointestinal tract (GIT) outnumber the host's cells by a factor of 10 and the genes encoded by the bacteria resident within the GIT outnumber their host's genes by more than 100 times. These human digestive-tract associated microbes are referred to as the gut microbiome. The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physiology, and immune function. Imbalance of the normal gut microbiota have been linked with gastrointestinal conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and wider systemic manifestations of disease such as obesity, type 2 diabetes, and atopy. In the first part of this review, we evaluate our evolving knowledge of the development, complexity, and functionality of the healthy gut microbiota, and the ways in which the microbial community is perturbed in dysbiotic disease states; the second part of this review covers the role of interventions that have been shown to modulate and stabilize the gut microbiota and also to restore it to its healthy composition from the dysbiotic states seen in IBS, IBD, obesity, type 2 diabetes, and atopy.
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110Vijay, A.; Valdes, A. M. Role of the gut microbiome in chronic diseases: a narrative review. Eur. J. Clin. Nutr. 2022, 76, 489– 501, DOI: 10.1038/s41430-021-00991-6Google Scholar110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjsVOntbc%253D&md5=df621b3f9e2bfd638c58c1209db0de71Role of the gut microbiome in chronic diseases: a narrative reviewVijay, Amrita; Valdes, Ana M.European Journal of Clinical Nutrition (2022), 76 (4), 489-501CODEN: EJCNEQ; ISSN:0954-3007. (Nature Portfolio)A review. The gut microbiome, i.e., the community of bacteria and other microorganisms living in the human gut, has been implicated both directly and indirectly (mediating the effects of diet) on human health. The assocns. between gut microbiome compn. and disease status have been widely reported, while recent studies have demonstrated a role for the gut microbiome in influencing remote organs, mucosal, and immune function. This review details the role of the gut microbiome in chronic diseases and ways it can be modulated for the management or prevention of chronic conditions. The aim of this narrative review is to describe the assocns. between gut microbiome compn. and various types of chronic diseases and to discuss the links to habitual diet and dietary components. Discussed here is the gut microbiome compn. and its assocn. with autoimmune diseases, gut inflammation/bowel disorders, cardiometabolic diseases, chronic kidney disease (CKD). Finally, the gut microbiome is studied as a therapeutic target in the treatment of chronic diseases.
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111Baquero, F.; Nombela, C. The microbiome as a human organ. Clin Microbiol Infect 2012, 18 (Suppl 4), 2– 4, DOI: 10.1111/j.1469-0691.2012.03916.xGoogle Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFOrsr7J&md5=83369e0cc4a735dd21ea26982b23bd9eThe microbiome as a human organBaquero, F.; Nombela, C.Clinical Microbiology and Infection (2012), 18 (Suppl. 4), 2-4CODEN: CMINFM; ISSN:1198-743X. (Wiley-Blackwell)A review. The human organism is a complex structure composed of cells belonging to all three domains of life on Earth, Eukarya, Bacteria and Archaea, as well as their viruses. Bacterial cells of more than a thousand taxonomic units are condensed in a particular functional collective domain, the intestinal microbiome. The microbiome constitutes the last human organ under active research. Like other organs, and despite its intrinsic complexity, the microbiome is readily inherited, in a process probably involving 'small world' power law dynamics of construction in newborns. Like any other organ, the microbiome has physiol. and pathol., and the individual (and collective) health might be damaged when its collective population structure is altered. The diagnostic of microbiomic diseases involves metagenomic studies. The therapeutics of microbiome-induced pathol. include microbiota transplantation, a technique increasingly available. Perhaps a new medical specialty, microbiomol., is being born.
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112Evans, J. M.; Morris, L. S.; Marchesi, J. R. The gut microbiome: the role of a virtual organ in the endocrinology of the host. J. Endocrinol. 2013, 218, R37– R47, DOI: 10.1530/JOE-13-0131Google Scholar112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1WltLjF&md5=3ab2a34ea51b8140d352b87e480f1b0aThe gut microbiome: the role of a virtual organ in the endocrinology of the hostEvans, James M.; Morris, Laura S.; Marchesi, Julian R.Journal of Endocrinology (2013), 218 (3), R37-R47CODEN: JOENAK; ISSN:0022-0795. (BioScientifica Ltd.)A review. The human microbiome contains a vast array of microbes and genes that show greater complexity than the host's own karyome; the functions of many of these microbes are beneficial and show co-evolution with the host, while others are detrimental. The microbiota that colonises the gut is now being considered as a virtual organ or emergent system, with properties that need to be integrated into host biol. and physiol. Unlike other organs, the functions that the gut microbiota plays in the host are as yet not fully understood and can be quite easily disrupted by antibiotics, diet or surgery. In this review, we look at some of the best-characterised functions that only the gut microbiota plays and how it interacts with the host's endocrine system and we try to make it clear that the 21st-century biol. cannot afford to ignore this facet of biol., if it wants to fully understand what makes us human.
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113Haseeb, A.; Shahzad, I.; Ghulam, H.; Muhammad Naeem, F.; Humaira, M.; Imtiaz, M.; Imran, M.; Saima, M.; Muhammad Irfan, U. Gut Microbiome: A New Organ System in Body. In Parasitology and Microbiology Research; Gilberto Antonio Bastidas, P., Asghar Ali, K., Eds.; IntechOpen: Rijeka, Croatia, 2019.Google ScholarThere is no corresponding record for this reference.
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114Cani, P. D. Human gut microbiome: hopes, threats and promises. Gut 2018, 67, 1716– 1725, DOI: 10.1136/gutjnl-2018-316723Google Scholar114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVehtLc%253D&md5=c4f47f74d81d89dee22cc32b466a3f11Human gut microbiome: hopes, threats and promisesCani, Patrice D.Gut (2018), 67 (9), 1716-1725CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)A review. The microbiome has received increasing attention over the last 15 years. Although gut microbes have been explored for several decades, investigations of the role of microorganisms that reside in the human gut has attracted much attention beyond classical infectious diseases. For example, numerous studies have reported changes in the gut microbiota during not only obesity, diabetes, and liver diseases but also cancer and even neurodegenerative diseases. The human gut microbiota is viewed as a potential source of novel therapeutics. Between 2013 and 2017, the no. of publications focusing on the gut microbiota was, remarkably, 12 900, which represents four-fifths of the total no. of publications over the last 40 years that investigated this topic. This review discusses recent evidence of the impact of the gut microbiota on metabolic disorders and focus on selected key mechanisms. This review also aims to provide a crit. anal. of the current knowledge in this field, identify putative key issues or problems and discuss misinterpretations. The abundance of metagenomic data generated on comparing diseased and healthy subjects can lead to the erroneous claim that a bacterium is causally linked with the protection or the onset of a disease. In fact, environmental factors such as dietary habits, drug treatments, intestinal motility and stool frequency and consistency are all factors that influence the compn. of the microbiota and should be considered. The cases of the bacteria Prevotella copri and Akkermansia muciniphila will be discussed as key examples.
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115Lloyd-Price, J.; Arze, C.; Ananthakrishnan, A. N.; Schirmer, M.; Avila-Pacheco, J.; Poon, T. W.; Andrews, E.; Ajami, N. J.; Bonham, K. S.; Brislawn, C. J. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 2019, 569, 655– 662, DOI: 10.1038/s41586-019-1237-9Google Scholar115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVOgtL3O&md5=4376c66207c176377e5b973777fba13bMulti-omics of the gut microbial ecosystem in inflammatory bowel diseasesLloyd-Price, Jason; Arze, Cesar; Ananthakrishnan, Ashwin N.; Schirmer, Melanie; Avila-Pacheco, Julian; Poon, Tiffany W.; Andrews, Elizabeth; Ajami, Nadim J.; Bonham, Kevin S.; Brislawn, Colin J.; Casero, David; Courtney, Holly; Gonzalez, Antonio; Graeber, Thomas G.; Hall, A. Brantley; Lake, Kathleen; Landers, Carol J.; Mallick, Himel; Plichta, Damian R.; Prasad, Mahadev; Rahnavard, Gholamali; Sauk, Jenny; Shungin, Dmitry; Vazquez-Baeza, Yoshiki; White, Richard A., III; Braun, Jonathan; Denson, Lee A.; Jansson, Janet K.; Knight, Rob; Kugathasan, Subra; McGovern, Dermot P. B.; Petrosino, Joseph F.; Stappenbeck, Thaddeus S.; Winter, Harland S.; Clish, Clary B.; Franzosa, Eric A.; Vlamakis, Hera; Xavier, Ramnik J.; Huttenhower, CurtisNature (London, United Kingdom) (2019), 569 (7758), 655-662CODEN: NATUAS; ISSN:0028-0836. (Nature Research)Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clin., immunol., mol., genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal mol. profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as mol. disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochem. shifts. Finally, integrative anal. identified microbial, biochem., and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
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116Mars, R. A. T.; Yang, Y.; Ward, T.; Houtti, M.; Priya, S.; Lekatz, H. R.; Tang, X.; Sun, Z.; Kalari, K. R.; Korem, T. Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome. Cell 2020, 182, 1460– 1473.e17, DOI: 10.1016/j.cell.2020.08.007Google Scholar116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVajsL3M&md5=75eaf2c7114cfb7251564c30c6687b75Longitudinal multi-omics reveals Subset-Specific Mechanisms Underlying Irritable Bowel SyndromeMars, Ruben A. T.; Yang, Yi; Ward, Tonya; Houtti, Mo; Priya, Sambhawa; Lekatz, Heather R.; Tang, Xiaojia; Sun, Zhifu; Kalari, Krishna R.; Korem, Tal; Bhattarai, Yogesh; Zheng, Tenghao; Bar, Noam; Frost, Gary; Johnson, Abigail J.; van Treuren, Will; Han, Shuo; Ordog, Tamas; Grover, Madhusudan; Sonnenburg, Justin; D'Amato, Mauro; Camilleri, Michael; Elinav, Eran; Segal, Eran; Blekhman, Ran; Farrugia, Gianrico; Swann, Jonathan R.; Knights, Dan; Kashyap, Purna C.Cell (Cambridge, MA, United States) (2020), 182 (6), 1460-1473.e17CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Detg. its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiol. changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiol. We identified IBS subtype-specific and symptom-related variation in microbial compn. and function. A subset of identified changes in microbial metabolites correspond to host physiol. mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metab. as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.
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117Rinttilä, T.; Lyra, A.; Krogius-Kurikka, L.; Palva, A. Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjects. Gut Pathog. 2011, 3, 6, DOI: 10.1186/1757-4749-3-6Google Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsl2ntb0%253D&md5=4f84e5c6102f7ffaea8fb030757f88c3Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjectsRinttila, Teemu; Lyra, Anna; Krogius-Kurikka, Lotta; Palva, AiriGut Pathogens (2011), 3 (), 6CODEN: GPUAB2; ISSN:1757-4749. (BioMed Central Ltd.)Growing amt. of scientific evidence suggests that microbes are involved in the pathophysiol. of irritable bowel syndrome (IBS). The predominant fecal microbiota compn. of IBS subjects has been widely studied with DNA-based techniques but less research has been focused on the intestinal pathogens in this disorder. Here, we optimized a highly sensitive panel of 12 quant. real-time PCR (qPCR) assays to shed light on the putative presence of intestinal pathogens in IBS sufferers. The panel was used to screen fecal samples from 96 IBS subjects and 23 healthy controls. Fifteen IBS samples (17%) tested pos. for Staphylococcus aureus with a thermonuclease (nuc) gene-targeting qPCR assay, whereas none of the healthy controls were pos. for S. aureus (p < 0.05). The S. aureus-pos. IBS samples were confirmed by sequencing of the PCR amplicons. Clostridium perfringens was detected from IBS and control groups with a similar frequency (13% and 17%, resp.) with α-toxin (plc) gene-targeting qPCR assay while none of the samples tested pos. for the Cl. perfringens enterotoxin-encoding gene (cpe). The qPCR panel consisting of 12 assays for an extensive set of pathogenic microorganisms provides an efficient alternative to the conventional detection of gastrointestinal pathogens and could accelerate the initiation of targeted antibiotic therapy reducing the risk of post-infectious IBS (PI-IBS). S. aureus has not been previously reported to be assocd. with the onset of IBS. Although we discovered significant differences in the prevalence of S. aureus between the study groups, its importance in giving rise to IBS symptoms requires further studies.
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118Mayer, E. A.; Nance, K.; Chen, S. The Gut-Brain Axis. Annu. Rev. Med. 2022, 73, 439– 453, DOI: 10.1146/annurev-med-042320-014032Google Scholar118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cjit1ejsA%253D%253D&md5=e416e85301b2698d90fce325d3075f21The Gut-Brain AxisMayer Emeran A; Nance Karina; Chen ShelleyAnnual review of medicine (2022), 73 (), 439-453 ISSN:.Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Alterations in gut-brain-microbiome interactions have been identified in rodent models of several digestive, psychiatric, and neurological disorders. While alterations in gut-brain interactions have clearly been established in irritable bowel syndrome, a causative role of the microbiome in irritable bowel syndrome remains to be determined. In the absence of specific microbial targets for more effective therapies, current approaches are limited to dietary interventions and centrally targeted pharmacological and behavioral approaches. A more comprehensive understanding of causative influences within the gut-brain-microbiome system and well-designed randomized controlled trials are needed to translate these exciting preclinical findings into effective therapies.
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119Zhang, T.; Zhang, C.; Zhang, J.; Sun, F.; Duan, L. Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis. Front Cell Infect Microbiol 2022, 12, 859967, DOI: 10.3389/fcimb.2022.859967Google Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MvosVOnsQ%253D%253D&md5=435ad6a1bd9f95fbed238df0e858e8d9Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-AnalysisZhang Tao; Zhang Cunzheng; Zhang Jindong; Duan Liping; Sun Feng; Sun FengFrontiers in cellular and infection microbiology (2022), 12 (), 859967 ISSN:.Background: Irritable bowel syndrome (IBS) is a common gastrointestinal condition. Studies regarding the treatment of IBS with probiotics have not yielded consistent results, and the best probiotics has not yet been confirmed. Therefore, we performed a network meta-analysis (NMA) to assess the relative rank order of different probiotics for IBS. Method: We searched for RCTs on the efficacy of probiotics for IBS until August 25, 2021. The primary outcome was the symptom relief rate, as well as global symptoms, abdominal pain, bloating, and straining scores. The NMA was conducted using Stata 15.0. We also used meta-regression to explore whether the treatment length and dose influenced the efficacy. Results: Forty-three RCTs, with 5,531 IBS patients, were included in this analysis. Firstly, we compared the efficacy of different probiotic species. B.coagulans exhibited the highest probability to be the optimal probiotic specie in improving IBS symptom relief rate, as well as global symptom, abdominal pain, bloating, and straining scores. In regard to the secondary outcomes, L.plantarum ranked first in ameliorating the QOL of IBS patients, but without any significant differences compared with other probiotic species in standardized mean differences (SMD) estimates. Moreover, patients received L.acidophilus had lowest incidence of adverse events. The meta-regression revealed that no significant differences were found between participants using different doses of probiotics in all outcomes, while the treatment length, as a confounder, can significantly influence the efficacy of probiotics in ameliorating abdominal pain (Coef = -2.30; p = 0.035) and straining (Coef = -3.15; p = 0.020) in IBS patients. Thus, we performed the subgroup analysis on treatment length subsequently in these two outcomes, which showed that efficacy of B.coagulans using 8 weeks ranked first both in improving the abdominal pain and straining scores. Additionally, B. coagulans still had significant efficacy compared to different types of probiotic combinations in present study. Conclusions: The findings of this NMA suggested that B.coagulans had prominent efficacy in treating IBS patients, and incorporating B.coagulans into a probiotic combination, or genetically engineering it to amplify its biological function may be a future research target to treat IBS patients. With few direct comparisons available between individual therapies today, this NMA may have utility in forming treatment guideline for IBS with probiotics.
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120Ponnusamy, K.; Choi, J. N.; Kim, J.; Lee, S. Y.; Lee, C. H. Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J. Med. Microbiol. 2011, 60, 817– 827, DOI: 10.1099/jmm.0.028126-0Google Scholar120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXotlyktL8%253D&md5=45cb3406def633eeb56142c42ee8112bMicrobial community and metabolomic comparison of irritable bowel syndrome faecesPonnusamy, Kannan; Choi, Jung Nam; Kim, Jiyoung; Lee, Sun-Young; Lee, Choong HwanJournal of Medical Microbiology (2011), 60 (6), 817-827CODEN: JMMIAV; ISSN:0022-2615. (Society for General Microbiology)Human health relies on the compn. of microbiota in an individual's gut and the synthesized metabolites that may alter the gut environment. Gut microbiota and fecal metabolites are involved in several gastrointestinal diseases. In this study, 16S rRNA-specific denaturing gradient gel electrophoresis and quant. PCR anal. showed that the mean similarity of total bacteria was significantly different (P<0.001) in fecal samples from patients with irritable bowel syndrome (IBS; n=11) and from non-IBS (nIBS) patients (n=8). IBS subjects had a significantly higher diversity of total bacteria, as measured by the Shannon index (H') (3.36<H'<4.37, P=0.004), Bacteroidetes and lactobacilli; however, less diversity was obsd. for Bifidobacter (1.7< H'<3.08, P<0.05) and Clostridium coccoides (0.9< H'<2.98, P=0.007). In this study, no significant difference was found in total bacterial quantity (P>0.05). GC/MS-based multi-variate anal. delineated the fecal metabolites of IBS from nIBS samples. Elevated levels of amino acids (alanine and pyroglutamic acid) and phenolic compds. (hydroxyphenyl acetate and hydroxyphenyl propionate) were found in IBS. These results were highly correlated with the abundance of lactobacilli and Clostridium, which indicates an altered metab. rate assocd. with these gut microorganisms. A higher diversity of Bacteroidetes and Lactobacillus groups in IBS fecal samples also correlated with the resp. total quantity. In addn., these changes altered protein and carbohydrate energy metab. in the gut.
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121Rajilić-Stojanović, M.; Biagi, E.; Heilig, H. G.; Kajander, K.; Kekkonen, R. A.; Tims, S.; de Vos, W. M. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011, 141, 1792– 1801, DOI: 10.1053/j.gastro.2011.07.043Google Scholar121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlOksbrN&md5=da9f508d81243c976bedbd98e3d369ecGlobal and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel SyndromeRajilic-Stojanovic, Mirjana; Biagi, Elena; Heilig, Hans G. H. J.; Kajander, Kajsa; Kekkonen, Riina A.; Tims, Sebastian; de Vos, Willem M.Gastroenterology (2011), 141 (5), 1792-1801CODEN: GASTAB; ISSN:0016-5085. (Elsevier)Background & Aims: Irritable bowel syndrome (IBS) has been assocd. with disruptions to the intestinal microbiota, but studies have had limited power, coverage, and depth of anal. We aimed to define microbial populations that can be used discriminate the fecal microbiota of patients with IBS from that of healthy subjects and correlate these with IBS intestinal symptom scores. Methods: The microbiota compn. was assessed by global and deep mol. anal. of fecal samples from 62 patients with IBS patients and 46 healthy individuals (controls). We used a comprehensive and highly reproducible phylogenetic microarray in combination with quant. polymerase chain reaction. Results: The intestinal microbiota of IBS patients differed significantly (P = .0005) from that of controls. The microbiota of patients, compared with controls, had a 2-fold increased ratio of the Firmicutes to Bacteroidetes (P = .0002). This resulted from an approx. 1.5-fold increase in nos. of Dorea, Ruminococcus, and Clostridium spp (P < .005); a 2-fold decrease in the no. of Bacteroidetes (P < .0001); a 1.5-fold decrease in nos. of Bifidobacterium and Faecalibacterium spp (P < .05); and, when present, a 4-fold lower av. no. of methanogens (3.50 × 107 vs 8.74 × 106 cells/g feces; P = .003). Correlation anal. of the microbial groups and IBS symptom scores indicated the involvement of several groups of Firmicutes and Proteobacteria in the pathogenesis of IBS. Conclusions: Global and deep mol. anal. of fecal samples indicates that patients with IBS have a different compn. of microbiota. This information might be used to develop better diagnostics and ultimately treatments for IBS.
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122Pittayanon, R.; Lau, J. T.; Yuan, Y.; Leontiadis, G. I.; Tse, F.; Surette, M.; Moayyedi, P. Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. Gastroenterology 2019, 157, 97– 108, DOI: 10.1053/j.gastro.2019.03.049Google Scholar122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M%252FhtVaisg%253D%253D&md5=9c44fc6126c5738a4923952192240d91Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic ReviewPittayanon Rapat; Lau Jennifer T; Yuan Yuhong; Leontiadis Grigorios I; Tse Frances; Surette Michael; Moayyedi PaulGastroenterology (2019), 157 (1), 97-108 ISSN:.BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is common but difficult to treat. Altering the gut microbiota has been proposed as a strategy for treatment of IBS, but the association between the gut microbiome and IBS symptoms has not been well established. We performed a systematic review to explore evidence for this association. METHODS: We searched databases, including MEDLINE, EMBASE, Cochrane CDSR, and CENTRAL, through April 2, 2018 for case-control studies comparing the fecal or colon microbiomes of adult or pediatric patients with IBS with microbiomes of healthy individuals (controls). The primary outcome was differences in specific gut microbes between patients with IBS and controls. RESULTS: The search identified 2631 citations; 24 studies from 22 articles were included. Most studies evaluated adults presenting with various IBS subtypes. Family Enterobacteriaceae (phylum Proteobacteria), family Lactobacillaceae, and genus Bacteroides were increased in patients with IBS compared with controls, whereas uncultured Clostridiales I, genus Faecalibacterium (including Faecalibacterium prausnitzii), and genus Bifidobacterium were decreased in patients with IBS. The diversity of the microbiota was either decreased or not different in IBS patients compared with controls. More than 40% of included studies did not state whether cases and controls were comparable (did not describe sex and/or age characteristics). CONCLUSIONS: In a systematic review, we identified specific bacteria associated with microbiomes of patients with IBS vs controls. Studies are needed to determine whether these microbes are a product or cause of IBS.
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123El-Salhy, M.; Hatlebakk, J. G.; Gilja, O. H.; Bråthen Kristoffersen, A.; Hausken, T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut 2020, 69, 859– 867, DOI: 10.1136/gutjnl-2019-319630Google Scholar123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVCht7vI&md5=5ff6c2ba597e8af3db30ac4569f6c021Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled studyEl-Salhy, Magdy; Hatlebakk, Jan Gunnar; Gilja, Odd Helge; Kristoffersen, Anja Braathen; Hausken, TrygveGut (2020), 69 (5), 859-867CODEN: GUTTAK; ISSN:0017-5749. (BMJ)Objective Faecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings. Design This randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a redn. in the IBS symptoms at 3 mo after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a redn. in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analyzed by 16S rRNA gene sequencing, at 1 mo following FMT. Results Responses occurred in 23.6%, 76.9% (p < 0.0001) and 89.1% (p < 00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, resp. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms. Conclusions FMT is an effective treatment for patients with IBS. Utilizing a well-defined donor with a normal DI and favorable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose.
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124Wilson, B.; Rossi, M.; Kanno, T.; Parkes, G. C.; Anderson, S.; Mason, A. J.; Irving, P. M.; Lomer, M. C.; Whelan, K. β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal Bifidobacteria. Am. J. Gastroenterol. 2020, 115, 906– 915, DOI: 10.14309/ajg.0000000000000641Google Scholar124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38vpsVGgsA%253D%253D&md5=aa2615e105539ac6d3a069d39e76b492β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal BifidobacteriaWilson Bridgette; Rossi Megan; Lomer Miranda C; Whelan Kevin; Wilson Bridgette; Lomer Miranda C; Kanno Tokuwa; Mason A James; Parkes Gareth C; Anderson Simon; Irving Peter MThe American journal of gastroenterology (2020), 115 (6), 906-915 ISSN:.INTRODUCTION: The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. METHODS: We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. RESULTS: At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). DISCUSSION: The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.
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125Vasant, D. H.; Paine, P. A.; Black, C. J.; Houghton, L. A.; Everitt, H. A.; Corsetti, M.; Agrawal, A.; Aziz, I.; Farmer, A. D.; Eugenicos, M. P. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021, 70, 1214– 1240, DOI: 10.1136/gutjnl-2021-324598Google Scholar125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sblvVektg%253D%253D&md5=3d4f2e18c2008dea28e43666bd713126British Society of Gastroenterology guidelines on the management of irritable bowel syndromeVasant Dipesh H; Vasant Dipesh H; Paine Peter A; Paine Peter A; Black Christopher J; Ford Alexander C; Black Christopher J; Houghton Lesley A; Ford Alexander C; Houghton Lesley A; Everitt Hazel A; Corsetti Maura; Agrawal Anurag; Aziz Imran; Aziz Imran; Farmer Adam D; Farmer Adam D; Eugenicos Maria P; Moss-Morris Rona; Yiannakou YanGut (2021), 70 (7), 1214-1240 ISSN:.Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.
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126Moayyedi, P.; Andrews, C. N.; MacQueen, G.; Korownyk, C.; Marsiglio, M.; Graff, L.; Kvern, B.; Lazarescu, A.; Liu, L.; Paterson, W. G. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS). J. Can. Assoc Gastroenterol 2019, 2, 6– 29, DOI: 10.1093/jcag/gwy071Google Scholar126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mzmt1OnsA%253D%253D&md5=0774e7ab2ec3948ad8c141e21c61867aCanadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS)Moayyedi Paul; Sidani Sacha; Andrews Christopher N; MacQueen Glenda; Korownyk Christina; Marsiglio Megan; Graff Lesley; Kvern Brent; Lazarescu Adriana; Liu Louis; Paterson William G; Vanner StephenJournal of the Canadian Association of Gastroenterology (2019), 2 (1), 6-29 ISSN:.BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS. METHODS: A systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient. RESULTS: Consensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments. CONCLUSIONS: Patients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.
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127Fukudo, S.; Okumura, T.; Inamori, M.; Okuyama, Y.; Kanazawa, M.; Kamiya, T.; Sato, K.; Shiotani, A.; Naito, Y.; Fujikawa, Y. Evidence-based clinical practice guidelines for irritable bowel syndrome 2020. J. Gastroenterol. 2021, 56, 193– 217, DOI: 10.1007/s00535-020-01746-zGoogle Scholar127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srpsFajtg%253D%253D&md5=1e7734581ce8e2ac14b0c96312d3c01aEvidence-based clinical practice guidelines for irritable bowel syndrome 2020Fukudo Shin; Okumura Toshikatsu; Inamori Masahiko; Okuyama Yusuke; Kanazawa Motoyori; Kamiya Takeshi; Sato Ken; Shiotani Akiko; Naito Yuji; Fujikawa Yoshiko; Hokari Ryota; Masaoka Tastuhiro; Fujimoto Kazuma; Kaneko Hiroshi; Torii Akira; Matsueda Kei; Miwa Hiroto; Enomoto Nobuyuki; Shimosegawa Tooru; Koike Kazuhiko; Fukudo ShinJournal of gastroenterology (2021), 56 (3), 193-217 ISSN:.Managing irritable bowel syndrome (IBS) has attracted international attention because single-agent therapy rarely relieves bothersome symptoms for all patients. The Japanese Society of Gastroenterology (JSGE) published the first edition of evidence-based clinical practice guidelines for IBS in 2015. Much more evidence has accumulated since then, and new pharmacological agents and non-pharmacological methods have been developed. Here, we report the second edition of the JSGE-IBS guidelines comprising 41 questions including 12 background questions on epidemiology, pathophysiology, and diagnostic criteria, 26 clinical questions on diagnosis and treatment, and 3 questions on future research. For each question, statements with or without recommendations and/or evidence level are given and updated diagnostic and therapeutic algorithms are provided based on new evidence. Algorithms for diagnosis are requisite for patients with chronic abdominal pain or associated symptoms and/or abnormal bowel movement. Colonoscopy is indicated for patients with one or more alarm symptoms/signs, risk factors, and/or abnormal routine examination results. The diagnosis is based on the Rome IV criteria. Step 1 therapy consists of diet therapy, behavioral modification, and gut-targeted pharmacotherapy for 4 weeks. For non-responders, management proceeds to step 2 therapy, which includes a combination of different mechanistic gut-targeted agents and/or psychopharmacological agents and basic psychotherapy for 4 weeks. Step 3 therapy is for non-responders to step 2 and comprises a combination of gut-targeted pharmacotherapy, psychopharmacological treatments, and/or specific psychotherapy. These updated JSGE-IBS guidelines present best practice strategies for IBS patients in Japan and we believe these core strategies can be useful for IBS diagnosis and treatment globally.
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128Lacy, B. E.; Pimentel, M.; Brenner, D. M.; Chey, W. D.; Keefer, L. A.; Long, M. D.; Moshiree, B. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am. J. Gastroenterol. 2021, 116, 17, DOI: 10.14309/ajg.0000000000001036Google Scholar128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXnt1Grtrk%253D&md5=26264e26c18a80d33974d3dbdddf4303ACG clinical guideline: management of irritable bowel syndromeLacy, Brian E.; Pimentel, Mark; Brenner, Darren M.; Chey, William D.; Keefer, Laurie A.; Long, Millie D.; Moshiree, BahaAmerican Journal of Gastroenterology (2021), 116 (1), 17-44CODEN: AJGAAR; ISSN:1572-0241. (Wolters Kluwer)Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterol. clin. guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodol. Twenty-five clin. important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodol., we endorse the following: We suggest that a pos. diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serol. testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Addnl. statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.
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129Ford, A. C.; Harris, L. A.; Lacy, B. E.; Quigley, E. M. M.; Moayyedi, P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment. Pharmacol. Ther. 2018, 48, 1044– 1060, DOI: 10.1111/apt.15001Google Scholar129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3czmslWmuw%253D%253D&md5=f74e29349f47d2004d956c06846f4691Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndromeFord Alexander C; Ford Alexander C; Harris Lucinda A; Lacy Brian E; Quigley Eamonn M M; Moayyedi PaulAlimentary pharmacology & therapeutics (2018), 48 (10), 1044-1060 ISSN:.BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology. AIM: To perform a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials (RCTs) recruiting adults with IBS, comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardised mean difference with a 95% CI. RESULTS: The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty-three RCTs of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non-constipated IBS patients, which was more effective than placebo (RR of symptoms persisting = 0.84; 95% CI 0.79-0.90). Adverse events were no more common with probiotics or antibiotics. CONCLUSIONS: Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non-constipated IBS.
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130Caruso, R.; Lo, B. C.; Núñez, G. Host-microbiota interactions in inflammatory bowel disease. Nat. Rev. Immunol. 2020, 20, 411– 426, DOI: 10.1038/s41577-019-0268-7Google Scholar130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXislequ70%253D&md5=3ebd4c5a2950e065f9c578324d0643b5Host-microbiota interactions in inflammatory bowel diseaseCaruso, Roberta; Lo, Bernard C.; Nunez, GabrielNature Reviews Immunology (2020), 20 (7), 411-426CODEN: NRIABX; ISSN:1474-1733. (Nature Research)Abstr.: The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. The presence of large nos. of symbionts near the epithelial surface of the intestine poses an enormous challenge to the host because it must avoid the activation of harmful inflammatory responses to the microorganisms while preserving its ability to mount robust immune responses to invading pathogens. In patients with inflammatory bowel disease, there is a breakdown of the multiple strategies that the immune system has evolved to promote the sepn. between symbiotic microorganisms and the intestinal epithelium and the effective killing of penetrant microorganisms, while suppressing the activation of inappropriate T cell responses to resident microorganisms. Understanding the complex interactions between intestinal microorganisms and the host may provide crucial insight into the pathogenesis of inflammatory bowel disease as well as new avenues to prevent and treat the disease.
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131Federici, S.; Kredo-Russo, S.; Valdés-Mas, R.; Kviatcovsky, D.; Weinstock, E.; Matiuhin, Y.; Silberberg, Y.; Atarashi, K.; Furuichi, M.; Oka, A. Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. Cell 2022, 185, 2879– 2898.e24, DOI: 10.1016/j.cell.2022.07.003Google Scholar131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitVChurfF&md5=e0fa16b8aea85b8df9c03a9e7ca246d8Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammationFederici, Sara; Kredo-Russo, Sharon; Valdes-Mas, Rafael; Kviatcovsky, Denise; Weinstock, Eyal; Matiuhin, Yulia; Silberberg, Yael; Atarashi, Koji; Furuichi, Munehiro; Oka, Akihiko; Liu, Bo; Fibelman, Morine; Weiner, Iddo Nadav; Khabra, Efrat; Cullin, Nyssa; Ben-Yishai, Noa; Inbar, Dana; Ben-David, Hava; Nicenboim, Julian; Kowalsman, Noga; Lieb, Wolfgang; Kario, Edith; Cohen, Tal; Geffen, Yael Friedman; Zelcbuch, Lior; Cohen, Ariel; Rappo, Urania; Gahali-Sass, Inbar; Golembo, Myriam; Lev, Vered; Dori-Bachash, Mally; Shapiro, Hagit; Moresi, Claudia; Cuevas-Sierra, Amanda; Mohapatra, Gayatree; Kern, Lara; Zheng, Danping; Nobs, Samuel Philip; Suez, Jotham; Stettner, Noa; Harmelin, Alon; Zak, Naomi; Puttagunta, Sailaja; Bassan, Merav; Honda, Kenya; Sokol, Harry; Bang, Corinna; Franke, Andre; Schramm, Christoph; Maharshak, Nitsan; Sartor, Ryan Balfour; Sorek, Rotem; Elinav, EranCell (Cambridge, MA, United States) (2022), 185 (16), 2879-2898.e24CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geog. distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly assocd. with disease exacerbation and severity. Transfer of clin. IBD-assocd. Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-assocd. Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.
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132Nagalingam, N. A.; Lynch, S. V. Role of the microbiota in inflammatory bowel diseases. Inflamm. Bowel Dis. 2012, 18, 968– 984, DOI: 10.1002/ibd.21866Google Scholar132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38zlvFehuw%253D%253D&md5=36eaa38f264de538590085654a704292Role of the microbiota in inflammatory bowel diseasesNagalingam Nabeetha A; Lynch Susan VInflammatory bowel diseases (2012), 18 (5), 968-84 ISSN:.Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field.
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133Barcenilla, A.; Pryde, S. E.; Martin, J. C.; Duncan, S. H.; Stewart, C. S.; Henderson, C.; Flint, H. J. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 2000, 66, 1654– 1661, DOI: 10.1128/AEM.66.4.1654-1661.2000Google Scholar133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXisVWmu7g%253D&md5=98a4294d41eb8141fdda17b857791129Phylogenetic relationships of butyrate-producing bacteria from the human gutBarcenilla, Adela; Pryde, Susan E.; Martin, Jennifer C.; Duncan, Sylvia H.; Stewart, Colin S.; Henderson, Colin; Flint, Harry J.Applied and Environmental Microbiology (2000), 66 (4), 1654-1661CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)Butyrate is a preferred energy source for colonic epithelial cells and is thought to play an important role in maintaining colonic health in humans. In order to investigate the diversity and stability of butyrate-producing organisms of the colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly voided human fecal samples from 3 healthy individuals: an infant, an adult omnivore, and an adult vegetarian. A 2nd isolation was performed on the same 3 individuals 1 yr later. Of a total of 313 bacterial isolates, 74 produced more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism anal. The results indicate very little overlap between the predominant ribotypes of the 3 subjects; furthermore, the flora of each individual changed significantly between the 2 isolations. Complete sequences of 16S rDNAs were detd. for 24 representative strains and subjected to phylogenetic anal. Eighty percent of the butyrate-producing isolates fell within the XIVa cluster of gram-pos. bacteria as defined by M. D. Collins et al. and A. Willems et al., with the most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale, Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the butyrate-producing isolates were net acetate consumers during growth, suggesting that they employ the butyryl CoA-acetyl CoA transferase pathway for butyrate prodn. In contrast, only 1% of the 239 non-butyrate-producing isolates consumed acetate.
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134Halfvarson, J.; Brislawn, C. J.; Lamendella, R.; Vázquez-Baeza, Y.; Walters, W. A.; Bramer, L. M.; D’Amato, M.; Bonfiglio, F.; McDonald, D.; Gonzalez, A. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat. Microbiol 2017, 2, 17004, DOI: 10.1038/nmicrobiol.2017.4Google Scholar134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkvFyqt7s%253D&md5=31d20fb740e9e065969614896c2cca3aDynamics of the human gut microbiome in inflammatory bowel diseaseHalfvarson, Jonas; Brislawn, Colin J.; Lamendella, Regina; Vazquez-Baeza, Yoshiki; Walters, William A.; Bramer, Lisa M.; D'Amato, Mauro; Bonfiglio, Ferdinando; McDonald, Daniel; Gonzalez, Antonio; McClure, Erin E.; Dunklebarger, Mitchell F.; Knight, Rob; Jansson, Janet K.Nature Microbiology (2017), 2 (1), 17004CODEN: NMAICH; ISSN:2058-5276. (Nature Publishing Group)Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The etiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behavior of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, esp. subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between obsd. dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.
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135Mottawea, W.; Chiang, C.-K.; Mühlbauer, M.; Starr, A. E.; Butcher, J.; Abujamel, T.; Deeke, S. A.; Brandel, A.; Zhou, H.; Shokralla, S. Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease. Nat. Commun. 2016, 7, 13419, DOI: 10.1038/ncomms13419Google Scholar135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitFSns77P&md5=700643e7cd70e13bb35625e955a3bce7Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's diseaseMottawea, Walid; Chiang, Cheng-Kang; Muhlbauer, Marcus; Starr, Amanda E.; Butcher, James; Abujamel, Turki; Deeke, Shelley A.; Brandel, Annette; Zhou, Hu; Shokralla, Shadi; Hajibabaei, Mehrdad; Singleton, Ruth; Benchimol, Eric I.; Jobin, Christian; Mack, David R.; Figeys, Daniel; Stintzi, AlainNature Communications (2016), 7 (), 13419CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Intestinal microbial dysbiosis is assocd. with Crohn's disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation anal. reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host-microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.
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136Marchesi, J. R.; Holmes, E.; Khan, F.; Kochhar, S.; Scanlan, P.; Shanahan, F.; Wilson, I. D.; Wang, Y. Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J. Proteome Res. 2007, 6, 546– 551, DOI: 10.1021/pr060470dGoogle Scholar136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhs12gtQ%253D%253D&md5=af033580ca436e4056e7262110730ac1Rapid and Noninvasive Metabonomic Characterization of Inflammatory Bowel DiseaseMarchesi, Julian R.; Holmes, Elaine; Khan, Fatima; Kochhar, Sunil; Scanlan, Pauline; Shanahan, Fergus; Wilson, Ian D.; Wang, YulanJournal of Proteome Research (2007), 6 (2), 546-551CODEN: JPROBS; ISSN:1535-3893. (American Chemical Society)Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have a major impact on the health of individuals and populations. Accurate diagnosis of inflammatory bowel disease (IBD) at an early stage, and correct differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is important for optimum treatment and prognosis. The authors present here the first characterization of fecal exts. obtained from patients with CD and UC by employing a noninvasive metabonomics approach, which combines high resoln. 1H NMR spectroscopy and multivariate pattern recognition techniques. The fecal exts. of both CD and UC patients were characterized by reduced levels of butyrate, acetate, methylamine, and trimethylamine in comparison with a control population, suggesting changes in the gut microbial community. Also, elevated quantities of amino acids were present in the feces from both disease groups, implying malabsorption caused by the inflammatory disease or an element of protein losing enteropathy. Metabolic differences in fecal profiles were more marked in the CD group in comparison with the control group, indicating that the inflammation caused by CD is more extensive in comparison with UC and involves the whole intestine. Furthermore, glycerol resonances were a dominant feature of fecal spectra from patients with CD but were present in much lower intensity in the control and UC groups. This work illustrates the potential of metabonomics to generate novel noninvasive diagnostics for gastrointestinal diseases and may further our understanding of disease mechanisms.
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137Van Immerseel, F.; Ducatelle, R.; De Vos, M.; Boon, N.; Van De Wiele, T.; Verbeke, K.; Rutgeerts, P.; Sas, B.; Louis, P.; Flint, H. J. Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease. J. Med. Microbiol. 2010, 59, 141– 143, DOI: 10.1099/jmm.0.017541-0Google Scholar137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c%252FktVGltQ%253D%253D&md5=c0e88381cc635630a1a3d0362ffeb7c2Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel diseaseVan Immerseel Filip; Ducatelle Richard; De Vos Martine; Boon Nico; Van De Wiele Tom; Verbeke Kristin; Rutgeerts Paul; Sas Benedikt; Louis Petra; Flint Harry JJournal of medical microbiology (2010), 59 (Pt 2), 141-143 ISSN:.There is no expanded citation for this reference.
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138Miquel, S.; Martín, R.; Rossi, O.; Bermúdez-Humarán, L. G.; Chatel, J. M.; Sokol, H.; Thomas, M.; Wells, J. M.; Langella, P. Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol. 2013, 16, 255– 261, DOI: 10.1016/j.mib.2013.06.003Google Scholar138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKqsr7K&md5=9d63ee3ca46ee654075ae06da77ef52fFaecalibacterium prausnitzii and human intestinal healthMiquel, S.; Martin, R.; Rossi, O.; Bermudez-Humaran, L. G.; Chatel, J. M.; Sokol, H.; Thomas, M.; Wells, J. M.; Langella, P.Current Opinion in Microbiology (2013), 16 (3), 255-261CODEN: COMIF7; ISSN:1369-5274. (Elsevier Ltd.)A review. Faecalibacterium prausnitzii is the most abundant bacterium in the human intestinal microbiota of healthy adults, representing more than 5% of the total bacterial population. Over the past five years, an increasing no. of studies have clearly described the importance of this highly metabolically active commensal bacterium as a component of the healthy human microbiota. Changes in the abundance of F. prausnitzii have been linked to dysbiosis in several human disorders. Administration of F. prausnitzii strain A2-165 and its culture supernatant have been shown to protect against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Here, we discuss the role of F. prausnitzii in balancing immunity in the intestine and the mechanisms involved.
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139Tamanai-Shacoori, Z.; Smida, I.; Bousarghin, L.; Loreal, O.; Meuric, V.; Fong, S. B.; Bonnaure-Mallet, M.; Jolivet-Gougeon, A. Roseburia spp.: a marker of health?. Future Microbiol. 2017, 12, 157– 170, DOI: 10.2217/fmb-2016-0130Google Scholar139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslWhtbY%253D&md5=9d57c7df0d1668e2bb44e05afd2e45edRoseburia spp.: a marker of health?Tamanai-Shacoori, Zohreh; Smida, Imen; Bousarghin, Latifa; Loreal, Olivier; Meuric, Vincent; Fong, Shao Bing; Bonnaure-Mallet, Martine; Jolivet-Gougeon, AnneFuture Microbiology (2017), 12 (2), 157-170CODEN: FMUIAR; ISSN:1746-0913. (Future Medicine Ltd.)A review. The genus Roseburia consists of obligate Gram-pos. anaerobic bacteria that are slightly curved, rod-shaped and motile by means of multiple subterminal flagella. It includes five species: Roseburia intestinalis, R. hominis, R. inulinivorans, R. faecis and R. cecicola. Gut Roseburia spp. metabolize dietary components that stimulate their proliferation and metabolic activities. They are part of commensal bacteria producing short-chain fatty acids, esp. butyrate, affecting colonic motility, immunity maintenance and anti-inflammatory properties. Modification in Roseburia spp. representation may affect various metabolic pathways and is assocd. with several diseases (including irritable bowel syndrome, obesity, Type 2 diabetes, nervous system conditions and allergies). Roseburia spp. could also serve as biomarkers for symptomatic pathologies (e.g., gallstone formation) or as probiotics for restoration of beneficial flora.
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140Li, Y.; Xia, S.; Jiang, X.; Feng, C.; Gong, S.; Ma, J.; Fang, Z.; Yin, J.; Yin, Y. Gut Microbiota and Diarrhea: An Updated Review. Microbiology 2021, 11, 625210, DOI: 10.3389/fcimb.2021.625210Google Scholar140https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sbpt1aluw%253D%253D&md5=efb07829392f2514713f0ede26ef97f8Gut Microbiota and Diarrhea: An Updated ReviewLi Yunxia; Xia Siting; Jiang Xiaohan; Feng Can; Gong Saiming; Ma Jie; Yin Jie; Yin Yulong; Fang Zhengfeng; Yin YulongFrontiers in cellular and infection microbiology (2021), 11 (), 625210 ISSN:.Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.
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141Hodges, K.; Gill, R. Infectious diarrhea: Cellular and molecular mechanisms. Gut Microbes 2010, 1, 4– 21, DOI: 10.4161/gmic.1.1.11036Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sboslOhtA%253D%253D&md5=b0992f6a97ff50dff635deea9065d231Infectious diarrhea: Cellular and molecular mechanismsHodges Kim; Gill RavinderGut microbes (2010), 1 (1), 4-21 ISSN:.Diarrhea caused by enteric infections is a major factor in morbidity and mortality worldwide. An estimated 2-4 billion episodes of infectious diarrhea occur each year and are especially prevalent in infants. This review highlights the cellular and molecular mechanisms underlying diarrhea associated with the three classes of infectious agents, i.e., bacteria, viruses and parasites. Several bacterial pathogens have been chosen as model organisms, including Vibrio cholerae as a classical example of secretory diarrhea, Clostridium difficile and Shigella species as agents of inflammatory diarrhea and selected strains of pathogenic Escherichia coli (E. coli) to discuss the recent advances in alteration of epithelial ion absorption. Many of the recent studies addressing epithelial ion transport and barrier function have been carried out using viruses and parasites. Here, we focus on the rapidly developing field of viral diarrhea including rotavirus, norovirus and astrovirus infections. Finally we discuss Giardia lamblia and Entamoeba histolytica as examples of parasitic diarrhea. Parasites have a greater complexity than the other pathogens and are capable of creating molecules similar to those produced by the host, such as serotonin and PGE(2). The underlying mechanisms of infectious diarrhea discussed include alterations in ion transport and tight junctions as well as the virulence factors, which alter these processes either through direct effects or indirectly through inflammation and neurotransmitters.
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142Levine, M. M. Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J. Infect. Dis. 1987, 155, 377– 389, DOI: 10.1093/infdis/155.3.377Google Scholar142https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL2s7htVylsw%253D%253D&md5=28f3bb6db9138f13a131fadf174fe710Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherentLevine M MThe Journal of infectious diseases (1987), 155 (3), 377-89 ISSN:0022-1899.There are four major categories of diarrheagenic Escherichia coli: enterotoxigenic (a major cause of travelers' diarrhea and infant diarrhea in less-developed countries), enteroinvasive (a cause of dysentery), enteropathogenic (an important cause of infant diarrhea), and enterohemorrhagic (a cause of hemorrhagic colitis and hemolytic uremic syndrome). Besides manifesting distinct clinical patterns, these categories of E. coli differ in their epidemiology and pathogenesis and in their O:H serotypes. Common features (albeit distinct for each category) include plasmid-encoded virulence properties, characteristic interactions with intestinal mucosa, and elaboration of various types of enterotoxins or cytotoxins. A less-well-defined fifth category of diarrheagenic E. coli is that of enteroadherent E. coli, so far identifiable only by their pattern of adherence to Hep-2 cells in tissue culture.
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143Gallo, A.; Passaro, G.; Gasbarrini, A.; Landolfi, R.; Montalto, M. Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate. World J. Gastroenterol. 2016, 22, 7186– 7202, DOI: 10.3748/wjg.v22.i32.7186Google Scholar143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2svgtVCqtw%253D%253D&md5=976dc72a198f8a598627eb8a347d3c7cModulation of microbiota as treatment for intestinal inflammatory disorders: An uptodateGallo Antonella; Passaro Giovanna; Gasbarrini Antonio; Landolfi Raffaele; Montalto MassimoWorld journal of gastroenterology (2016), 22 (32), 7186-202 ISSN:.Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.
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144Bron, P. A.; Kleerebezem, M.; Brummer, R. J.; Cani, P. D.; Mercenier, A.; MacDonald, T. T.; Garcia-Ródenas, C. L.; Wells, J. M. Can probiotics modulate human disease by impacting intestinal barrier function?. Br. J. Nutr. 2017, 117, 93– 107, DOI: 10.1017/S0007114516004037Google Scholar144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvVyks74%253D&md5=73dd9acb7e2cf433fbcfb1a3d706d8e5Can probiotics modulate human disease by impacting intestinal barrier function?Bron, Peter A.; Kleerebezem, Michiel; Brummer, Robert-Jan; Cani, Patrice D.; Mercenier, Annick; MacDonald, Thomas T.; Garcia-Rodenas, Clara L.; Wells, Jerry M.British Journal of Nutrition (2017), 117 (1), 93-107CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chem. and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major etiol. factors assocd. with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in which in vitro cell lines, animal models and clin. trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the redn. of gastrointestinal disease symptoms.
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145Zhang, S.; Wang, R.; Li, D.; Zhao, L.; Zhu, L. Role of gut microbiota in functional constipation. Gastroenterol. Rep. 2021, 9, 392– 401, DOI: 10.1093/gastro/goab035Google Scholar145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cjos1eitw%253D%253D&md5=d9df2a9e9bd37ff2920138061a0d473eRole of gut microbiota in functional constipationZhang Shengsheng; Wang Ruixin; Li Danyan; Zhao Luqing; Zhu LixinGastroenterology report (2021), 9 (5), 392-401 ISSN:2052-0034.Functional constipation (FC) is common, yet the etiology is not clear. Accumulating evidence suggests an association between FC and abnormal gut microbiota. The relationship between the gut microbiota and the gut transit is likely bidirectional. This review summarizes the current evidence regarding the impact of gut microbiota on the pathogenesis of FC. By modulating the colonic motility, secretion, and absorption, gut microbiota may contribute to the development of FC through microbial metabolic activities involving bile acids, short-chain fatty acids, 5-hydroxytryptamine, and methane. In support of the key roles of the gut microbiota in FC, treatment with probiotics, prebiotics, synbiotics, and traditional Chinese medicine often result in compositional and functional changes in the gut microbiota. Further studies on the pathogenesis of FC and the therapeutic mechanism of microecological agents will provide a knowledge base for better management of FC.
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146Zoppi, G.; Cinquetti, M.; Luciano, A.; Benini, A.; Muner, A.; Bertazzoni Minelli, E. The intestinal ecosystem in chronic functional constipation. Acta Paediatr. 1998, 87, 836– 841, DOI: 10.1111/j.1651-2227.1998.tb01547.xGoogle Scholar146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1cvgsFKgtQ%253D%253D&md5=bb92c7610207657d2e9c5dad125d53c2The intestinal ecosystem in chronic functional constipationZoppi G; Cinquetti M; Luciano A; Benini A; Muner A; Bertazzoni Minelli EActa paediatrica (Oslo, Norway : 1992) (1998), 87 (8), 836-41 ISSN:0803-5253.Chronic functional constipation is common in infants, and the bacterial composition of stools in this condition is not known. The study aims were to: (i) investigate the composition of the intestinal ecosystem in chronic functional constipation; (ii) establish whether the addition of the water-holding agent calcium polycarbophil to the diet induces an improvement in constipation; and (iii) determine the composition of the intestinal ecosystem after the use of this agent. In total, 42 children (20F, 22M; mean age: 8.6 +/- 2.9 y) were studied. Twenty-eight children with functional chronic constipation without anatomical disorders were treated double-blind in random sequence for 1 month with an oral preparation of calcium polycarbophil (0.62 g/twice daily) or placebo. Intestinal flora composition was evaluated by standard microbiological methods and biochemical assays on faecal samples collected before and after treatment. Fourteen healthy children were studied as controls. The results show that (i) the constipated children presented a significant increase in clostridia and bifidobacteria in faeces compared to healthy subjects--different species of clostridia and enterobacteriaceae were frequently isolated; no generalized overgrowth was observed; Clostridia outnumbered bacteroides and E. coli mean counts by 2-3log, while bacteroides and E. coli counts were similar (5-6 log10/g fresh faeces); these intestinal disturbances could be defined as a dysbiosis, i.e. a quantitative alteration in the relative proportions of certain intestinal bacterial species. (ii) Clinical resolution of constipation was achieved only in 43% of treated children and an improvement in 21% (one bowel movement every 2 d). (iii) Calcium polycarbophil treatment induced no significant changes in the composition of the intestinal ecosystem, nor in blood chemistry parameters.
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147Khalif, I. L.; Quigley, E. M.; Konovitch, E. A.; Maximova, I. D. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig. Liver Dis. 2005, 37, 838– 849, DOI: 10.1016/j.dld.2005.06.008Google Scholar147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MrmsFCntQ%253D%253D&md5=7b2a49da0e98a1645fa10ad657392e4cAlterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipationKhalif I L; Quigley E M M; Konovitch E A; Maximova I DDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2005), 37 (11), 838-49 ISSN:1590-8658.BACKGROUND: Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. AIM: To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. METHODS: Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. RESULTS: Ovalbumin concentrations, in serum, were higher in constipated patients (28.2+/-4.1 ng/ml versus 1.0+/-0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. CONCLUSION: Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation.
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148Kim, S. E.; Choi, S. C.; Park, K. S.; Park, M. I.; Shin, J. E.; Lee, T. H.; Jung, K. W.; Koo, H. S.; Myung, S. J. Change of Fecal Flora and Effectiveness of the Short-term VSL#3 Probiotic Treatment in Patients With Functional Constipation. J. Neurogastroenterol. Motil. 2015, 21, 111– 120, DOI: 10.5056/jnm14048Google Scholar148https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MvhslOltA%253D%253D&md5=bfd9824ac1d168c6ba1dbc0aa8172459Change of Fecal Flora and Effectiveness of the Short-term VSL#3 Probiotic Treatment in Patients With Functional ConstipationKim Seong-Eun; Choi Suck Chei; Park Kyung Sik; Park Moo In; Shin Jeong Eun; Lee Tae Hee; Jung Kee Wook; Myung Seung-Jae; Koo Hoon SupJournal of neurogastroenterology and motility (2015), 21 (1), 111-20 ISSN:2093-0879.BACKGROUND/AIMS: We investigated gut flora characteristics in patients with functional constipation (FC) and influences of short-term treatment with VSL#3 probiotic on flora and symptom improvement. METHODS: Thirty patients fulfilling Rome III criteria for FC and 30 controls were enrolled. Fecal samples were obtained before and after VSL#3 intake (one sachet twice daily for 2 weeks) and flora were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Symptom changes were also investigated. RESULTS: The fold differences in Bifidobacterium and Bacteroides species were significantly lower in feces from FC, compared to in controls (P = 0.030 and P = 0.021). After taking VSL#3, the fold differences in Lactobacillus, Bifidobacterium and Bacteroides species increased in controls (P = 0.022, P = 0.018, and P = 0.076), but not in FC. Mean Bristol scores and complete spontaneous bowel movements (CSBMs)/week increased significantly in FC after ingesting VSL#3 (both P < 0.001). Relief of subjective CSBM frequency, stool consistency and abdominal bloating were reported in 70%, 60%, and 47% of patients. After VSL#3 cessation, 44.4% of patients with symptom improvement experienced constipation recurrence mostly within one month. CONCLUSIONS: Bifidobacterium and Bacteroides species might be quantitatively altered in FC. A short-term VSL#3 treatment can improve clinical symptoms of FC. Further studies are needed to investigate VSL#3's additional effects beyond altering gut flora to allevate constipation.
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149Zhu, L.; Liu, W.; Alkhouri, R.; Baker, R. D.; Bard, J. E.; Quigley, E. M.; Baker, S. S. Structural changes in the gut microbiome of constipated patients. Physiol. Genomics 2014, 46, 679– 686, DOI: 10.1152/physiolgenomics.00082.2014Google Scholar149https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGqu7%252FO&md5=8b1c0286b36bab313ee6443b9d83bde3Structural changes in the gut microbiome of constipated patientsZhu, Lixin; Liu, Wensheng; Alkhouri, Razan; Baker, Robert D.; Bard, Jonathan E.; Quigley, Eamonn M.; Baker, Susan S.Physiological Genomics (2014), 46 (18), 679-686CODEN: PHGEFP; ISSN:1094-8341. (American Physiological Society)Previous studies using culture-based methods suggested an assocn. between constipation and altered abundance of certain taxa of the colonic microbiome. We aim to examine the global changes in gut microbial compn. of constipated patients. A cross-sectional pilot study using 16S rRNA gene pyrosequencing was performed to compare stool microbial compn. of eight constipated patients and 14 nonconstipated controls. Only obese children were enrolled so that the microbiome features assocd. with constipation would not be obscured by those assocd. with obesity. The sequencing reads were processed by QIIME for quant. anal. of the microbial compn. at genus and above levels. Dietary intake for all the individuals was assessed by dietary recalls and a food frequency questionnaire. The ecol. diversities of fecal microbiome of the constipated patients differed from those of the controls. Significantly decreased abundance in Prevotella and increased representation in several genera of Firmicutes were obsd. in constipated patients compared with controls. The conventional probiotic genera Lactobacillus and Bifidobacteria were not decreased in the microbiomes of the constipated patients. These alterations in the fecal microbiome of constipated patients suggested that a novel probiotic treatment including certain Prevotella strains may be more effective than conventional probiotic products incorporating Lactobacillus or Bifidobacterium species. While it is possible that the obsd. changes in the microbiome in constipated subjects are a consequence of a low-fiber diet, these changes also predict a different pattern of bacterial fermn. end-products, such as increased butyrate prodn., which may contribute to pathogenesis of constipation.
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150Mancabelli, L.; Milani, C.; Lugli, G. A.; Turroni, F.; Mangifesta, M.; Viappiani, A.; Ticinesi, A.; Nouvenne, A.; Meschi, T.; van Sinderen, D. Unveiling the gut microbiota composition and functionality associated with constipation through metagenomic analyses. Sci. Rep. 2017, 7, 9879, DOI: 10.1038/s41598-017-10663-wGoogle Scholar150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cbislGnsw%253D%253D&md5=1285e7fb794c5d616cac6450d7923cbeUnveiling the gut microbiota composition and functionality associated with constipation through metagenomic analysesMancabelli Leonardo; Milani Christian; Lugli Gabriele Andrea; Turroni Francesca; Mangifesta Marta; Ventura Marco; Mangifesta Marta; Viappiani Alice; Ticinesi Andrea; Nouvenne Antonio; Meschi Tiziana; van Sinderen DouweScientific reports (2017), 7 (1), 9879 ISSN:.Functional constipation (FC) is a gastrointestinal disorder with a high prevalence among the general population. The precise causes of FC are still unknown and are most likely multifactorial. Growing evidence indicates that alterations of gut microbiota composition contribute to constipation symptoms. Nevertheless, many discrepancies exist in literature and no clear link between FC and gut microbiota composition has as yet been identified. In this study, we performed 16 S rRNA-based microbial profiling analysis of 147 stool samples from 68 FC individuals and compared their microbial profiles with those of 79 healthy subjects (HS). Notably, the gut microbiota of FC individuals was shown to be depleted of members belonging to Bacteroides, Roseburia and Coprococcus 3. Furthermore, the metabolic capabilities of the gut microbiomes of five FC and five HS individuals were evaluated through shotgun metagenomics using a MiSeq platform, indicating that HS are enriched in pathways involved in carbohydrate, fatty acid and lipid metabolism as compared to FC. In contrast, the microbiomes corresponding to FC were shown to exhibit high abundance of genes involved in hydrogen production, methanogenesis and glycerol degradation. The identified differences in bacterial composition and metabolic capabilities may play an important role in development of FC symptoms.
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151Naseer, M.; Poola, S.; Uraz, S.; Tahan, V. Therapeutic Effects of Prebiotics on Constipation: A Schematic Review. Curr. Clin. Pharmacol. 2020, 15, 207– 215, DOI: 10.2174/1574884715666200212125035Google Scholar151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB387ht1ShsA%253D%253D&md5=333bbe352c02460c64cc165b31ad482bTherapeutic Effects of Prebiotics on Constipation: A Schematic ReviewNaseer Maliha; Poola Shiva; Uraz Suleyman; Tahan VeyselCurrent clinical pharmacology (2020), 15 (3), 207-215 ISSN:.Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics to play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested, stimulating the bacteria. There are a variety of prebiotics; however, there exists only a handful of studies that describe their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfil the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation were used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear.
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152Zhao, Y.; Yu, Y. B. Intestinal microbiota and chronic constipation. SpringerPlus 2016, 5, 1130, DOI: 10.1186/s40064-016-2821-1Google Scholar152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3msFOgsA%253D%253D&md5=c5af5044bf440bc6084a4e44e7fb775bIntestinal microbiota and chronic constipationZhao Ying; Yu Yan-BoSpringerPlus (2016), 5 (1), 1130 ISSN:2193-1801.Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose aetiology and pathophysiology remains poorly understood and is most likely multifactorial. Differences in the composition of the intestinal microbiota have been demonstrated when constipated patients and healthy controls have been compared. Growing evidence indicates that alterations of intestinal microbiota may contribute to constipation and constipation-related symptoms. The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, and perform many important health-promoting functions. The intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, prevents growth of pathogenic bacteria and produces a great variety of biologically important compounds. In this review, we will summarize the current evidence supporting roles of the intestinal microbiota in the pathogenesis and management of chronic constipation. The discussion will shed light on the novel mechanisms of intestinal microbiota and gut function interactions, which is invaluable in ultimately developing new therapeutic tools for the treatment of chronic constipation.
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153Wang, J. K.; Yao, S. K. Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation. Evid. Based Complement. Alternat. Med. 2021, 2021, 5560310, DOI: 10.1155/2021/5560310Google Scholar153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cnls1Khtg%253D%253D&md5=e92d8375b6e14e6d3f100cd1a98f292dRoles of Gut Microbiota and Metabolites in Pathogenesis of Functional ConstipationWang Jun-Ke; Yao Shu-KunEvidence-based complementary and alternative medicine : eCAM (2021), 2021 (), 5560310 ISSN:1741-427X.Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.
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154Rao, S. S.; Rattanakovit, K.; Patcharatrakul, T. Diagnosis and management of chronic constipation in adults. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 295– 305, DOI: 10.1038/nrgastro.2016.53Google Scholar154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XlvVahsLk%253D&md5=91b31cc77cb456a5854799580e9fbb52Diagnosis and management of chronic constipation in adultsRao, Satish S. C.; Rattanakovit, Kulthep; Patcharatrakul, TanisaNature Reviews Gastroenterology & Hepatology (2016), 13 (5), 295-305CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary constipation can result from drug treatment, neurol. or metabolic conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation is made after exclusion of secondary causes of constipation and encompasses several overlapping subtypes. Slow-transit constipation is characterized by prolonged colonic transit in the absence of pelvic floor dysfunction. This subtype of constipation can be identified using either the radio-opaque marker test or wireless motility capsule test, and is best treated with laxatives such as polyethylene glycol or newer agents such as linaclotide or lubiprostone. If unsuccessful, subspecialist referral should be considered. Dyssynergic defecation results from impaired coordination of rectoanal and pelvic floor muscles, and causes difficulty with defecation. The condition can be identified using anorectal manometry and balloon expulsion tests and is best managed with biofeedback therapy. Opioid-induced constipation is an emerging entity, and several drugs including naloxegol, methylnaltrexone and lubiprostone are approved for its treatment. In this Review, we provide an overview of the burden and pathophysiol. of chronic constipation, as well as a detailed discussion of the available diagnostic tools and treatment options.
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155Moloney, R. D.; Desbonnet, L.; Clarke, G.; Dinan, T. G.; Cryan, J. F. The microbiome: stress, health and disease. Mamm. Genome 2014, 25, 49– 74, DOI: 10.1007/s00335-013-9488-5Google Scholar155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXisVCjurs%253D&md5=9a35ad22dd20c688980e752910dab5f5The microbiome: stress, health and diseaseMoloney, Rachel D.; Desbonnet, Lieve; Clarke, Gerard; Dinan, Timothy G.; Cryan, John F.Mammalian Genome (2014), 25 (1-2), 49-74CODEN: MAMGEC; ISSN:0938-8990. (Springer)A review. Bacterial colonization of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathol. of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome-brain-gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.
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156Mayer, E. A.; Tillisch, K.; Gupta, A. Gut/brain axis and the microbiota. J. Clin. Invest. 2015, 125, 926– 938, DOI: 10.1172/JCI76304Google Scholar156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MrmtFamsw%253D%253D&md5=5d580088b116af24ebfcd56dc65685c1Gut/brain axis and the microbiotaMayer Emeran A; Tillisch Kirsten; Gupta ArpanaThe Journal of clinical investigation (2015), 125 (3), 926-38 ISSN:.Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gut microbiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gut microbiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gut microbiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease.
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157Maldonado-Contreras, A.; Noel, S. E.; Ward, D. V.; Velez, M.; Mangano, K. M. Associations between Diet, the Gut Microbiome, and Short-Chain Fatty Acid Production among Older Caribbean Latino Adults. J. Acad. Nutr. Diet. 2020, 120, 2047– 2060.e46, DOI: 10.1016/j.jand.2020.04.018Google Scholar157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38flslGluw%253D%253D&md5=9bc2c76ab72b39cc1244e29a64cae3caAssociations between Diet, the Gut Microbiome, and Short-Chain Fatty Acid Production among Older Caribbean Latino AdultsMaldonado-Contreras Ana; Noel Sabrina E; Ward Doyle V; Velez Martha; Mangano Kelsey MJournal of the Academy of Nutrition and Dietetics (2020), 120 (12), 2047-2060.e6 ISSN:2212-2672.BACKGROUND: Caribbean Latino adults have disproportionately high prevalence of chronic disease; however, underlying mechanisms are unknown. Unique gut microbiome profiles and relation to dietary quality may underlie health disparities. OBJECTIVES: To examine the dietary quality of an underrepresented group of Caribbean Latino older adults with high prevalence of chronic disease; characterize gut microbiome profiles in this cohort; determine associations between dietary quality, gut microbiome composition, and short-chain fatty acid (SCFA) production; examine associations of clinical factors (body mass index, type 2 diabetes [T2D] status, and laxative use) with gut microbiome composition. DESIGN: The study design was cross-sectional. PARTICIPANTS/SETTING: Recruitment and interviews occurred at the Senior Center in Lawrence, MA, from September 2016-September 2017. A total of 20 adults aged ≥50 years, self-identified of Caribbean Latino origin, without use of antibiotics in 6 months or intestinal surgery were included in the study. EXPOSURE AND OUTCOME MEASURES: Diet was assessed by two, 24-hour recalls and dietary quality was calculated using the Healthy Eating Index 2015 and the Mediterranean Diet Score. The gut microbiome was assessed by 16S rRNA sequencing and fecal SCFA content. Anthropometrics (ie, weight and height) were measured by a trained interviewer, and self-reported laxative use, and other self-report health outcomes (ie, T2D status) were assessed by questionnaire. STATISTICAL ANALYSES: Faith Phylogenetic Diversity (alpha diversity) and unique fraction metric, or UniFrac (beta diversity) and nonphylogenetic metrics, including Shannon diversity index (alpha diversity) were calculated. Spearman correlations and group comparisons using Kruskal-Wallis test between alpha diversity indexes and nutrient intakes were calculated. Patterns in the microbiome were estimated using a partitioning around medoids with estimation of number of clusters, with optimum average silhouette width. Log odds were calculated to compare predefined nutrients and diet score components between microbiome clusters using multivariable logistic regression, controlling for age and sex. Pearson correlation was used to relate SCFA fecal content to individual nutrients and diet indexes. Final models were additionally adjusted for laxative use. Differences in lifestyle factors by gut microbiome cluster were tested by Fisher's exact test. RESULTS: Generally, there was poor alignment of participant's diets to either the Mediterranean Diet score or Healthy Eating Index 2015. Range in the Healthy Eating Index 2015 was 36 to 90, where only 5% (n=1) of the sample showed high adherence to the Dietary Guidelines for Americans. Mediterranean Diet scores suggested low conformance with a Mediterranean eating pattern (score range=2 to 8, where 45% scored ≤3 [poor adherence]). The gut microbiome separated into two clusters by difference in a single bacterial taxon: Prevotella copri (P copri) (permutational multivariate analysis of variance [PERMANOVA] R(2)=0.576, ADONIS function P=0.001). Significantly lower P copri abundance was observed in cluster 1 compared with cluster 2 (Mann-Whitney P<0.0001). Samples in the P copri dominated cluster 2 showed significantly lower alpha diversity compared with P copri depleted cluster 1 (Shannon diversity index P=0.01). Individuals in the P copri dominated cluster showed a trend toward higher 18:3 α-linolenic fatty acid intakes (P=0.09). Percentage of energy from total fat intake was significantly, positively correlated with fecal acetate (r=0.46; P=0.04), butyrate (r=0.50; P=0.03) and propionate (r=0.52; P=0.02). Associations between dietary intake and composition of the gut microbiome were attenuated by self-report recent laxative use. Individuals with T2D exhibited a significantly greater abundance of the Enterobacteriales (P=0.01) and a trend toward lower fecal content of butyric acid compared to subjects without T2D (P=0.08). Significant beta diversity differences were observed by weight (Mantel P<0.003) and body mass index (Mantel P<0.07). CONCLUSIONS: Two unique microbiome profiles, identified by abundance of P copri, were identified among Caribbean Latino adults. Microbiome profiles and SCFA content were associated with diet, T2D, and lifestyle. Further research is needed to determine the role of P copri and SCFA production in the risk for chronic disease and associated lifestyle predictors.
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158Zhang, H.; Chen, Y.; Wang, Z.; Xie, G.; Liu, M.; Yuan, B.; Chai, H.; Wang, W.; Cheng, P. Implications of Gut Microbiota in Neurodegenerative Diseases. Front. Immunol. 2022, 13, 785644, DOI: 10.3389/fimmu.2022.785644Google Scholar158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtFOkt7fM&md5=68c103031718c0c55e2498bd4b781b40Implications of gut microbiota in neurodegenerative diseasesZhang, Haoming; Chen, Yijia; Wang, Zifan; Xie, Gaijie; Liu, Mingming; Yuan, Boyu; Chai, Hongxia; Wang, Wei; Cheng, PingFrontiers in Immunology (2022), 13 (), 785644CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. The morbidity assocd. with neurodegenerative diseases (NDs) is increasing, posing a threat to the mental and phys. quality of life of humans. The crucial effect of microbiota on brain physiol. processes is mediated through a bidirectional interaction, termed as the gut-brain axis (GBA), which is being investigated in studies. Many clin. and lab. trials have indicated the importance of microbiota in the development of NDs via various microbial mols. that transmit from the gut to the brain across the GBA or nervous system. In this review, we summarize the implications of gut microbiota in ND, which will be beneficial for understanding the etiol. and progression of NDs that may in turn help in developing ND interventions and clin. treatments for these diseases.
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159Roy Sarkar, S.; Banerjee, S. Gut microbiota in neurodegenerative disorders. J. Neuroimmunol. 2019, 328, 98– 104, DOI: 10.1016/j.jneuroim.2019.01.004Google Scholar159https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXht1egsro%253D&md5=cbe8cf0d5ab1219eee5e557cd6340014Gut microbiota in neurodegenerative disordersRoy Sarkar, Suparna; Banerjee, SugatoJournal of Neuroimmunology (2019), 328 (), 98-104CODEN: JNRIDW; ISSN:0165-5728. (Elsevier B.V.)Gut dysbiosis, a primary factor behind various gastrointestinal disorders may also augment lipopolysaccharides, pro-inflammatory cytokines, T helper cells and monocytes causing increased intestinal and BBB permeability via microbiota-gut-brain axis. Consequentially, accumulation of misfolded proteins, axonal damage and neuronal demyelination sets in, thus facilitating the pathogenesis of neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. Studies revealed that intake of probiotics may help in the integrity of intestinal and BBB thus ameliorating the above neurodegenerative disorders. This review summarizes the current understanding of the role of gut microbiota in neurodegenerative disorders and possible intervention strategies.
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160Caspani, G.; Kennedy, S.; Foster, J. A.; Swann, J. Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microbial cell (Graz, Austria) 2019, 6, 454– 481, DOI: 10.15698/mic2019.10.693Google Scholar160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MjhtFWhsA%253D%253D&md5=74a02883592b6c0009887f5ffdb711edGut microbial metabolites in depression: understanding the biochemical mechanismsCaspani Giorgia; Swann Jonathan; Kennedy Sidney; Kennedy Sidney; Kennedy Sidney; Kennedy Sidney; Foster Jane AMicrobial cell (Graz, Austria) (2019), 6 (10), 454-481 ISSN:2311-2638.Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
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161Roubalová, R.; Procházková, P.; Papežová, H.; Smitka, K.; Bilej, M.; Tlaskalová-Hogenová, H. Anorexia nervosa: Gut microbiota-immune-brain interactions. Clin. Nutr. 2020, 39, 676– 684, DOI: 10.1016/j.clnu.2019.03.023Google Scholar161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmtlWltb8%253D&md5=53f56ee5d87562a45c58636f1e4e5c1dAnorexia nervosa: Gut microbiota-immune-brain interactionsRoubalova, Radka; Prochazkova, Petra; Papezova, Hana; Smitka, Kvido; Bilej, Martin; Tlaskalova-Hogenova, HelenaClinical Nutrition (2020), 39 (3), 676-684CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)A review. Anorexia nervosa is a psychiatric disorder defined by an extremely low body wt., a devastating fear of wt. gain, and body image disturbance, however the etiopathogenesis remains unclear. The objective of the article is to provide a comprehensive review on the potential role of gut microbiota in pathogenesis of anorexia nervosa. Recent advances in sequencing techniques used for microbial detection revealed that this disease is assocd. with disruption of the compn. of normal gut microbiota (dysbiosis), manifested by low microbial diversity and taxonomic differences as compared to healthy individuals. Microorganisms present in the gut represent a part of the so called "microbiota-gut-brain" axis that affect the central nervous system and thus human behavior via the prodn. of various neuroactive compds. In addn., cells of the immune system are equipped with receptors for these neuroactive substances. Microbiota of the intestinal system also represent a very important antigenic source. These antigens can mimic some host neuropeptides and neurohormones and thus trigger the prodn. of autoantibodies which cross-react with these compds. The levels and affinities of these antibodies are thought to be assocd. with neuropsychiatric conditions including anxiety, depression, and eating and sleep disorders. The study of microbiota function in diseases could bring new insights to the pathogenetic mechanisms.
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162Zhang, L.; Wang, Y.; Xiayu, X.; Shi, C.; Chen, W.; Song, N.; Fu, X.; Zhou, R.; Xu, Y. F.; Huang, L. Altered Gut Microbiota in a Mouse Model of Alzheimer’s Disease. J. Alzheimers Dis. 2017, 60, 1241– 1257, DOI: 10.3233/JAD-170020Google Scholar162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7htFOnuw%253D%253D&md5=fe7ee394cfc39a0938651c94753ff3f3Altered Gut Microbiota in a Mouse Model of Alzheimer's DiseaseZhang Ling; Wang Ying; Xiayu Xia; Shi Changhua; Chen Wei; Song Nan; Fu Xinjing; Zhou Rui; Xu Yan-Feng; Huang Lan; Zhu Hua; Han Yunlin; Qin Chuan; Zhang Ling; Wang Ying; Xiayu Xia; Shi Changhua; Chen Wei; Song Nan; Fu Xinjing; Zhou Rui; Xu Yan-Feng; Huang Lan; Zhu Hua; Han Yunlin; Qin ChuanJournal of Alzheimer's disease : JAD (2017), 60 (4), 1241-1257 ISSN:.The topic of gut microbiota is currently attracting considerable interest as a potential factor in Alzheimer's disease (AD). However, the extent and time course of alterations in the gut microbiota, and their effects on AD pathology remain uncertain. Herein, we compared the fecal microbiomes and fecal short chain fatty acid composition (SCFAs) between wild-type and AD model mice at different ages under strictly controlled specific pathogen free conditions, and also conducted microscopic investigations of intestinal structures. Our results showed that the microbiota composition and diversity were perturbed and the level of SCFAs was reduced in AD mice, predicting alterations in more than 30 metabolic pathways, which may be associated with amyloid deposition and ultrastructural abnormalities in AD mouse intestine. These findings indicate that AD pathology might not only affect brain function directly, but also exacerbate cognitive deficits through reducing the level of SCFAs via alterations of gut microbiota induced by intestinal amyloid deposition. Our data may support a role of gut microbiota, and suggest a novel route for therapeutic intervention in AD.
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163Wang, L.; Christophersen, C. T.; Sorich, M. J.; Gerber, J. P.; Angley, M. T.; Conlon, M. A. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig. Dis. Sci. 2012, 57, 2096– 2102, DOI: 10.1007/s10620-012-2167-7Google Scholar163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFWhs7fI&md5=70b345cd24f3b076e8a74081fb98afc1Elevated Fecal Short Chain Fatty Acid and Ammonia Concentrations in Children with Autism Spectrum DisorderWang, Lv; Christophersen, Claus Thagaard; Sorich, Michael Joseph; Gerber, Jacobus Petrus; Angley, Manya Therese; Conlon, Michael AllanDigestive Diseases and Sciences (2012), 57 (8), 2096-2102CODEN: DDSCDJ; ISSN:0163-2116. (Springer)Background and Aim: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder where a high frequency of gastrointestinal disturbance (e.g., constipation and diarrhea) is reported. As large bowel fermn. products can have beneficial or detrimental effects on health, these were measured in feces of children with and without ASD to examine whether there is an underlying disturbance in fermn. processes in the disorder. Methods: Fecal samples (48 h) were collected from children with ASD (n = 23), and without ASD (n = 31) of similar age. Concns. of short chain fatty acids, phenols and ammonia were measured. Results: Fecal total short chain fatty acid concns. were significantly higher in children with ASD compared to controls (136.6 ± 8.7 vs. 111.1 ± 6.6 mmol/kg). Moreover, when concns. of fecal acetic, butyric, isobutyric, valeric, isovaleric and caproic acids were measured, all were significantly higher in children with ASD compared with controls except for caproic acid. The concn. of fecal ammonia was also significantly greater in ASD participants than controls (42.7 ± 3.3 vs. 32.3 ± 1.9 mmol/kg). Fecal phenol levels and pH did not differ between groups. Macronutrient intake, as detd. from dietary records kept by caregivers, also did not differ significantly between study groups. Conclusions: Our results suggest fermn. processes or utilization of fermn. products may be altered in children with ASD compared to children without ASD.
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164Galland, L. The gut microbiome and the brain. J. Med. Food 2014, 17, 1261– 1272, DOI: 10.1089/jmf.2014.7000Google Scholar164https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVCisLfF&md5=25f538028791b1083d830713915d4c50The Gut Microbiome and the BrainGalland, LeoJournal of Medicinal Food (2014), 17 (12), 1261-1272CODEN: JMFOFJ; ISSN:1096-620X. (Mary Ann Liebert, Inc.)A review. The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clin. and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurol. manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.
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165Heneka, M. T.; Carson, M. J.; El Khoury, J.; Landreth, G. E.; Brosseron, F.; Feinstein, D. L.; Jacobs, A. H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R. M. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015, 14, 388– 405, DOI: 10.1016/S1474-4422(15)70016-5Google Scholar165https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvVSksrw%253D&md5=df821845eaf19cc6c6a9c6fdf1f805d6Neuroinflammation in Alzheimer's diseaseHeneka, Michael T.; Carson, Monica J.; El Khoury, Joseph; Landreth, Gary E.; Brosseron, Frederic; Feinstein, Douglas L.; Jacobs, Andreas H.; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M.; Herrup, Karl; Frautschy, Sally A.; Finsen, Bente; Brown, Guy C.; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C.; Town, Terrence; Morgan, Dave; Shinohara, Mari L.; Perry, V. Hugh; Holmes, Clive; Bazan, Nicolas G.; Brooks, David J.; Hunot, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.Lancet Neurology (2015), 14 (4), 388-405CODEN: LNAEAM; ISSN:1474-4422. (Elsevier Ltd.)A review. Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunol. mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterized by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide anal. suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunol. processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
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166Ransohoff, R. M. How neuroinflammation contributes to neurodegeneration. Science 2016, 353, 777– 783, DOI: 10.1126/science.aag2590Google Scholar166https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlCju73I&md5=eaa975b2ac5903376d8ac10fed7b0820How neuroinflammation contributes to neurodegenerationRansohoff, Richard M.Science (Washington, DC, United States) (2016), 353 (6301), 777-783CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobar dementia are among the most pressing problems of developed societies with aging populations. Neurons carry out essential functions such as signal transmission and network integration in the central nervous system and are the main targets of neurodegenerative disease. In this Review, I address how the neuron's environment also contributes to neurodegeneration. Maintaining an optimal milieu for neuronal function rests with supportive cells termed glia and the blood-brain barrier. Accumulating evidence suggests that neurodegeneration occurs in part because the environment is affected during disease in a cascade of processes collectively termed neuroinflammation. These observations indicate that therapies targeting glial cells might provide benefit for those afflicted by neurodegenerative disorders.
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167Karlsson, O.; Roman, E.; Berg, A. L.; Brittebo, E. B. Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period. Behav. Brain Res. 2011, 219, 310– 320, DOI: 10.1016/j.bbr.2011.01.056Google Scholar167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjs1yrtrw%253D&md5=e396db542acd6ea46235a8af414949ecEarly hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal periodKarlsson, Oskar; Roman, Erika; Berg, Anna-Lena; Brittebo, Eva B.Behavioural Brain Research (2011), 219 (2), 310-320CODEN: BBREDI; ISSN:0166-4328. (Elsevier B.V.)We have reported previously that exposure to the cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) during the neonatal period causes cognitive impairments in adult rats. The aim of this study was to investigate the long-term effects of neonatal BMAA exposure on learning and memory mechanisms and to identify early morphol. changes in the neonatal brain. BMAA was injected s.c. in rat pups on postnatal days 9-10. BMAA (50 and 200 mg/kg) caused distinct deficits in spatial learning and memory in adult animals but no morphol. changes. No impairment of recognition memory was detected, suggesting that neonatal exposure to BMAA preferentially affects neuronal systems that are important for spatial tasks. Histopathol. examn. revealed early neuronal cell death as detd. by TUNEL staining in the hippocampus 24 h after a high dose (600 mg/kg) of BMAA whereas no changes were obsd. at lower doses (50 and 200 mg/kg). In addn., there was a low degree of neuronal cell death in the retrosplenial and cingulate cortices, areas that are also important for cognitive function. Taken together, these results indicate that BMAA is a developmental neurotoxin inducing long-term changes in cognitive function. The risk posed by BMAA as a potential human neurotoxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed.
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168Nunes-Costa, D.; Magalhães, J. D.; G-Fernandes, M.; Cardoso, S. M.; Empadinhas, N. Microbial BMAA and the Pathway for Parkinson’s Disease Neurodegeneration. Front. Aging Neurosci. 2020, 12, 26, DOI: 10.3389/fnagi.2020.00026Google Scholar168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1OlsrnP&md5=2430730210ba86f0235baecc1bc46bedMicrobial BMAA and the pathway for Parkinson's disease neurodegenerationNunes-Costa, Daniela; Magalhaes, Joao Duarte; G-Fernandes, Maria; Cardoso, Sandra Morais; Empadinhas, NunoFrontiers in Aging Neuroscience (2020), 12 (), 26CODEN: FANRC5; ISSN:1663-4365. (Frontiers Media S.A.)The neurotoxin β-N-methylamino-L-alanine (BMAA) is a natural non-proteinogenic diamino acid produced by several species of both prokaryotic (cyanobacteria) and eukaryotic (diatoms and dinoflagellates) microorganisms. BMAA has been shown to biomagnify through the food chain in some ecosystems, accumulating for example in seafood such as shellfish and fish, common dietary sources of BMAA whose ingestion may have possible neuronal consequences. In addn. to its excitotoxic potential, BMAA has been implicated in protein misfolding and aggregation, inhibition of specific enzymes and neuroinflammation, all hallmark features of neurodegenerative diseases. However, the exact mol. mechanisms of neurotoxicity remain to be elucidated in detail. Although BMAA is commonly detected in its free form, complex BMAA-contg. mols. have also been identified such as the paenilamicins, produced by an insect gut bacterial pathogen. On the other hand, prodn. of BMAA or BMAA-contg. mols. by members of the human gut microbiota, for example by non-photosynthetic cyanobacteria, the Melainabacteria, remains only hypothetical. In any case, should BMAA reach the gut it may interact with cells of the mucosal immune system and neurons of the enteric nervous system (ENS) and possibly target the mitochondria. Here, we review the available evidence and hint on possible mechanisms by which chronic exposure to dietary sources of this microbial neurotoxin may drive protein misfolding and mitochondrial dysfunction with concomitant activation of innate immune responses, chronic low-grade gut inflammation, and ultimately the neurodegenerative features obsd. across the gut-brain axis in Parkinson's disease (PD).
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169Braak, H.; Rüb, U.; Gai, W. P.; Del Tredici, K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J. Neural Transm (Vienna) 2003, 110, 517– 536, DOI: 10.1007/s00702-002-0808-2Google Scholar169https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3s3gt1GltQ%253D%253D&md5=23ec33b5feb7fdb9b6959fc8d02f8205Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogenBraak H; Rub U; Gai W P; Del Tredici KJournal of neural transmission (Vienna, Austria : 1996) (2003), 110 (5), 517-36 ISSN:0300-9564.The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.
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170Wallen, Z. D.; Demirkan, A.; Twa, G.; Cohen, G.; Dean, M. N.; Standaert, D. G.; Sampson, T. R.; Payami, H. Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Nat. Commun. 2022, 13, 6958, DOI: 10.1038/s41467-022-34667-xGoogle Scholar170https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFWks7bP&md5=a13a8d0c27f697c48e0b43b90594ed2dMetagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanismsWallen, Zachary D.; Demirkan, Ayse; Twa, Guy; Cohen, Gwendolyn; Dean, Marissa N.; Standaert, David G.; Sampson, Timothy R.; Payami, HaydehNature Communications (2022), 13 (1), 6958CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resoln., using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide assocn. studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease assocn., network anal. to identify polymicrobial clusters, and functional profiling. Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-assocd. species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of mols. that induce alpha-synuclein pathol., and over-prodn. of toxicants; with the redn. in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were obsd. in exptl. models; reconcile and resolve human PD microbiome literature; and provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.
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171Vogt, N. M.; Kerby, R. L.; Dill-McFarland, K. A.; Harding, S. J.; Merluzzi, A. P.; Johnson, S. C.; Carlsson, C. M.; Asthana, S.; Zetterberg, H.; Blennow, K. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 2017, 7, 13537, DOI: 10.1038/s41598-017-13601-yGoogle Scholar171https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7is1CgsA%253D%253D&md5=d577a8c8a7b9ed5e83e5f2d9c3699ea0Gut microbiome alterations in Alzheimer's diseaseVogt Nicholas M; Harding Sandra J; Merluzzi Andrew P; Johnson Sterling C; Carlsson Cynthia M; Asthana Sanjay; Bendlin Barbara B; Kerby Robert L; Dill-McFarland Kimberly A; Rey Federico E; Johnson Sterling C; Carlsson Cynthia M; Asthana Sanjay; Johnson Sterling C; Carlsson Cynthia M; Bendlin Barbara B; Zetterberg Henrik; Blennow Kaj; Zetterberg Henrik; Blennow Kaj; Zetterberg Henrik; Zetterberg HenrikScientific reports (2017), 7 (1), 13537 ISSN:.Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
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172Zhuang, Z. Q.; Shen, L. L.; Li, W. W.; Fu, X.; Zeng, F.; Gui, L.; Lü, Y.; Cai, M.; Zhu, C.; Tan, Y. L. Gut Microbiota is Altered in Patients with Alzheimer’s Disease. J. Alzheimers Dis. 2018, 63, 1337– 1346, DOI: 10.3233/JAD-180176Google Scholar172https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MfjtVequg%253D%253D&md5=5d0d6c93eb43549ab5fa4c5c5ca3149eGut Microbiota is Altered in Patients with Alzheimer's DiseaseZhuang Zhen-Qian; Shen Lin-Lin; Li Wei-Wei; Zeng Fan; Zhu Chi; Li Hui-Yun; Zhu Jie; Zhou Hua-Dong; Bu Xian-Le; Wang Yan-Jiang; Fu Xue; Lu Yang; Gui Li; Cai Min; Tan Yin-Ling; Zheng PengJournal of Alzheimer's disease : JAD (2018), 63 (4), 1337-1346 ISSN:.Previous studies suggest that gut microbiota is associated with neuropsychiatric disorders, such as Parkinson's disease, amyotrophic lateral sclerosis, and depression. However, whether the composition and diversity of gut microbiota is altered in patients with Alzheimer's disease (AD) remains largely unknown. In the present study, we collected fecal samples from 43 AD patients and 43 age- and gender-matched cognitively normal controls. 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. The composition of gut microbiota was different between the two groups. Several bacteria taxa in AD patients were different from those in controls at taxonomic levels, such as Bacteroides, Actinobacteria, Ruminococcus, Lachnospiraceae, and Selenomonadales. Our findings suggest that gut microbiota is altered in AD patients and may be involved in the pathogenesis of AD.
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173Manderino, L.; Carroll, I.; Azcarate-Peril, M. A.; Rochette, A.; Heinberg, L.; Peat, C.; Steffen, K.; Mitchell, J.; Gunstad, J. Preliminary Evidence for an Association Between the Composition of the Gut Microbiome and Cognitive Function in Neurologically Healthy Older Adults. J. Int. Neuropsychol. Soc. 2017, 23, 700– 705, DOI: 10.1017/S1355617717000492Google Scholar173https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjgvFOhsA%253D%253D&md5=57f1fd37f2b71297b444efc7eb1cbe1dPreliminary Evidence for an Association Between the Composition of the Gut Microbiome and Cognitive Function in Neurologically Healthy Older AdultsManderino Lisa; Rochette Amber; Gunstad John; Carroll Ian; Azcarate-Peril M Andrea; Heinberg Leslie; Peat Christine; Steffen Kristine; Mitchell JamesJournal of the International Neuropsychological Society : JINS (2017), 23 (8), 700-705 ISSN:.OBJECTIVES: Dysbiosis of the gut microbiome is implicated in numerous human health conditions. Animal studies have linked microbiome disruption to changes in cognitive functioning, although no study has examined this possibility in neurologically healthy older adults. METHODS: Participants were 43 community-dwelling older adults (50-85 years) that completed a brief cognitive test battery and provided stool samples for gut microbiome sequencing. Participants performing≥1 SD below normative performance on two or more tests were compared to persons with one or fewer impaired scores. RESULTS: Mann Whitney U tests revealed different distributions of Bacteroidetes (p=.01), Firmicutes (p=.02), Proteobacteria (p=.04), and Verrucomicrobia (p=.003) between Intact and Impaired groups. These phyla were significantly correlated with cognitive test performances, particularly Verrucomicrobia and attention/executive function measures. CONCLUSIONS: The current findings suggest that composition of the gut microbiome is associated with cognitive test performance in neurologically healthy older adults. Future studies are needed to confirm these findings and explore possible mechanisms. (JINS, 2017, 23, 700-705).
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174Barbosa, R. S. D.; Vieira-Coelho, M. A. Probiotics and prebiotics: focus on psychiatric disorders - a systematic review. Nutr. Rev. 2020, 78, 437– 450, DOI: 10.1093/nutrit/nuz080Google Scholar174https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MfjsVajug%253D%253D&md5=5a4a8957e335389e7ab8be37cd83546eProbiotics and prebiotics: focus on psychiatric disorders - a systematic reviewBarbosa Renata S D; Vieira-Coelho Maria A; Vieira-Coelho Maria ANutrition reviews (2020), 78 (6), 437-450 ISSN:.CONTEXT: The gut-brain axis and microbial dysbiosis may play a role in psychiatric diseases. In this view, the gut microbiota has been considered a potential therapeutic target using probiotics and prebiotics. OBJECTIVE: This systematic review aims to find the existing clinical evidence that may justify the use of probiotics or prebiotics in psychiatric patients. DATA SOURCES: PRISMA guidelines were followed for a systematic literature review of randomized controlled trials that assessed the effect of prebiotics or probiotics in patients diagnosed with a classified psychiatric disorder. DATA EXTRACTION: From a total of 212 studies screened, 11 were included in the final systematic review. Quality assessment of the included trials was assessed by the Jadad scale. RESULTS: Probiotics seem to offer some benefit in major depressive disorder and Alzheimer's disease. One study showed that probiotics reduced rehospitalization in patients with acute mania. In autism spectrum disorders, the results were controversial; however a single study found that early administration of probiotics showed a preventive role. No benefits were found for patients with schizophrenia. In most studies, no major adverse effects were reported. CONCLUSIONS: Although recent findings in specific psychiatric disorders are encouraging, the use of prebiotics and probiotics in clinical practice stills lacks sufficiently robust evidence.
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175Ansari, F.; Pourjafar, H.; Tabrizi, A.; Homayouni, A. The Effects of Probiotics and Prebiotics on Mental Disorders: A Review on Depression, Anxiety, Alzheimer, and Autism Spectrum Disorders. Curr. Pharm. Biotechnol. 2020, 21, 555– 565, DOI: 10.2174/1389201021666200107113812Google Scholar175https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhslamsLrM&md5=9a728e9f22e2be662a4f20b3a96504ebThe effects of probiotics and prebiotics on mental disorders: a review on depression, anxiety, alzheimer, and autism spectrum disordersAnsari, Fereshteh; Pourjafar, Hadi; Tabrizi, Aydin; Homayouni, AzizCurrent Pharmaceutical Biotechnology (2020), 21 (7), 555-565CODEN: CPBUBP; ISSN:1389-2010. (Bentham Science Publishers Ltd.)A review. Background: Probiotics and their nutrient sources (prebiotics) have been shown to have pos. effects on different organs of the host. The idea of their potential benefits on Central Nervous Systems (CNS) and the incidence of Anxiety, Schizophrenia, Alzheimer, Depression, Autism, and other mental disorders has proposed a new category of medicines called "psychobiotic". Objective: In the current review, we present valuable insights into the complicated interactions between the GI microbiota (esp. in the colon), brain, immune and central nervous systems and provide a summary of the main findings of the effects of pro- and prebiotics on important mental disorders from the potential mechanisms of action to their application in clin. practice. Methods: The full text of potentially eligible studies was retrieved and assessed in detail by the reviewers. Results: The results of the provided evidence suggest that probiotic and prebiotics might improve mental function via several mechanisms. The beneficial effects of their application in Depression, Anxiety, Alzheimer and autism spectrum diseases have also been supported in clin. studies. Conclusion: Pro and prebiotics can improve mental health and psychol. function and can be offered as new medicines for common mental disorders, however, more clin. studies are necessary to conduct regarding the clin. significance of the effects and their bioequivalence or superiority against current treatments.
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176Messaoudi, M.; Lalonde, R.; Violle, N.; Javelot, H.; Desor, D.; Nejdi, A.; Bisson, J. F.; Rougeot, C.; Pichelin, M.; Cazaubiel, M. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr. 2011, 105, 755– 764, DOI: 10.1017/S0007114510004319Google Scholar176https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXitVOjsbo%253D&md5=ed9d1f4a7e88bad6f4a0d39c9e190f52Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjectsMessaoudi, Michael; Lalonde, Robert; Violle, Nicolas; Javelot, Herve; Desor, Didier; Nejdi, Amine; Bisson, Jean-Francois; Rougeot, Catherine; Pichelin, Matthieu; Cazaubiel, Murielle; Cazaubiel, Jean-MarcBritish Journal of Nutrition (2011), 105 (5), 755-764CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)In a previous clin. study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychol. distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclin. study, rats were daily administered PF for 2 wk and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clin. trial, volunteers participated in a double-blind, placebo-controlled, randomized parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behavior in rats (P < 0.05) and alleviated psychol. distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0.05; somatization, P < 0.05; depression, P < 0.05; and anger-hostility, P < 0.05), the HADS (HADS global score, P < 0.05; and HADS-anxiety, P < 0.06), and by the CCL (problem solving, P < 0.05) and the UFC level (P < 0.05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychol. effects in healthy human volunteers.
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177Akbari, E.; Asemi, Z.; Daneshvar Kakhaki, R.; Bahmani, F.; Kouchaki, E.; Tamtaji, O. R.; Hamidi, G. A.; Salami, M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Front. Aging Neurosci. 2016, 8, 256, DOI: 10.3389/fnagi.2016.00256Google Scholar177https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtV2isbjK&md5=564df5ccf68fedfde448510e4790165cEffect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trialAkbari, Elmira; Asemi, Zatollah; Kakhaki, Reza Daneshvar; Bahmani, Fereshteh; Kouchaki, Ebrahim; Tamtaji, Omid Reza; Hamidi, Gholam Ali; Salami, MahmoudFrontiers in Aging Neuroscience (2016), 8 (), 256/1-256/8CODEN: FANRC5; ISSN:1663-4365. (Frontiers Media S.A.)Alzheimer's disease (AD) is assocd. with severe cognitive impairments as well as some metabolic defects. Scant studies in animal models indicate a link between probiotics and cognitive function. This randomized, double-blind, and controlled clin. trial was conducted among 60 AD patients to assess the effects of probiotic supplementation on cognitive function and metabolic status. The patients were randomly divided into two groups (n = 30 in each group) treating with either milk (control group) or a mixt. of probiotics (probiotic group). The probiotic supplemented group took 200 mL/day probiotic milk contg. Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 CFU/g for each) for 12 wk. Mini-mental state examn. (MMSE) score was recorded in all subjects before and after the treatment. Pre- and post-treatment fasting blood samples were obtained to det. the related markers. After 12 wk intervention, compared with the control group (-5.03% ± 3.00), the probiotic treated (+27.90% ± 8.07) patients showed a significant improvement in the MMSE score (P < 0.001). In addn., changes in plasma malondialdehyde (-22.01% ± 4.84 vs. +2.67% ± 3.86 μmol/L, P < 0.001), serum high-sensitivity C-reactive protein (-17.61% ± 3.70 vs. +45.26% ± 3.50 μg/mL, P < 0.001), homeostasis model of assessment-estd. insulin resistance (+28.84% ± 13.34 vs. +76.95% ± 24.60, P = 0.002), Beta cell function (+3.45% ± 10.91 vs. +75.62% ± 23.18, P = 0.001), serum triglycerides (-20.29% ± 4.49 vs. -0.16% ± 5.24 mg/dL, P = 0.003), and quant. insulin sensitivity check index (-1.83 ± 1.26 vs. -4.66 ± 1.70, P = 0.006) in the probiotic group were significantly varied compared to the control group. We found that the probiotic treatment had no considerable effect on other biomarkers of oxidative stress and inflammation, fasting plasma glucose, and other lipid profiles. Overall, the current study demonstrated that probiotic consumption for 12 wk pos. affects cognitive function and some metabolic statuses in the AD patients.
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178Nimgampalle, M.; Kuna, Y. Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s Disease induced Albino Rats. J. Clin. Diagn. Res. 2017, 11, Kc01– kc05, DOI: 10.7860/JCDR/2017/26106.10428Google ScholarThere is no corresponding record for this reference.
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179Tamtaji, O. R.; Taghizadeh, M.; Daneshvar Kakhaki, R.; Kouchaki, E.; Bahmani, F.; Borzabadi, S.; Oryan, S.; Mafi, A.; Asemi, Z. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin. Nutr. 2019, 38, 1031– 1035, DOI: 10.1016/j.clnu.2018.05.018Google Scholar179https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFSgtr%252FP&md5=d1eeb5dea9fc4cabb4821be9e80c24f8Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trialTamtaji, Omid Reza; Taghizadeh, Mohsen; Daneshvar Kakhaki, Reza; Kouchaki, Ebrahim; Bahmani, Fereshteh; Borzabadi, Shokoofeh; Oryan, Shahrbanoo; Mafi, Alireza; Asemi, ZatollahClinical Nutrition (2019), 38 (3), 1031-1035CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)The investigation was done to assess the impacts of probiotic supplementation on movement and metabolic parameters in individuals with Parkinson's disease (PD).The study is randomized, double-blind, placebo-controlled clin. trial, which was done in sixty people with PD. Individuals were randomly divided into two groups in order to take either 8 × 109 CFU/day probiotic or placebo (n = 30 each group) that lasted 12 wk. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was recorded at pre- and post-intervention.Compared with the placebo, consuming probiotic decreased MDS-UPDRS (-4.8 ± 12.5 vs. +3.8 ± 13.0, P = 0.01). Probiotic supplementation also reduced high-sensitivity C-reactive protein (-1.6 ± 2.5 vs. +0.1 ± 0.3 mg/L, P < 0.001) and malondialdehyde (-0.2 ± 0.3 vs. +0.1 ± 0.3μmol/L, P = 0.006), and enhanced glutathione levels (+40.1 ± 81.5 vs. -12.1 ± 41.7μmol/L, P = 0.03) in comparison with the placebo. Addnl., probiotic consumption resulted in a statistically significant redn. in insulin levels (-2.1 ± 3.4 vs. +1.5 ± 5.1μIU/mL, P = 0.002) and insulin resistance (-0.5 ± 0.9 vs. +0.4 ± 1.2, P = 0.002), and a statistically significant rise in insulin sensitivity (+0.01 ± 0.02 vs. -0.006 ± 0.02, P = 0.01) in comparison with the placebo. Probiotic intake had no any significant impact on other metabolic profiles.Our study evidenced that 12 wk of probiotic consumption by individuals with PD had useful impacts on MDS-UPDRS and few metabolic profiles. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017082434497N4.
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180Frazier, K.; Chang, E. B. Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism. Trends Endocrinol Metab 2020, 31, 25– 36, DOI: 10.1016/j.tem.2019.08.013Google Scholar180https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslyqsbbO&md5=d1a714522940bc6ae225f017a09c51e1Intersection of the Gut Microbiome and Circadian Rhythms in MetabolismFrazier, Katya; Chang, Eugene B.Trends in Endocrinology and Metabolism (2020), 31 (1), 25-36CODEN: TENME4; ISSN:1043-2760. (Elsevier Ltd.)A review. The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiol. and metab. However, the mechanisms that underlie these observations remain largely unknown. Recent findings have implicated microbially derived mediators as potential signals between the gut microbiome and host circadian clocks; two specific mediators are discussed in this review: short-chain fatty acids (SCFAs) and bile acids (BAs). Key gaps in knowledge and major challenges that remain in the circadian and microbiome fields are also discussed, including animal vs. human models and the need for precise timed sample collection.
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181Gutierrez Lopez, D. E.; Lashinger, L. M.; Weinstock, G. M.; Bray, M. S. Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet. Cell Metab. 2021, 33, 873– 887, DOI: 10.1016/j.cmet.2021.03.015Google Scholar181https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXnslGitbY%253D&md5=55edf2c55d7b551bd0c74828f2caf50aCircadian rhythms and the gut microbiome synchronize the host metabolic response to dietGutierrez Lopez, Diana E.; Lashinger, Laura M.; Weinstock, George M.; Bray, Molly S.Cell Metabolism (2021), 33 (5), 873-887CODEN: CMEEB5; ISSN:1550-4131. (Elsevier Inc.)A review. The mol. circadian clock and symbiotic host-microbe relationships both evolved as mechanisms that enhance metabolic responses to environmental challenges. The gut microbiome benefits the host by breaking down diet-derived nutrients indigestible by the host and generating microbiota-derived metabolites that support host metab. Similarly, cellular circadian clocks optimize organismal physiol. to the environment by influencing the timing and coordination of metabolic processes. Host-microbe interactions are influenced by dietary quality and timing, as well as daily light/dark cycles that entrain circadian rhythms in the host. Together, the gut microbiome and the mol. circadian clock play a coordinated role in neural processing, metab., adipogenesis, inflammation, and disease initiation and progression. This examines the bidirectional interactions between the circadian clock, gut microbiota, and host metabolic systems and their effects on obesity and energy homeostasis. Directions for future research and the development of therapies that leverage these systems to address metabolic disease are highlighted.
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182Leng, Y.; Musiek, E. S.; Hu, K.; Cappuccio, F. P.; Yaffe, K. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019, 18, 307– 318, DOI: 10.1016/S1474-4422(18)30461-7Google Scholar182https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cflsFSnsg%253D%253D&md5=0816f7dd88b07bfa85b4b0f0f704c695Association between circadian rhythms and neurodegenerative diseasesLeng Yue; Musiek Erik S; Hu Kun; Cappuccio Francesco P; Yaffe KristineThe Lancet. Neurology (2019), 18 (3), 307-318 ISSN:.Dysfunction in 24-h circadian rhythms is a common occurrence in ageing adults; however, circadian rhythm disruptions are more severe in people with age-related neurodegenerative diseases, including Alzheimer's disease and related dementias, and Parkinson's disease. Manifestations of circadian rhythm disruptions differ according to the type and severity of neurodegenerative disease and, for some patients, occur before the onset of typical clinical symptoms of neurodegeneration. Evidence from preliminary studies suggest that circadian rhythm disruptions, in addition to being a symptom of neurodegeneration, might also be a potential risk factor for developing Alzheimer's disease and related dementias, and Parkinson's disease, although large, longitudinal studies are needed to confirm this relationship. The mechanistic link between circadian rhythms and neurodegeneration is still not fully understood, although proposed underlying pathways include alterations of protein homoeostasis and immune and inflammatory function. While preliminary clinical studies are promising, more studies of circadian rhythm disruptions and its mechanisms are required. Furthermore, clinical trials are needed to determine whether circadian interventions could prevent or delay the onset of neurodegenerative diseases.
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183Leone, V.; Gibbons, S. M.; Martinez, K.; Hutchison, A. L.; Huang, E. Y.; Cham, C. M.; Pierre, J. F.; Heneghan, A. F.; Nadimpalli, A.; Hubert, N. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe 2015, 17, 681– 689, DOI: 10.1016/j.chom.2015.03.006Google Scholar183https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXms1yntrk%253D&md5=56dd299db5987fa956049b7513edb0e6Effects of Diurnal Variation of Gut Microbes and High-Fat Feeding on Host Circadian Clock Function and MetabolismLeone, Vanessa; Gibbons, Sean M.; Martinez, Kristina; Hutchison, Alan L.; Huang, Edmond Y.; Cham, Candace M.; Pierre, Joseph F.; Heneghan, Aaron F.; Nadimpalli, Anuradha; Hubert, Nathaniel; Zale, Elizabeth; Wang, Yunwei; Huang, Yong; Theriault, Betty; Dinner, Aaron R.; Musch, Mark W.; Kudsk, Kenneth A.; Prendergast, Brian J.; Gilbert, Jack A.; Chang, Eugene B.Cell Host & Microbe (2015), 17 (5), 681-689CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)Circadian clocks and metab. are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an addnl. key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain wt. compared to conventionally raised counterparts. Examn. of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary compn. Addnl., specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.
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184Nicholson, J. K.; Holmes, E.; Kinross, J.; Burcelin, R.; Gibson, G.; Jia, W.; Pettersson, S. Host-gut microbiota metabolic interactions. Science 2012, 336, 1262– 1267, DOI: 10.1126/science.1223813Google Scholar184https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnvFekt7c%253D&md5=a4383140dbfa427c36adb44d30add530Host-Gut Microbiota Metabolic InteractionsNicholson, Jeremy K.; Holmes, Elaine; Kinross, James; Burcelin, Remy; Gibson, Glenn; Jia, Wei; Pettersson, SvenScience (Washington, DC, United States) (2012), 336 (6086), 1262-1267CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. The compn. and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiol. connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
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185Moran, C. P.; Shanahan, F. Gut microbiota and obesity: role in aetiology and potential therapeutic target. Best Pract. Res. Clin. Gastroenterol. 2014, 28, 585– 597, DOI: 10.1016/j.bpg.2014.07.005Google Scholar185https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1SjsLrN&md5=e1e2e003162e3d957e19b1b2e3dd71e3Gut microbiota and obesity: Role in aetiology and potential therapeutic targetMoran, Carthage P.; Shanahan, FergusBest Practice & Research, Clinical Gastroenterology (2014), 28 (4), 585-597CODEN: BPRCB6 ISSN:. (Elsevier Ltd.)Obesity is epidemic; chronic energy surplus is clearly important in obesity development but other factors are at play. Indigenous gut microbiota are implicated in the aetiopathogenesis of obesity and obesity-related disorders. Evidence from murine models initially suggested a role for the gut microbiota in wt. regulation and the microbiota has been shown to contribute to the low grade inflammation that characterises obesity. The microbiota and its metabolites mediate some of the alterations of the microbiota-gut-brain axis, the endocannabinoid system, and bile acid metab., found in obesity-related disorders. Modulation of the gut microbiota is an attractive proposition for prevention or treatment of obesity, particularly as traditional measures have been sub-optimal.
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186Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012, 490, 55– 60, DOI: 10.1038/nature11450Google Scholar186https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVaqt7fJ&md5=96d88e053af22d9b82d8d96dfab6a147A metagenome-wide association study of gut microbiota in type 2 diabetesQin, Junjie; Li, Yingrui; Cai, Zhiming; Li, Shenghui; Zhu, Jianfeng; Zhang, Fan; Liang, Suisha; Zhang, Wenwei; Guan, Yuanlin; Shen, Dongqian; Peng, Yangqing; Zhang, Dongya; Jie, Zhuye; Wu, Wenxian; Qin, Youwen; Xue, Wenbin; Li, Junhua; Han, Lingchuan; Lu, Donghui; Wu, Peixian; Dai, Yali; Sun, Xiaojuan; Li, Zesong; Tang, Aifa; Zhong, Shilong; Li, Xiaoping; Chen, Weineng; Xu, Ran; Wang, Mingbang; Feng, Qiang; Gong, Meihua; Yu, Jing; Zhang, Yanyan; Zhang, Ming; Hansen, Torben; Sanchez, Gaston; Raes, Jeroen; Falony, Gwen; Okuda, Shujiro; Almeida, Mathieu; LeChatelier, Emmanuelle; Renault, Pierre; Pons, Nicolas; Batto, Jean-Michel; Zhang, Zhaoxi; Chen, Hua; Yang, Ruifu; Zheng, Weimou; Li, Songgang; Yang, Huanming; Wang, Jian; Ehrlich, S. Dusko; Nielsen, Rasmus; Pedersen, Oluf; Kristiansen, Karsten; Wang, JunNature (London, United Kingdom) (2012), 490 (7418), 55-60CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out anal. on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide assocn. study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approx. 60,000 type-2-diabetes-assocd. markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS anal. showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulfate redn. and oxidative stress resistance. An anal. of 23 addnl. individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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187Donohoe, D. R.; Wali, A.; Brylawski, B. P.; Bultman, S. J. Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes. PLoS One 2012, 7, e46589, DOI: 10.1371/journal.pone.0046589Google Scholar187https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFSktrfP&md5=b6ece252ef812a4b2d023eb11283a448Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytesDonohoe, Dallas R.; Wali, Aminah; Brylawski, Bruna P.; Bultman, Scott J.PLoS One (2012), 7 (9), e46589CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)A prodigious no. of microbes inhabit the human body, esp. in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metab., we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germ-free and conventionally-raised C57BL/6 mice. These expts. demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germ-free colonocytes. However, 13C-glucose metabolic-flux expts. and biochem. assays demonstrated that they shifted their glucose metab. away from mitochondrial oxidn./CO2 prodn. and toward increased glycolysis/lactate prodn., which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH) levels and activity. Consistent with perturbed PDH function, the addn. of butyrate, but not glucose, to germ-free colonocytes ex vivo stimulated oxidative metab. As a result of this energetic defect, germ-free colonocytes exhibited a partial block in the G1-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells.
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188Donohoe, D. R.; Garge, N.; Zhang, X.; Sun, W.; O’Connell, T. M.; Bunger, M. K.; Bultman, S. J. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011, 13, 517– 526, DOI: 10.1016/j.cmet.2011.02.018Google Scholar188https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsFalsro%253D&md5=e2df41177d98df47115844f10c2a07fdThe Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian ColonDonohoe, Dallas R.; Garge, Nikhil; Zhang, Xinxin; Sun, Wei; O'Connell, Thomas M.; Bunger, Maureen K.; Bultman, Scott J.Cell Metabolism (2011), 13 (5), 517-526CODEN: CMEEB5; ISSN:1550-4131. (Cell Press)Summary: The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metab. in a general vs. tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germ-free mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metab. including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD+, oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27kip1 phosphorylation, and autophagy. When butyrate is added to germ-free colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor.
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189Tolhurst, G.; Heffron, H.; Lam, Y. S.; Parker, H. E.; Habib, A. M.; Diakogiannaki, E.; Cameron, J.; Grosse, J.; Reimann, F.; Gribble, F. M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012, 61, 364– 371, DOI: 10.2337/db11-1019Google Scholar189https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XltVOlt7Y%253D&md5=fa3f45e6f2dd3b88b217700febe3248fShort-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2Tolhurst, Gwen; Heffron, Helen; Lam, Yu Shan; Parker, Helen E.; Habib, Abdella M.; Diakogiannaki, Eleftheria; Cameron, Jennifer; Grosse, Johannes; Reimann, Frank; Gribble, Fiona M.Diabetes (2012), 61 (2), 364-371CODEN: DIAEAZ; ISSN:0012-1797. (American Diabetes Association, Inc.)Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermn. of "indigestible" prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quant. PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1-secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.
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190de Vos, W. M.; Tilg, H.; Van Hul, M.; Cani, P. D. Gut microbiome and health: mechanistic insights. Gut 2022, 71, 1020– 1032, DOI: 10.1136/gutjnl-2021-326789Google Scholar190https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsFSrs73L&md5=e2b02488e750468564ab871ae5955b8fGut microbiome and health: mechanistic insightsde Vos, Willem M.; Tilg, Herbert; Van Hul, Matthias; Cani, Patrice D.Gut (2022), 71 (5), 1020-1032CODEN: GUTTAK; ISSN:0017-5749. (BMJ)A review. The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of mol. tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metab. are affected. In this review, specific attention is given to provide a crit. evaluation of the current understanding in this field. Numerous mol. mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, shortchain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified mol. actors (ie, endocannabinoids, bioactive lipids, phenolicderived compds., advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5). Altogether, understanding the complexity and the mol. aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.
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191Yeoh, Y. K.; Zuo, T.; Lui, G. C.-Y.; Zhang, F.; Liu, Q.; Li, A. Y.; Chung, A. C.; Cheung, C. P.; Tso, E. Y.; Fung, K. S. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021, 70, 698– 706, DOI: 10.1136/gutjnl-2020-323020Google Scholar191https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtFegtLjK&md5=f488d7a24c822e82b9c627d96687ab09Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19Yeoh, Yun Kit; Zuo, Tao; Lui, Grace Chung-Yan; Zhang, Fen; Liu, Qin; Li, Amy Yl; Chung, Arthur Ck; Cheung, Chun Pan; Tso, Eugene Yk; Fung, Kitty Sc; Chan, Veronica; Ling, Lowell; Joynt, Gavin; Hui, David Shu-Cheong; Chow, Kai Ming; Ng, Susanna So Shan; Li, Timothy Chun-Man; Ng, Rita Wy; Yip, Terry Cf; Wong, Grace Lai-Hung; Chan, Francis Kl; Wong, Chun Kwok; Chan, Paul Ks; Ng, Siew C.Gut (2021), 70 (4), 698-706CODEN: GUTTAK; ISSN:0017-5749. (BMJ)Objective: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome compn., if any, resolve with clearance of the SARS-CoV-2 virus. Methods: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with lab.-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compns. were characterised by shotgun sequencing total DNA extd. from stools. Concns. of inflammatory cytokines and blood markers were measured from plasma. Results: Gut microbiome compn. was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irresp. of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resoln. Moreover, this perturbed compn. exhibited stratification with disease severity concordant with elevated concns. of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. Conclusion: Assocns. between gut microbiota compn., levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resoln. could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
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192Burchill, E.; Lymberopoulos, E.; Menozzi, E.; Budhdeo, S.; McIlroy, J. R.; Macnaughtan, J.; Sharma, N. The Unique Impact of COVID-19 on Human Gut Microbiome Research. Frontiers in Medicine 2021, 8, 652464, DOI: 10.3389/fmed.2021.652464Google Scholar192https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sflt1Sgtg%253D%253D&md5=2f2093b61f3af7cda6158315aa0b2a39The Unique Impact of COVID-19 on Human Gut Microbiome ResearchBurchill Ella; Lymberopoulos Eva; Menozzi Elisa; Budhdeo Sanjay; Sharma Nikhil; Lymberopoulos Eva; Budhdeo Sanjay; Sharma Nikhil; McIlroy James R; Macnaughtan JaneFrontiers in medicine (2021), 8 (), 652464 ISSN:2296-858X.The coronavirus (COVID-19) pandemic has disrupted clinical trials globally, with unique implications for research into the human gut microbiome. In this mini-review, we explore the direct and indirect influences of the pandemic on the gut microbiome and how these can affect research and clinical trials. We explore the direct bidirectional relationships between the COVID-19 virus and the gut and lung microbiomes. We then consider the significant indirect effects of the pandemic, such as repeated lockdowns, increased hand hygiene, and changes to mood and diet, that could all lead to longstanding changes to the gut microbiome at an individual and a population level. Together, these changes may affect long term microbiome research, both in observational as well as in population studies, requiring urgent attention. Finally, we explore the unique implications for clinical trials using faecal microbiota transplants (FMT), which are increasingly investigated as potential treatments for a range of diseases. The pandemic introduces new barriers to participation in trials, while the direct and indirect effects laid out above can present a confounding factor. This affects recruitment and sample size, as well as study design and statistical analyses. Therefore, the potential impact of the pandemic on gut microbiome research is significant and needs to be specifically addressed by the research community and funders.
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193Bernard-Raichon, L.; Venzon, M.; Klein, J.; Axelrad, J. E.; Zhang, C.; Sullivan, A. P.; Hussey, G. A.; Casanovas-Massana, A.; Noval, M. G.; Valero-Jimenez, A. M. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nat. Commun. 2022, 13, 5926, DOI: 10.1038/s41467-022-33395-6Google Scholar193https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xisl2htLnL&md5=d101841387bc8b27c1a0a3f8a7ae843bGut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremiaBernard-Raichon, Lucie; Venzon, Mericien; Klein, Jon; Axelrad, Jordan E.; Zhang, Chenzhen; Sullivan, Alexis P.; Hussey, Grant A.; Casanovas-Massana, Arnau; Noval, Maria G.; Valero-Jimenez, Ana M.; Gago, Juan; Putzel, Gregory; Pironti, Alejandro; Wilder, Evan; Yale IMPACT Research Team; Thorpe, Lorna E.; Littman, Dan R.; Dittmann, Meike; Stapleford, Kenneth A.; Shopsin, Bo; Torres, Victor J.; Ko, Albert I.; Iwasaki, Akiko; Cadwell, Ken; Schluter, JonasNature Communications (2022), 13 (1), 5926CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Although microbial populations in the gut microbiome are assocd. with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is assocd. with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clin. sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Anal. of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.
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194Chumpitazi, B. P. The gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disorders. Curr. Opin. Gastroenterol. 2020, 36, 147– 154, DOI: 10.1097/MOG.0000000000000608Google Scholar194https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MbhsVyqsA%253D%253D&md5=46619e9dfa4b6fe5b22d6fb770354f1aThe gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disordersChumpitazi Bruno P; Chumpitazi Bruno PCurrent opinion in gastroenterology (2020), 36 (2), 147-154 ISSN:.PURPOSE OF REVIEW: Fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) dietary restriction ameliorates irritable bowel syndrome (IBS) symptoms; however, not all individuals with IBS respond. Given the gut microbiome's role in carbohydrate fermentation, investigators have evaluated whether the gut microbiome may predict low FODMAP diet efficacy. RECENT FINDINGS: Gut microbiome fermentation, even to the same carbohydrate, is not uniform across all individuals with several factors (e.g. composition) playing a role. In both children and adults with IBS, studies are emerging suggesting the gut microbiome may predict low FODMAP diet efficacy. However, there is significant heterogeneity in the approaches (study population, microbiome assessment methods, statistical techniques, etc.) used amongst these studies. SUMMARY: The gut microbiome holds promise as a predictor of low FODMAP diet efficacy. However, further investigation using standardized approaches to evaluate the microbiome while concomitantly assessing other potential predictors are needed to more rigorously evaluate this area.
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195Leshem, A.; Segal, E.; Elinav, E. The Gut Microbiome and Individual-Specific Responses to Diet. mSystems 2020, 5, e00665– 00620, DOI: 10.1128/mSystems.00665-20Google Scholar195https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXis1ensb%252FL&md5=7233b2ed6a68e52d8a48f7748b4bd049The gut microbiome and individual-specific responses to dietLeshem, Avner; Segal, Eran; Elinav, EranmSystems (2020), 5 (5), e00665CODEN: MSYSBR; ISSN:2379-5077. (American Society for Microbiology)Nutritional content and timing are increasingly appreciated to constitute important human variables collectively impacting all aspects of human physiol. and disease. However, person-specific mechanisms driving nutritional impacts on the human host remain incompletely understood, while current dietary recommendations remain empirical and nonpersonalized. Precision nutrition aims to harness individualized bodies of data, including the human gut microbiome, in predicting person-specific physiol. responses (such as glycemic responses) to food. With these advances notwithstanding, many unknowns remain, including the long-term efficacy of such interventions in delaying or reversing human metabolic disease, mechanisms driving these dietary effects, and the extent of the contribution of the gut microbiome to these processes. We summarize these conceptual advances, while highlighting challenges and means of addressing them in the next decade of study of precision medicine, toward generation of insights that may help to evolve precision nutrition as an effective future tool in a variety of "multifactorial" human disorders.
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196Lepage, P.; Häsler, R.; Spehlmann, M. E.; Rehman, A.; Zvirbliene, A.; Begun, A.; Ott, S.; Kupcinskas, L.; Doré, J.; Raedler, A. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 2011, 141, 227– 236, DOI: 10.1053/j.gastro.2011.04.011Google Scholar196https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MnltV2lsw%253D%253D&md5=4967b06bdc3199066a51d166b172a9dbTwin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitisLepage Patricia; Hasler Robert; Spehlmann Martina E; Rehman Ateequr; Zvirbliene Aida; Begun Alexander; Ott Stephan; Kupcinskas Limas; Dore Joel; Raedler Andreas; Schreiber StefanGastroenterology (2011), 141 (1), 227-36 ISSN:.BACKGROUND & AIMS: Interactions between genetic and environmental factors are believed to be involved in onset and initiation of inflammatory bowel disease. We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium. METHODS: Biopsy were collected from sigmoid colon of UC patients and their healthy twins (discordant twin pairs) and from twins without UC. Microbiota profiles were determined from analysis of 16S ribosomal DNA libraries; messenger RNA profiles were determined by microarray analysis. RESULTS: Patients with UC had dysbiotic microbiota, characterized by less bacterial diversity and more Actinobacteria and Proteobacteria than that of their healthy siblings; healthy siblings from discordant twins had more bacteria from the Lachnospiraceae and Ruminococcaceae families than twins who were both healthy. In twins who were both healthy, 34 mucosal transcripts correlated with bacterial genera, whereas only 25 and 11 correlated with bacteria genera in healthy individuals and their twins with UC, respectively. Transcripts related to oxidative and immune responses were differentially expressed between patients with UC and their healthy twins. CONCLUSIONS: The transcriptional profile of the mucosa appears to interact with the colonic microbiota; this interaction appears to be lost in colon of patients with UC. Bacterial functions, such as butyrate production, might affect mucosal gene expression. Patients with UC had different gene expression profiles and lower levels of biodiversity than their healthy twins, as well as unusual aerobic bacteria. Patients with UC had lower percentages of potentially protective bacterial species than their healthy twins.
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197Manichanh, C.; Borruel, N.; Casellas, F.; Guarner, F. The gut microbiota in IBD. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 599– 608, DOI: 10.1038/nrgastro.2012.152Google Scholar197https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVKmurvN&md5=356ec8125e30b70feafb5b7570c843deThe gut microbiota in IBDManichanh, Chaysavanh; Borruel, Natalia; Casellas, Francesc; Guarner, FranciscoNature Reviews Gastroenterology & Hepatology (2012), 9 (10), 599-608CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. IBD-ulcerative colitis and Crohn's disease-is emerging as a worldwide epidemic. An assocn. between the increased incidence of IBD and environmental factors linked to socioeconomic development has been persistently detected in different parts of the world. The lifestyle in developed countries might impair the natural patterns of microbial colonization of the human gut. The interaction of microbes with mucosal immune compartments in the gut seems to have a major role in priming and regulating immunity. In IBD, mucosal lesions are generated by an excessive or dysregulated immune response against commensal microbes in the gut. In individuals with a genetic susceptibility to IBD, abnormal microbial colonization of the gastrointestinal tract might be the origin of such dysregulation. Developments in gene-sequencing technologies, as well as increased availability of powerful bioinformatic tools, have enabled novel insights into the microbial compn. of the human gut microbiota and the effect of microbial communities on human physiol. and disease. Studies that used these technologies indicate that dysbiosis (i.e., abnormal microbiota compn.) and decreased complexity of the gut microbial ecosystem are common features in patients with Crohn's disease or ulcerative colitis. Whether such changes are a cause or a consequence of the disease remains to be elucidated.
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198Tong, M.; Li, X.; Wegener Parfrey, L.; Roth, B.; Ippoliti, A.; Wei, B.; Borneman, J.; McGovern, D. P.; Frank, D. N.; Li, E. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One 2013, 8, e80702, DOI: 10.1371/journal.pone.0080702Google Scholar198https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtlyltw%253D%253D&md5=d5dd9ca97aca3f3fcfd9e39b22785b5cA modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel diseaseTong, Maomeng; Li, Xiaoxiao; Parfrey, Laura Wegener; Roth, Bennett; Ippoliti, Andrew; Wei, Bo; Borneman, James; McGovern, Dermot P. B.; Frank, Daniel N.; Li, Ellen; Horvath, Steve; Knight, Rob; Braun, JonathanPLoS One (2013), 8 (11), e80702/1-e80702/14CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial compn. are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecol. analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quant. reproducible features of microbial compn. in normal and IBD mucosa. We sequenced 16S rRNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clin. remission). CD and UC patients showed a redn. in phylogenetic diversity and shifts in microbial compn., comparable to previous studies using conventional mucosal biopsies. Anal. of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals and their compn. and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were assocd. with healthy, CD or UC disease states. Imputed metagenome anal. indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metab. pathways relevant to host-pathogen interaction in the disease-assocd. modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecol. relevant to IBD.
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199Guinane, C. M.; Cotter, P. D. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap. Adv. Gastroenterol. 2013, 6, 295– 308, DOI: 10.1177/1756283X13482996Google Scholar199https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sjmsFGltQ%253D%253D&md5=af7a6aea1965ce4b76dd186765f08f9fRole of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organGuinane Caitriona M; Cotter Paul DTherapeutic advances in gastroenterology (2013), 6 (4), 295-308 ISSN:1756-283X.The human gut microbiota has become the subject of extensive research in recent years and our knowledge of the resident species and their potential functional capacity is rapidly growing. Our gut harbours a complex community of over 100 trillion microbial cells which influence human physiology, metabolism, nutrition and immune function while disruption to the gut microbiota has been linked with gastrointestinal conditions such as inflammatory bowel disease and obesity. Here, we review the many significant recent studies that have centred on further enhancing our understanding of the complexity of intestinal communities as well as their genetic and metabolic potential. These have provided important information with respect to what constitutes a 'healthy gut microbiota' while furthering our understanding of the role of gut microbes in intestinal diseases. We also highlight recently developed genomic and other tools that are used to study the gut microbiome and, finally, we consider the manipulation of the gut microbiota as a potential therapeutic option to treat chronic gastrointestinal disease.
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200Kassam, Z.; Lee, C. H.; Yuan, Y.; Hunt, R. H. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am. J. Gastroenterol. 2013, 108, 500– 508, DOI: 10.1038/ajg.2013.59Google Scholar200https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3svnvVKmtQ%253D%253D&md5=9bcde5d19419ee5dc5752e597c14b057Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysisKassam Zain; Lee Christine H; Yuan Yuhong; Hunt Richard HThe American journal of gastroenterology (2013), 108 (4), 500-8 ISSN:.OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI. METHODS: An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups. RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2)=33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI -0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years. CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
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201Tang, W. H.; Kitai, T.; Hazen, S. L. Gut Microbiota in Cardiovascular Health and Disease. Circ. Res. 2017, 120, 1183– 1196, DOI: 10.1161/CIRCRESAHA.117.309715Google Scholar201https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlt1ens7g%253D&md5=5ff9db227ee9ce736705587ad43ae882Gut Microbiota in Cardiovascular Health and DiseaseTang, W. H. Wilson; Kitai, Takeshi; Hazen, Stanley L.Circulation Research (2017), 120 (7), 1183-1196CODEN: CIRUAL; ISSN:0009-7330. (Lippincott Williams & Wilkins)Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the compn. of gut microbiota assocd. with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addn. to alterations in gut microbiota compn., the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiol. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N-oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addn. to these metab.-dependent pathways, metab.-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure-assocd. splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiol. and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.
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202Jiang, H. Y.; Zhang, X.; Yu, Z. H.; Zhang, Z.; Deng, M.; Zhao, J. H.; Ruan, B. Altered gut microbiota profile in patients with generalized anxiety disorder. J. Psychiatr. Res. 2018, 104, 130– 136, DOI: 10.1016/j.jpsychires.2018.07.007Google Scholar202https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c7gt1Kqsw%253D%253D&md5=cd4cd04e4c92d8d72dbd3f497c468f40Altered gut microbiota profile in patients with generalized anxiety disorderJiang Hai-Yin; Zhang Xue; Deng Min; Yu Zheng-He; Zhang Zhe; Zhao Jian-Hua; Ruan BingJournal of psychiatric research (2018), 104 (), 130-136 ISSN:.Close relationships have recently been established between gut microbiota and some mental disorders. Here, we performed a systematic comparative analysis of the gut microbiome in patients with generalized anxiety disorder (GAD) and healthy controls (HCs). We first conducted a cross-sectional study of 40 patients with GAD in the active state and 36 HCs. Second, subgroup analysis consisting of 12 antidepressant-naive patients and 22 controls was performed to validate the results. Finally, a prospective study was performed in a subgroup of nine patients with GAD who underwent analysis in the active state of anxiety and in remission. Compared with the HCs, we found markedly decreased microbial richness and diversity, distinct metagenomic composition with reduced short-chain fatty acid (SCFA)-producing bacteria (associated with a healthy status) and overgrowth of bacteria, such as Escherichia-Shigella, Fusobacterium and Ruminococcus gnavus. Unexpectedly, these changes in the genera were not reversed in remissive GAD. This study identified microbiota dysbiosis of gut microbiota in GAD patients, suggesting that targeting the microbiome may be a useful therapeutic and preventive target for GAD.
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203Chen, Y. H.; Bai, J.; Wu, D.; Yu, S. F.; Qiang, X. L.; Bai, H.; Wang, H. N.; Peng, Z. W. Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. J. Affect. Disord. 2019, 259, 56– 66, DOI: 10.1016/j.jad.2019.08.014Google Scholar203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1art7%252FO&md5=f4453fa8729d92eaee7c4c0514840797Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment responseChen, Yi-huan; Bai, Jie; Wu, Di; Yu, Shou-fen; Qiang, Xiao-ling; Bai, Hua; Wang, Hua-ning; Peng, Zheng-wuJournal of Affective Disorders (2019), 259 (), 56-66CODEN: JADID7; ISSN:0165-0327. (Elsevier Inc.)Assocns. between abnormal gut microbiome compns. and anxiety-like behaviors are well established. However, it is unknown whether the gut microbiome compn. is assocd. with the severity of generalized anxiety disorder (GAD) and relief from clin. symptoms in patients. Stool samples from 36 patients with active GAD (A-GAD group) and 24 matched healthy control subjects (HC group) were analyzed by 16S rRNA gene sequencing. Anxiety was assessed with the Hamilton Anxiety Rating Scale and the Self-rating Anxiety Scale, and global assessments of functioning were performed at baseline and 1 mo after drug treatment. Gut microbiome compns. were altered in A-GAD patients, with fewer operational taxonomic units and lower fecal bacterial α-diversity. Specifically, Firmicutes and Tenericutes abundances were lower in A-GAD patients, and several genera were differentially represented in the A-GAD and HC groups. The abundances of Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, and Prevotella_9 correlated neg. with the anxiety severity and pos. with anxiety redn., whereas the abundances of Bacteroides and Escherichia-Shigella were pos. assocd. with anxiety severity. The sample sizes were small and the stool samples were collected only at baseline therefore, a causal assocn. between changes in intestinal flora and disease remission was not established. Altered gut microbiome compn. may contribute to GAD pathogenesis and remission.
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204Hemmings, S. M. J.; Malan-Müller, S.; van den Heuvel, L. L.; Demmitt, B. A.; Stanislawski, M. A.; Smith, D. G.; Bohr, A. D.; Stamper, C. E.; Hyde, E. R.; Morton, J. T. The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study. Psychosom. Med. 2017, 79, 936– 946, DOI: 10.1097/PSY.0000000000000512Google Scholar204https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjmvVCmsw%253D%253D&md5=13291869f8793210e263a4abfa875e97The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory StudyHemmings Sian M J; Malan-Muller Stefanie; van den Heuvel Leigh L; Demmitt Brittany A; Stanislawski Maggie A; Smith David G; Bohr Adam D; Stamper Christopher E; Hyde Embriette R; Morton James T; Marotz Clarisse A; Siebler Philip H; Braspenning Maarten; Van Criekinge Wim; Hoisington Andrew J; Brenner Lisa A; Postolache Teodor T; McQueen Matthew B; Krauter Kenneth S; Knight Rob; Seedat Soraya; Lowry Christopher APsychosomatic medicine (2017), 79 (8), 936-946 ISSN:.OBJECTIVE: Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls to identify potential differences in microbial diversity or microbial community structure. METHODS: The Clinician-Administered PTSD Scale for DSM-5 was used to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA gene V3/V4 amplicons were generated and sequenced. Microbial community structure, α-diversity, and β-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD. RESULTS: There were no differences between PTSD and TE control groups in α- or β-diversity measures (e.g., α-diversity: Shannon index, t = 0.386, p = .70; β-diversity, on the basis of analysis of similarities: Bray-Curtis test statistic = -0.033, p = .70); however, random forest analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher Clinician-Administered PTSD Scale scores (r = -0.387, p = .035). CONCLUSIONS: In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.
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205Stevens, B. R.; Goel, R.; Seungbum, K.; Richards, E. M.; Holbert, R. C.; Pepine, C. J.; Raizada, M. K. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut 2018, 67, 1555– 1557, DOI: 10.1136/gutjnl-2017-314759Google Scholar205https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvVKlsLk%253D&md5=99b454cb63378624dd008fcce23b1593Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depressionStevens, Bruce R.; Goel, Ruby; Seungbum, Kim; Richards, Elaine M.; Holbert, Richard C.; Pepine, Carl J.; Raizada, Mohan K.Gut (2018), 67 (8), 1555-1557CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)This article relates to increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression .
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206Kelly, J. R.; Borre, Y.; O'Brien, C.; Patterson, E.; El Aidy, S.; Deane, J.; Kennedy, P. J.; Beers, S.; Scott, K.; Moloney, G. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J. Psychiatr. Res. 2016, 82, 109– 118, DOI: 10.1016/j.jpsychires.2016.07.019Google Scholar206https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3nsFalsw%253D%253D&md5=508851100916cd45c333e8f2eb862c2dTransferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the ratKelly John R; Clarke Gerard; Borre Yuliya; Kennedy Paul J; Beers Sasja; Scott Karen; Moloney Gerard; Hoban Alan E; Fitzgerald Patrick; O' Brien Ciaran; Patterson Elaine; El Aidy Sahar; Deane Jennifer; Ross Paul; Stanton Catherine; Scott Lucinda; Cryan John F; Dinan Timothy GJournal of psychiatric research (2016), 82 (), 109-18 ISSN:.The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
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207Lin, P.; Ding, B.; Feng, C.; Yin, S.; Zhang, T.; Qi, X.; Lv, H.; Guo, X.; Dong, K.; Zhu, Y. Prevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorder. J. Affect. Disord. 2017, 207, 300– 304, DOI: 10.1016/j.jad.2016.09.051Google Scholar207https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2srgtl2isw%253D%253D&md5=abf902c0dc205474615200100340069ePrevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorderLin Ping; Ding Bingyu; Feng Chunyan; Yin Shuwei; Zhang Ting; Qi Xin; Lv Huiying; Guo Xiaokui; Dong Ke; Zhu Yongzhang; Li QingtianJournal of affective disorders (2017), 207 (), 300-304 ISSN:.BACKGROUND: The diagnosis of major depression disorder (MDD) and other mental disorders were depended on some subjective survey scales. There are confirmed relationship between the gut flora and the mental states of MDD patients. METHODS: The V3-V4 region of the 16S rRNA gene was extracted from the fecal microbial communities in MDD patients, PCR amplified and sequenced on the Illumina Miseq platform. RESULTS: More phylum Firmicutes, less Bacteroidetes, and more genus Prevotella, Klebsiella, Streptococcus and Clostridium XI were found in MDD patients. The changes of the proportion of Prevotella and Klebsiella were consistent with Hamilton depression rating scale. LIMITATIONS: The conclusion was limited by small sample sizes and potential uncontrollable influence factors on fecal microbiota. DISCUSSION: Prevotella and Klebsiella proportion in fecal microbial communities should be concerned in the diagnosis and therapeutic monitoring of MDD in future.
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208Gough, E.; Shaikh, H.; Manges, A. R. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin. Infect. Dis. 2011, 53, 994– 1002, DOI: 10.1093/cid/cir632Google Scholar208https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3Mbhs1emsA%253D%253D&md5=323ed1a1e99f6c06f7c045c917ed5945Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infectionGough Ethan; Shaikh Henna; Manges Amee RClinical infectious diseases : an official publication of the Infectious Diseases Society of America (2011), 53 (10), 994-1002 ISSN:.Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.
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209Craciun, C. I.; Neag, M. A.; Catinean, A.; Mitre, A. O.; Rusu, A.; Bala, C.; Roman, G.; Buzoianu, A. D.; Muntean, D. M.; Craciun, A. E. The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus. Biomedicines 2022, 10, 308, DOI: 10.3390/biomedicines10020308Google Scholar209https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XlsFars7g%253D&md5=c673653b5e07d22dc660deb87be09dbeThe Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes MellitusCraciun, Cristian-Ioan; Neag, Maria-Adriana; Catinean, Adrian; Mitre, Andrei-Otto; Rusu, Adriana; Bala, Cornelia; Roman, Gabriela; Buzoianu, Anca-Dana; Muntean, Dana-Maria; Craciun, Anca-ElenaBiomedicines (2022), 10 (2), 308CODEN: BIOMID; ISSN:2227-9059. (MDPI AG)A review. Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its assocns. with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the compn. of gut microbiota, but it is unclear how this, in turn, may influence metab. The main objective of this review is to evaluate the pathogenetic assocn. between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.
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210van Nood, E.; Vrieze, A.; Nieuwdorp, M.; Fuentes, S.; Zoetendal, E. G.; de Vos, W. M.; Visser, C. E.; Kuijper, E. J.; Bartelsman, J. F. W. M.; Tijssen, J. G. P. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. New England Journal of Medicine 2013, 368, 407– 415, DOI: 10.1056/NEJMoa1205037Google Scholar210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXitVelsbs%253D&md5=9e739f9ad764896267b832e89666c9fbDuodenal infusion of donor feces for recurrent clostridium difficilevan Nood, Els; Vrieze, Anne; Nieuwdorp, Max; Fuentes, Susana; Zoetendal, Erwin G.; de Vos, Willem M.; Visser, Caroline E.; Kuijper, Ed J.; Bartelsman, Joep F. W. M.; Tijssen, Jan G. P.; Speelman, Peter; Dijkgraaf, Marcel G. W.; Keller, Josbert J.New England Journal of Medicine (2013), 368 (5), 407-415CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)BACKGROUND Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection. METHODS We randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a soln. of donor feces through a nasoduodenal tube; a std. vancomycin regimen (500 mg orally four times per day for 14 days); or a std. vancomycin regimen with bowel lavage. The primary end point was the resoln. of diarrhea assocd. with C. difficile infection without relapse after 10 wk. RESULTS The study was stopped after an interim anal. Of 16 patients in the infusion group, 13 (81%) had resoln. of C. difficile-assocd. diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resoln. in 2 patients. Resoln. of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were obsd. except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species. CONCLUSIONS The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin.
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211Hamilton, M. J.; Weingarden, A. R.; Sadowsky, M. J.; Khoruts, A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am. J. Gastroenterol. 2012, 107, 761– 767, DOI: 10.1038/ajg.2011.482Google Scholar211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38vhsFOgug%253D%253D&md5=374660d41abfb3c8f52bfb76d82e0606Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infectionHamilton Matthew J; Weingarden Alexa R; Sadowsky Michael J; Khoruts AlexanderThe American journal of gastroenterology (2012), 107 (5), 761-7 ISSN:.OBJECTIVES: While fecal microbiota transplantation (FMT) is historically known to be an effective means to treat recurrent Clostridium difficile infection (CDI) refractory to standard antibiotic therapies, the procedure is rarely performed. At least some of the reasons for limited availability are those of practicality, including aesthetic concerns and costs of donor screening. The objective of this study was to overcome these barriers in our clinical FMT program. METHODS: We report clinical experience with 43 consecutive patients who were treated with FMT for recurrent CDI since inception of this program at the University of Minnesota. During this time, we simplified donor identification and screening by moving from patient-identified individual donors to standard volunteer donors. Material preparation shifted from the endoscopy suite to a standardized process in the laboratory, and ultimately to banking frozen processed fecal material that is ready to use when needed. RESULTS: Standardization of material preparation significantly simplified the practical aspects of FMT without loss of apparent efficacy in clearing recurrent CDI. Approximately 30% of the patients had underlying inflammatory bowel disease, and FMT was equally effective in this group. CONCLUSIONS: Several key steps in the standardization of donor material preparation significantly simplified the clinical practice of FMT for recurrent CDI in patients failing antibiotic therapy.
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212Zafar, H.; Saier, M. H., Jr. Gut Bacteroides species in health and disease. Gut Microbes 2021, 13, 1848158, DOI: 10.1080/19490976.2020.1848158Google ScholarThere is no corresponding record for this reference.
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213Chen, Y.; Yang, Y.; Gu, J. Clinical Implications of the Associations Between Intestinal Microbiome and Colorectal Cancer Progression. Cancer Manag. Res. 2020, 12, 4117– 4128, DOI: 10.2147/CMAR.S240108Google Scholar213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFals7bO&md5=8b18fbdd0f6f9a6d9700a6a4468eededClinical implications of the associations between intestinal microbiome and colorectal cancer progressionChen, Yongkang; Yang, Yong; Gu, JinCancer Management and Research (2020), 12 (), 4117-4128CODEN: CMRACP; ISSN:1179-1322. (Dove Medical Press Ltd.)Intestinal microbiome influences host immunity and several diseases, including cancer, in their areas of colonization. Microbial dysbiosis and over-colonization of specific microbes within the colorectal mucosa can impact the progress of carcinogenesis. Investigations initially focused on the mechanisms by which the intestinal microbiome initiates or promotes the development of colorectal cancer, including DNA damage, induction of chromosomal instability, and regulation of host immune responses. Some studies on the clinicopathol. features have reported that specific strains present at high abundance are assocd. with advanced stage and pos. lymph nodes in colorectal cancer. In this context, we reviewed the relationship between the intestinal microbiome and the clin. features (patient age, disease staging, prognosis, etc.) of patients with colorectal cancer, and evaluated the potential pathogenesis caused by the intestinal microbiome in disease progress. This article assessed whether changes in distinct species or strains occur during the period of cancer advancement. Overall, age grouping does not bring about significant differences in the constitution of microbiome. The disease stages show their distinct distribution in some species and strains. Oncogenic species are generally enriched in patients with poor prognosis, including low infiltration of CD3+ T cells, poor differentiation, widespread invasion, high microsatellite instability, CpG island methylator phenotype, BRAF mutation, short overall survival, and disease-free survival. The implications of those changes we discussed may assist in comprehensive understanding of the tumorigenesis of colorectal cancer from a microbiol. perspective, finding potential biomarkers for colorectal cancer.
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214Bullman, S.; Pedamallu, C. S.; Sicinska, E.; Clancy, T. E.; Zhang, X.; Cai, D.; Neuberg, D.; Huang, K.; Guevara, F.; Nelson, T. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017, 358, 1443– 1448, DOI: 10.1126/science.aal5240Google Scholar214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFGmtrzI&md5=05bc221abb6825e8934c4b24ce4e7b99Analysis of Fusobacterium persistence and antibiotic response in colorectal cancerBullman, Susan; Pedamallu, Chandra S.; Sicinska, Ewa; Clancy, Thomas E.; Zhang, Xiaoyang; Cai, Diana; Neuberg, Donna; Huang, Katherine; Guevara, Fatima; Nelson, Timothy; Chipashvili, Otari; Hagan, Timothy; Walker, Mark; Ramachandran, Aruna; Diosdado, Begona; Serna, Garazi; Mulet, Nuria; Landolfi, Stefania; Ramon y Cajal, Santiago; Fasani, Roberta; Aguirre, Andrew J.; Ng, Kimmie; Elez, Elena; Ogino, Shuji; Tabernero, Josep; Fuchs, Charles S.; Hahn, William C.; Nuciforo, Paolo; Meyerson, MatthewScience (Washington, DC, United States) (2017), 358 (6369), 1443-1448CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Colorectal cancers comprise a complex mixt. of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its assocd. microbiome - including Bacteroides, Selenomonas, and Prevotella species - is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization anal. revealed that Fusobacterium is predominantly assocd. with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its assocd. microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-assocd. colorectal cancer.
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215Cammann, D.; Lu, Y.; Cummings, M. J.; Zhang, M. L.; Cue, J. M.; Do, J.; Ebersole, J.; Chen, X.; Oh, E. C.; Cummings, J. L. Genetic correlations between Alzheimer’s disease and gut microbiome genera. Sci. Rep. 2023, 13, 5258, DOI: 10.1038/s41598-023-31730-5Google Scholar215https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXmvFOisb4%253D&md5=7129ddcd4fb02a9070cb68b6b50d6411Genetic correlations between Alzheimer's disease and gut microbiome generaCammann, Davis; Lu, Yimei; Cummings, Melika J.; Zhang, Mark L.; Cue, Joan Manuel; Do, Jenifer; Ebersole, Jeffrey; Chen, Xiangning; Oh, Edwin C.; Cummings, Jeffrey L.; Chen, JingchunScientific Reports (2023), 13 (1), 5258CODEN: SRCEC3; ISSN:2045-2322. (Nature Portfolio)Abstr.: A growing body of evidence suggests that dysbiosis of the human gut microbiota is assocd. with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide assocn. study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the "best-fit" model implemented in PRSice-2 and detd. the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS anal. in a replication sample (GenADA case/control: 799/778) and then performed a meta-anal. with the PRS results from both samples. Finally, we conducted a linear regression anal. to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically assocd. with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-anal. with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly assocd. with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD assocn. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was pos. correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly assocd. with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.
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216Silva, Y. P.; Bernardi, A.; Frozza, R. L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020, 11, 25, DOI: 10.3389/fendo.2020.00025Google Scholar216https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB387ksFagug%253D%253D&md5=83e69c9f7ec5454ed8e5abfc5bb3ba2bThe Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain CommunicationSilva Ygor Parladore; Frozza Rudimar Luiz; Bernardi AndressaFrontiers in endocrinology (2020), 11 (), 25 ISSN:1664-2392.A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.
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217Manning, L. P.; Yao, C. K.; Biesiekierski, J. R. Therapy of IBS: Is a Low FODMAP Diet the Answer?. Front. Psychiatry 2020, 11, 865, DOI: 10.3389/fpsyt.2020.00865Google Scholar217https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3s7mvVakug%253D%253D&md5=fdc19d32efa4ed24984b261fe4f145daTherapy of IBS: Is a Low FODMAP Diet the Answer?Manning Lauren P; Biesiekierski Jessica R; Yao C KFrontiers in psychiatry (2020), 11 (), 865 ISSN:1664-0640.Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder with a worldwide prevalence of 11%. It is characterized by abdominal pain and altered bowel habits in the absence of underlying unique pathology. The condition is associated with poor quality of life and high use of healthcare resources required for management. The low FODMAP diet (LFD) is a recognized treatment for symptom management of IBS; however, approximately 30% of patients do not respond. The aim of this review was to understand the effectiveness and application of the LFD compared with other dietary and non-dietary interventions. Ten studies were included, eight of which assessed the LFD against other dietary interventions including traditional dietary advice, modified National Institute for Health and Care Excellence guidelines, a high FODMAP diet, gluten-free diet and Mediterranean diet, generalized dietary advice, probiotics, and a sham diet. Two studies compared a LFD to non-diet interventions of gut directed hypnotherapy or yoga. The findings clearly support the LFD as an effective treatment in IBS, and although it highlights the role for microbiota and current psychosocial state, it remains challenging to identify what combination of treatments may be best to ensure a personalized approach and overall higher response rates to IBS therapy.
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218Nanayakkara, W. S.; Skidmore, P. M.; O’Brien, L.; Wilkinson, T. J.; Gearry, R. B. Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date. Clin. Exp. Gastroenterol. 2016, 9, 131– 142, DOI: 10.2147/CEG.S86798Google Scholar218https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmsFWmsbY%253D&md5=33bf40a2ba4a041768f0ab024ef8405bEfficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to dateNanayakkara, Wathsala S.; Skidmore, Paula M. L.; O'Brien, Leigh; Wilkinson, Tim J.; Gearry, Richard B.Clinical and Experimental Gastroenterology (2016), 9 (), 131-142CODEN: CEGLAD; ISSN:1178-7023. (Dove Medical Press Ltd.)This review summarizes the published clin. studies concerning the management of irritable bowel syndrome (IBS) using restriction of Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyols in the diet (low FODMAP diet). In recent years, the data supporting low FODMAP diet for the management of IBS symptoms have emerged, including several randomized controlled trials, case-control studies, and other observational studies. Unlike most dietary manipulations tried in the past to alleviate gastrointestinal symptoms of IBS, all studies on low FODMAP diet have consistently shown symptomatic benefits in the majority of patients with IBS. However, dietary adherence by the patients and clear dietary intervention led by specialized dietitians appear to be vital for the success of the diet. Up to 86% of patients with IBS find improvement in overall gastrointestinal symptoms as well as individual symptoms such as abdominal pain, bloating, constipation, diarrhea, abdominal distention, and flatulence following the diet. FODMAP restriction reduces the osmotic load and gas prodn. in the distal small bowel and the proximal colon, providing symptomatic relief in patients with IBS. Long-term health effects of a low FODMAP diet are not known; however, stringent FODMAP restriction is not recommended owing to risks of inadequate nutrient intake and potential adverse effects from altered gut microbiota. In conclusion, the evidence to date strongly supports the efficacy of a low FODMAP diet in the treatment of IBS. Further studies are required to understand any potential adverse effects of long-term restriction of FODMAPs.
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219Tegegne, B. A.; Kebede, B. Probiotics, their prophylactic and therapeutic applications in human health development: A review of the literature. Heliyon 2022, 8, e09725 DOI: 10.1016/j.heliyon.2022.e09725Google Scholar219https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitFOmurrO&md5=4dbad5bba5cdeba7fe84bb34dba094dfProbiotics, their prophylactic and therapeutic applications in human health development: A review of the literatureTegegne, Bantayehu Addis; Kebede, BekaluHeliyon (2022), 8 (6), e09725CODEN: HELICI; ISSN:2405-8440. (Elsevier Ltd.)Antibiotics do not differentiate between good and bad germs, disrupting normal microflora and causing vitamin deficiency in the human body. They also kill healthy bacteria in the gut and genital tract on a large scale, weakening the host's defense mechanism. Probiotics are a colony of bacteria that live in our intestines and are regarded as a metabolic 'organ' due to their beneficial effects on human health, including metab. and immunol. function. They are used in clin. settings to prevent and treat conditions such as diarrhoea, colon cancer, hypertension, diabetes, acute pancreatitis, Helicobacter pylori infection, ventilator-assocd. pneumonia, migraine and autism. Probiotics may modify immunol. activity by increasing innate and adaptive immune responses, altering microbial habitat in the intestine, improving gut barrier function, competitive adherence to the mucosa and epithelium, and producing antimicrobial compds. The aim of this study is to index that further in depth researches to be conducted on probiotics pivotal role in the prophylaxis and therapeutic usage for a variety of disease that may or may not have treatment alternatives. Key words such as probiotics, microbiota, prophylactics, and therapeutic applications were searched extensively in research databases such as PubMed, PubMed Central (PMC), Scopus, Web of Science, Research Gate, Google Scholar, and Cochrane Library. This concise narrative review article summarized primarily the history, selection, mechanism/mode of action, recent advances in prophylactic and therapeutic applications, and future directions in the use of probiotics for prophylactic and therapeutic applications.
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220Aponte, M.; Murru, N.; Shoukat, M. Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current Perspective. Front. Microbiol. 2020, 11, 562048, DOI: 10.3389/fmicb.2020.562048Google Scholar220https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3s7gtVertg%253D%253D&md5=a2b4712a68074da0900a9a33b293bf93Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current PerspectiveAponte Maria; Shoukat Mahtab; Murru NicolettaFrontiers in microbiology (2020), 11 (), 562048 ISSN:1664-302X.Probiotics are considered as the twenty-first century panpharmacon due to their competent remedial power to cure from gastrointestinal dysbiosis, systematic metabolic diseases, and genetic impairments up to complicated neurodegenerative disorders. They paved the way for an innovative managing of various severe diseases through palatable food products. The probiotics' role as a "bio-therapy" increased their significance in food and medicine due to many competitive advantages over traditional treatment therapies. Their prophylactic and therapeutic potential has been assessed through hundreds of preclinical and clinical studies. In addition, the food industry employs probiotics as functional and nutraceutical ingredients to enhance the added value of food product in terms of increased health benefits. However, regardless of promising health-boosting effects, the probiotics' efficacy still needs an in-depth understanding of systematic mechanisms and factors supporting the healthy actions.
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221Noonan, S.; Zaveri, M.; Macaninch, E.; Martyn, K. Food & mood: a review of supplementary prebiotic and probiotic interventions in the treatment of anxiety and depression in adults. BMJ. Nutrition, Prevention & Health 2020, 3, 351, DOI: 10.1136/bmjnph-2019-000053Google Scholar221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srnsl2ksQ%253D%253D&md5=004737e64c73a75826b75cacfa992c6fFood & mood: a review of supplementary prebiotic and probiotic interventions in the treatment of anxiety and depression in adultsNoonan Sanjay; Zaveri Meena; Macaninch Elaine; Martyn KathyBMJ nutrition, prevention & health (2020), 3 (2), 351-362 ISSN:.BACKGROUND: A bidirectional relationship exists between the brain and the gastrointestinal tract. Foods containing bacteria that positively influence the gastrointestinal microbiome are termed, probiotics; compounds that promote the flourishing of these bacteria are termed, prebiotics. Whether microbiome influencing therapies could treat psychiatric conditions, including depression and anxiety, is an area of interest. Presently, no established consensus for such treatment exists. METHODS: This systematic review analyses databases and grey literature sites to investigate pre and/or probiotics as treatments for depression and/or anxiety disorders. Articles included are from within 15 years. Pre-determined inclusion exclusion criteria were applied, and articles were appraised for their quality using a modified-CASP checklist. This review focuses specifically on quantitative measures from patients with clinical diagnoses of depression and/or anxiety disorders. RESULTS: 7 studies were identified. All demonstrated significant improvements in one or more of the outcomes measuring the of effect taking pre/probiotics compared with no treatment/placebo, or when compared to baseline measurements. DISCUSSION: Our review suggests utilising pre/probiotic may be a potentially useful adjunctive treatment. Furthermore, patients with certain co-morbidities, such as IBS, might experience greater benefits from such treatments, given that pre/probiotic are useful treatments for other conditions that were not the primary focus of this discourse. Our results are limited by several factors: sample sizes (adequate, though not robust); short study durations, long-term effects and propensity for remission undetermined. CONCLUSION: Our results affirm that pre/probiotic therapy warrants further investigation. Efforts should aim to elucidate whether the perceived efficacy of pre/probiotic therapy in depression and/or anxiety disorders can be replicated in larger test populations, and whether such effects are maintained through continued treatment, or post cessation. Interventions should also be investigated in isolation, not combination, to ascertain where the observed effects are attributable to. Efforts to produce mechanistic explanations for such effect should be a priority.
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222MACFARLANE, S.; MACFARLANE, G. T.; CUMMINGS, J. H. Review article: prebiotics in the gastrointestinal tract. Aliment. Pharmacol. Ther. 2006, 24, 701– 714, DOI: 10.1111/j.1365-2036.2006.03042.xGoogle Scholar222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFGqsrvI&md5=326f16c92c2ddf341b9877e55abf9107Review article: prebiotics in the gastrointestinal tractMacFarlane, S.; MacFarlane, G. T.; Cummings, J. H.Alimentary Pharmacology and Therapeutics (2006), 24 (5), 701-714CODEN: APTHEN; ISSN:0269-2813. (Blackwell Publishing Ltd.)A review. Prebiotics are short-chain carbohydrates that alter the compn., or metab., of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, while at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. To review published evidence for prebiotic effects on gut function and human health. We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focusing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clin. study or meta-anal. on this topic. Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus nos. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clin. context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.
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223Dinan, K.; Dinan, T. Antibiotics and mental health: The good, the bad and the ugly. J. Int. Med. 2022, 292, 858– 869, DOI: 10.1111/joim.13543Google Scholar223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MfmvFCmsw%253D%253D&md5=3fcf2535686849b95f568aa4bfe2dbcaAntibiotics and mental health: The good, the bad and the uglyDinan Katherine; Dinan TimothyJournal of internal medicine (2022), 292 (6), 858-869 ISSN:.Antibiotics are recognised as, on occasion, producing psychiatric side effects, most notably depression and anxiety. Apart from antimicrobial activity, antibiotics have multiple off-target effects. The brain-gut-microbiota axis has multiple sites for off-target activity, which may produce either positive or negative antibiotic effects. Here we review how antibiotics impact mental health by acting through the brain-gut-microbiota axis. Microbes in the gut influence brain function by acting through the vagus nerve or by altering the production of short-chain fatty acids or the amino acid tryptophan, the building block of serotonin. Not all antimicrobial actions of antibiotics have a negative impact. The first antidepressant discovered was actually an antibiotic: isoniazid is an antibacterial drug developed for treating tuberculosis. Minocycline, which enters the brain and mediates its effects through microglia, shows antidepressant activity. Some antibiotics bring about a significant decrease in gut microbial diversity, and this is viewed as a risk factor for depression. Other risk factors induced by antibiotics include altered gut barrier function, activation of the hypothalamic-pituitary-adrenal axis, reducing levels of brain-derived neurotrophic factor or oxytocin and alteration of vagal tone. Although most patients taking antibiotics do not suffer from an iatrogenic psychiatric disorder, some do. As clinicians, we need to keep this in mind. The development of new antibiotics is primarily focused on antibiotic resistance, but efforts should be made to reduce off-target brain-gut-microbiota effects resulting in mental health problems.
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224Karakan, T.; Ozkul, C.; Küpeli Akkol, E.; Bilici, S.; Sobarzo-Sánchez, E.; Capasso, R. Gut-Brain-Microbiota Axis: Antibiotics and Functional Gastrointestinal Disorders. Nutrients 2021, 13, 389, DOI: 10.3390/nu13020389Google Scholar224https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXnt1Ggtrc%253D&md5=b62057fce5fb8e10658783a224a8ce59Gut-brain-microbiota axis: antibiotics and functional gastrointestinal disordersKarakan, Tarkan; Ozkul, Ceren; Akkol, Esra Kuepeli; Bilici, Saniye; Sobarzo-Sanchez, Eduardo; Capasso, RaffaeleNutrients (2021), 13 (2), 389CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Gut microbiota compn. and function are major areas of research for functional gastrointestinal disorders. There is a connection between gastrointestinal tract and central nervous system and this is mediated by neurotransmitters, inflammatory cytokines, the vagus nerve and the hypothalamic-pituitary-adrenal axis. Functional gastrointestinal disorders are prevalent diseases affecting more than one third of the population. The etiol. of these disorders is not clarified. Visceral hyperalgesia is the main hypothesis for explaining clin. symptoms, however gut-brain axis disorder is a new terminol. for functional disorders. In this review, microbiota-gut-brain axis connection pathways and related disorders are discussed. Antibiotics are widely used in developed countries and recent evidence indicates antibiotic-induced dysbiosis as an important factor for functional disorders. Antibiotics exert neg. effects on gut microbiota compn. and functions. Antibiotic-induced dysbiosis is a major factor for occurrence of post-infectious irritable bowel syndrome. Cognitive and mood disorders are also frequent in functional gastrointestinal disorders. Animal and human trials show strong evidence for the causal relationship between gut microbiota and brain functions. Therapeutic implications of these newly defined pathogenic pathways are also discussed.
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225Xu, H. M.; Huang, H. L.; Zhou, Y. L.; Zhao, H. L.; Xu, J.; Shou, D. W.; Liu, Y. D.; Zhou, Y. J.; Nie, Y. Q. Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain. Gastroenterol. Res. Pract. 2021, 2021, 6699268, DOI: 10.1155/2021/6699268Google Scholar225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srmslahsQ%253D%253D&md5=6be72c579a7c6003fb60bbe182a0e30eFecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the BrainXu Hao-Ming; Huang Hong-Li; Zhou You-Lian; Zhao Hai-Lan; Xu Jing; Shou Di-Wen; Liu Yan-Di; Zhou Yong-Jian; Nie Yu-QiangGastroenterology research and practice (2021), 2021 (), 6699268 ISSN:1687-6121.Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).
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226Doll, J. P. K.; Vázquez-Castellanos, J. F.; Schaub, A.-C.; Schweinfurth, N.; Kettelhack, C.; Schneider, E.; Yamanbaeva, G.; Mählmann, L.; Brand, S.; Beglinger, C. Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression─Case Report. Front. Psychiatry 2022, 13, 815422, DOI: 10.3389/fpsyt.2022.815422Google Scholar226https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2Mzgt1aitQ%253D%253D&md5=bb6fd052bb3cfe6ba95ac48f9377e2f9Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case ReportDoll Jessica P K; Schaub Anna-Chiara; Schweinfurth Nina; Kettelhack Cedric; Schneider Else; Yamanbaeva Gulnara; Mahlmann Laura; Borgwardt Stefan; Schmidt Andre; Lang Undine E; Vazquez-Castellanos Jorge F; Raes Jeroen; Brand Serge; Brand Serge; Brand Serge; Brand Serge; Brand Serge; Beglinger Christoph; Borgwardt StefanFrontiers in psychiatry (2022), 13 (), 815422 ISSN:1664-0640.Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment.
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227Waller, K. M. J.; Leong, R. W.; Paramsothy, S. An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases. J. Gastroenterol. Hepatol. 2022, 37, 246– 255, DOI: 10.1111/jgh.15731Google Scholar227https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cjoslyisQ%253D%253D&md5=f99ac67810d7f66adee95e075d5ce2a4An update on fecal microbiota transplantation for the treatment of gastrointestinal diseasesWaller Karen M J; Leong Rupert W; Paramsothy Sudarshan; Waller Karen M J; Leong Rupert W; Paramsothy Sudarshan; Leong Rupert W; Paramsothy SudarshanJournal of gastroenterology and hepatology (2022), 37 (2), 246-255 ISSN:.Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.
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228Hetterich, L.; Stengel, A. Psychotherapeutic Interventions in Irritable Bowel Syndrome. Front. Psychiatry 2020, 11, 286, DOI: 10.3389/fpsyt.2020.00286Google Scholar228https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38voslWisg%253D%253D&md5=eda0cab2d8bca2378779a256d71f2cd1Psychotherapeutic Interventions in Irritable Bowel SyndromeHetterich Larissa; Stengel Andreas; Stengel AndreasFrontiers in psychiatry (2020), 11 (), 286 ISSN:1664-0640.Irritable bowel syndrome (IBS) is a frequent functional gastrointestinal disorder. The patients complain about various symptoms like change in bowel habits, constipation or diarrhea, abdominal pain, and meteorism leading to a great reduction in quality of life. The pathophysiology is complex and best explained using the biopsychosocial model encompassing biological, psychological as well as (psycho)social factors. In line with the multitude of underlying factors, the treatment is comprised of a multitude of components. Often, patients start with lifestyle changes and dietary advice followed by medical treatment. However, also psychotherapy is an important treatment option for patients with IBS and should not be restricted to those with psychiatric comorbidities. Several evidence-based psychotherapeutic treatment options exist such as psychoeducation, self-help, cognitive behavioral therapy, psychodynamic psychotherapy, hypnotherapy, mindfulness-based therapy, and relaxation therapy which will be discussed in the present review.
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229Wildes, J. E.; Bedell, A.; Graham, A. K.; Kells, M. Brain-gut psychotherapies: Promising tools to address gastrointestinal problems in patients with eating disorders. Int. J. Eat. Disord. 2021, 54, 1063– 1067, DOI: 10.1002/eat.23555Google Scholar229https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c%252FmvVCqsQ%253D%253D&md5=c1bc34b65c12c712ec05ad55fcac0d4eBrain-gut psychotherapies: Promising tools to address gastrointestinal problems in patients with eating disordersWildes Jennifer E; Bedell Alyse; Kells Meredith; Graham Andrea K; Graham Andrea KThe International journal of eating disorders (2021), 54 (6), 1063-1067 ISSN:.Gastrointestinal (GI) problems are common in individuals with eating disorders (EDs) and associated with distress, impairment, and increased healthcare utilization. GI symptoms may be exacerbated by meals and other interventions central to ED recovery thereby contributing to negative clinical outcomes. Informed by models emphasizing the role of the brain-gut axis in the expression of GI symptoms, this article describes a program of research to adapt "brain-gut psychotherapies" for EDs. First, the role of the brain-gut axis in GI symptoms is described, and evidence-based brain-gut psychotherapies are reviewed, with an emphasis on cognitive behavioral therapy for GI disorders and gut-directed hypnotherapy. Next, future directions for research in EDs to (a) understand the impact of GI symptoms on illness course and outcome; (b) clarify target engagement; (c) evaluate brain-gut psychotherapies; and (d) optimize intervention reach and delivery are described. We present a conceptual model that emphasizes GI-specific anxiety and altered gut physiology as targets of brain-gut psychotherapies in EDs, and discuss several issues that need to be addressed in designing clinical trials to test these interventions. We also describe how engagement with multidisciplinary stakeholders and use of digital tools could speed translation from the laboratory to clinical settings.
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230Laird, K. T.; Tanner-Smith, E. E.; Russell, A. C.; Hollon, S. D.; Walker, L. S. Comparative efficacy of psychological therapies for improving mental health and daily functioning in irritable bowel syndrome: A systematic review and meta-analysis. Clin. Psychol. Rev. 2017, 51, 142– 152, DOI: 10.1016/j.cpr.2016.11.001Google Scholar230https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2snoslykuw%253D%253D&md5=de6427a342c2a2a66e5d5a248aa4db29Comparative efficacy of psychological therapies for improving mental health and daily functioning in irritable bowel syndrome: A systematic review and meta-analysisLaird Kelsey T; Tanner-Smith Emily E; Russell Alexandra C; Walker Lynn S; Hollon Steven DClinical psychology review (2017), 51 (), 142-152 ISSN:.Previous meta-analyses have shown that psychotherapy improves gastrointestinal symptoms in adults with irritable bowel syndrome (IBS); however, the impact on functioning in daily activities is unknown. Meta-analysis was used to estimate the effect of psychotherapy on mental health and daily functioning in adults with IBS. An extensive literature search located 28 eligible randomized controlled trials (RCTs) providing outcome data for mental health and 18 RCTs providing data for daily functioning. Compared to a mixed group of control conditions, psychotherapy produced significantly greater improvements to mental health (d-=0.41) and daily functioning (d-=0.43). Cognitive behavior therapy (CBT) was evaluated in the largest number of trials (21 trials), followed by hypnosis (4 trials), psychodynamic (3 trials), and relaxation (2 trials). The psychotherapeutic modalities were comparable with respect to their effect on mental health. CBT produced the greatest improvements to daily functioning, and this effect was significantly larger than that produced by relaxation therapy. These results have important clinical implications for treatment of adults with IBS.
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231Colomier, E.; Algera, J.; Melchior, C. Pharmacological Therapies and Their Clinical Targets in Irritable Bowel Syndrome With Diarrhea. Front. Pharmacol. 2021, 11, 629026, DOI: 10.3389/fphar.2020.629026Google ScholarThere is no corresponding record for this reference.
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232World Health Organization. Pharmacological treatment of mental disorders in primary health care. WHO Press: Geneva, Switzerland, 2009.Google ScholarThere is no corresponding record for this reference.
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233Fikree, A.; Byrne, P. Management of functional gastrointestinal disorders. Clin Med. (Lond) 2021, 21, 44– 52, DOI: 10.7861/clinmed.2020-0980Google Scholar233https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srjsFKhtQ%253D%253D&md5=6507a255122bb692c704d190651a1e1fManagement of functional gastrointestinal disordersFikree Asma; Byrne PeterClinical medicine (London, England) (2021), 21 (1), 44-52 ISSN:.Functional gastrointestinal (GI) disorders (eg irritable bowel syndrome and functional dyspepsia) are very common conditions which are associated with very poor quality of life and high healthcare utilisation. They are caused by disorders of GI functioning, namely altered gut sensitivity, motility, microbiota, immune functioning and central nervous system processing. They cause chronic symptoms throughout the gut (eg pain, dyspepsia and altered bowel habit), all of which are made worse by maladaptive patient behaviours, stress and psychological comorbidity. Management involves a biopsychosocial approach involving changes in lifestyle and diet, addressing coexisting psychological comorbidity and using medication to treat underlying pathophysiology. Pharmacological treatment with antispasmodics, neuromodulators, motility agents and antidepressants is effective. Psychotherapy in motivated individuals is equally effective. Success of treatment is increased by a good doctor-patient relationship and so this needs to be taken into account during the consultation.
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234Tierney, B. T.; Yang, Z.; Luber, J. M.; Beaudin, M.; Wibowo, M. C.; Baek, C.; Mehlenbacher, E.; Patel, C. J.; Kostic, A. D. The Landscape of Genetic Content in the Gut and Oral Human Microbiome. Cell Host Microbe 2019, 26, 283– 295.e288, DOI: 10.1016/j.chom.2019.07.008Google Scholar234https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1Sit7zL&md5=add2f2ab5cb4b28803e5e50f0192a132The Landscape of Genetic Content in the Gut and Oral Human MicrobiomeTierney, Braden T.; Yang, Zhen; Luber, Jacob M.; Beaudin, Marc; Wibowo, Marsha C.; Baek, Christina; Mehlenbacher, Eleanor; Patel, Chirag J.; Kostic, Aleksandar D.Cell Host & Microbe (2019), 26 (2), 283-295.e8CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)Meta-anal. of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were "singletons," or unique to a single metagenomic sample. Singletons were enriched for different functions (compared with non-singletons) and arose from sub-population-specific microbial strains. Overall, these results provide potential bases for the unexplained heterogeneity obsd. in microbiome-derived human phenotypes.
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235International Human Genome Sequencing Consortium Finishing the euchromatic sequence of the human genome. Nature 2004, 431, 931– 945, DOI: 10.1038/nature03001Google ScholarThere is no corresponding record for this reference.
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236Liu, J.; Tan, Y.; Cheng, H.; Zhang, D.; Feng, W.; Peng, C. Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives. Aging Dis. 2022, 13, 1106– 1126, DOI: 10.14336/AD.2022.0104Google Scholar236https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MbgsFGktg%253D%253D&md5=e5d73d8cf72eb8a31636780eb1a15a27Functions of Gut Microbiota Metabolites, Current Status and Future PerspectivesLiu Juan; Tan Yuzhu; Cheng Hao; Zhang Dandan; Feng Wuwen; Peng Cheng; Cheng Hao; Zhang Dandan; Feng Wuwen; Peng ChengAging and disease (2022), 13 (4), 1106-1126 ISSN:2152-5250.Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health.
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237Heijtz, R. D.; Wang, S.; Anuar, F.; Qian, Y.; Björkholm, B.; Samuelsson, A.; Hibberd, M. L.; Forssberg, H.; Pettersson, S. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 3047– 3052, DOI: 10.1073/pnas.1010529108Google Scholar237https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXisVans7k%253D&md5=120bcfa2cddbab592375dd2e671cf069Normal gut microbiota modulates brain development and behaviorHeijtz, Rochellys Diaz; Wang, Shugui; Anuar, Farhana; Qian, Yu; Bjorkholm, Britta; Samuelsson, Annika; Hibberd, Martin L.; Forssberg, Hans; Pettersson, SvenProceedings of the National Academy of Sciences of the United States of America (2011), 108 (7), 3047-3052, S3047/1-S3047/5CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Microbial colonization of mammals is an evolution-driven process that modulate host physiol., many of which are assocd. with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is assocd. with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
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238Sudo, N.; Chida, Y.; Aiba, Y.; Sonoda, J.; Oyama, N.; Yu, X.-N.; Kubo, C.; Koga, Y. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. Journal of Physiology 2004, 558, 263– 275, DOI: 10.1113/jphysiol.2004.063388Google Scholar238https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtFWhtro%253D&md5=eed1b25785166e5444218089f6abe1fePostnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in miceSudo, Nobuyuki; Chida, Yoichi; Aiba, Yuji; Sonoda, Junko; Oyama, Naomi; Yu, Xiao-Nian; Kubo, Chiharu; Koga, YasuhiroJournal of Physiology (Oxford, United Kingdom) (2004), 558 (1), 263-275CODEN: JPHYA7; ISSN:0022-3751. (Blackwell Publishing Ltd.)Indigenous microbiota have several beneficial effects on host physiol. functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiol. system response. To test the idea that such microbes may affect the development of neural systems that govern the endocrine response to stress, we investigated hypothalamic-pituitary-adrenal (HPA) reaction to stress by comparing germ-free (GF), specific pathogen free (SPF) and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not in response to stimulation with ether. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassocn. with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced the response to stress. Importantly, the enhanced HPA response of GF mice was partly cor. by reconstitution with SPF feces at an early stage, but not by any reconstitution exerted at a later stage, which therefore indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of the HPA stress response in mice.
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239Needham, B. D.; Funabashi, M.; Adame, M. D.; Wang, Z.; Boktor, J. C.; Haney, J.; Wu, W.-L.; Rabut, C.; Ladinsky, M. S.; Hwang, S.-J. A gut-derived metabolite alters brain activity and anxiety behaviour in mice. Nature 2022, 602, 647– 653, DOI: 10.1038/s41586-022-04396-8Google Scholar239https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xjs12kurk%253D&md5=3bf0205ec8a2eeef83f05239deedbfddA gut-derived metabolite alters brain activity and anxiety behaviour in miceNeedham, Brittany D.; Funabashi, Masanori; Adame, Mark D.; Wang, Zhuo; Boktor, Joseph C.; Haney, Jillian; Wu, Wei-Li; Rabut, Claire; Ladinsky, Mark S.; Hwang, Son-Jong; Guo, Yumei; Zhu, Qiyun; Griffiths, Jessica A.; Knight, Rob; Bjorkman, Pamela J.; Shapiro, Mikhail G.; Geschwind, Daniel H.; Holschneider, Daniel P.; Fischbach, Michael A.; Mazmanian, Sarkis K.Nature (London, United Kingdom) (2022), 602 (7898), 647-653CODEN: NATUAS; ISSN:1476-4687. (Nature Portfolio)Integration of sensory and mol. inputs from the environment shapes animal behavior. A major site of exposure to environmental mols. is the gastrointestinal tract, in which dietary components are chem. transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behavior3, modulates neurotransmitter prodn. in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was assocd. with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been assocd. with behavioral outcomes7,9-14. Accordingly, we obsd. that mice exposed to 4EPS displayed anxiety-like behaviors, and pharmacol. treatments that promote oligodendrocyte differentiation prevented the behavioral effects of 4EPS. These findings reveal that a gut-derived mol. influences complex behaviors in mice through effects on oligodendrocyte function and myelin patterning in the brain.
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240Gacias, M.; Gaspari, S.; Santos, P.-M. G.; Tamburini, S.; Andrade, M.; Zhang, F.; Shen, N.; Tolstikov, V.; Kiebish, M. A.; Dupree, J. L. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. eLife 2016, 5, e13442, DOI: 10.7554/eLife.13442Google Scholar240https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtlGmsL8%253D&md5=ba6cf36afd24925d0ac0af6a370c1632Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behaviourGacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae; Tamburini, Sabrina; Andrade, Monica; Zhang, Fan; Shen, Nan; Tolstikov, Vladimir; Kiebish, Michael A.; Dupree, Jeffrey L.; Zachariou, Venetia; Clemente, Jose C.; Casaccia, PatriziaeLife (2016), 5 (), e13442/1-e13442/27CODEN: ELIFA8; ISSN:2050-084X. (eLife Sciences Publications Ltd.)Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not obsd. in C57BL/6 mice. This was not obsd. in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic anal. identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.
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241Vuong, H. E.; Pronovost, G. N.; Williams, D. W.; Coley, E. J. L.; Siegler, E. L.; Qiu, A.; Kazantsev, M.; Wilson, C. J.; Rendon, T.; Hsiao, E. Y. The maternal microbiome modulates fetal neurodevelopment in mice. Nature 2020, 586, 281– 286, DOI: 10.1038/s41586-020-2745-3Google Scholar241https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFWmurvO&md5=41f2ee099d320a2359f5d5e194bda294The maternal microbiome modulates fetal neurodevelopment in miceVuong, Helen E.; Pronovost, Geoffrey N.; Williams, Drake W.; Coley, Elena J. L.; Siegler, Emily L.; Qiu, Austin; Kazantsev, Maria; Wilson, Chantel J.; Rendon, Tomiko; Hsiao, Elaine Y.Nature (London, United Kingdom) (2020), 586 (7828), 281-286CODEN: NATUAS; ISSN:0028-0836. (Nature Research)'Dysbiosis' of the maternal gut microbiome, in response to challenges such as infection1, altered diet2 and stress3 during pregnancy, has been increasingly assocd. with abnormalities in brain function and behavior of the offspring4. However, it is unclear whether the maternal gut microbiome influences neurodevelopment during crit. prenatal periods and in the absence of environmental challenges. Here we investigate how depletion and selective reconstitution of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibited reduced brain expression of genes related to axonogenesis, deficient thalamocortical axons and impaired outgrowth of thalamic axons in response to cell-extrinsic factors. Gnotobiotic colonization of microbiome-depleted dams with a limited consortium of bacteria prevented abnormalities in fetal brain gene expression and thalamocortical axonogenesis. Metabolomic profiling revealed that the maternal microbiome regulates numerous small mols. in the maternal serum and the brains of fetal offspring. Select microbiota-dependent metabolites promoted axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with these metabolites abrogated deficiencies in fetal thalamocortical axons. Manipulation of the maternal microbiome and microbial metabolites during pregnancy yielded adult offspring with altered tactile sensitivity in two aversive somatosensory behavioral tasks, but no overt differences in many other sensorimotor behaviors. Together, our findings show that the maternal gut microbiome promotes fetal thalamocortical axonogenesis, probably through signalling by microbially modulated metabolites to neurons in the developing brain.
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242Wei, G. Z.; Martin, K. A.; Xing, P. Y.; Agrawal, R.; Whiley, L.; Wood, T. K.; Hejndorf, S.; Ng, Y. Z.; Low, J. Z. Y.; Rossant, J. Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor. Proc. Natl. Acad. Sci. U. S. A. 2021, 118, e2021091118, DOI: 10.1073/pnas.2021091118Google Scholar242https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsFSns7bM&md5=6a699c1abd8c4de300b6ec4a4d8ebff9Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptorWei, George Zhang; Martin, Katherine A.; Xing, Peter Yuli; Agrawal, Ruchi; Whiley, Luke; Wood, Thomas K.; Hejndorf, Sophia; Ng, Yong Zhi; Yan Low, Jeremy Zhi; Rossant, Janet; Nechanitzky, Robert; Holmes, Elaine; Nicholson, Jeremy K.; Tan, Eng-King; Matthews, Paul M.; Pettersson, SvenProceedings of the National Academy of Sciences of the United States of America (2021), 118 (27), e2021091118CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)While modulatory effects of gut microbes on neurol. phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic d. protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not obsd. with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a mol. pathway connecting gut microbiota compn. and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.
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243Kang, D.-W.; Adams, J. B.; Gregory, A. C.; Borody, T.; Chittick, L.; Fasano, A.; Khoruts, A.; Geis, E.; Maldonado, J.; McDonough-Means, S. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 2017, 5, 10, DOI: 10.1186/s40168-016-0225-7Google Scholar243https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1c7pt1Gksw%253D%253D&md5=9c81c841550249c4ef4b2c5ccc9e52caMicrobiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label studyKang Dae-Wook; Maldonado Juan; Krajmalnik-Brown Rosa; Adams James B; Geis Elizabeth; Pollard Elena L; Gregory Ann C; Sullivan Matthew B; Gregory Ann C; Chittick Lauren; Roux Simon; Sullivan Matthew B; Borody Thomas; Chittick Lauren; Roux Simon; Sullivan Matthew B; Fasano Alessio; Khoruts Alexander; Khoruts Alexander; Sadowsky Michael J; Khoruts Alexander; McDonough-Means Sharon; Sadowsky Michael J; Lipson Karen Schwarzberg; Caporaso J Gregory; Sullivan Matthew B; Caporaso J Gregory; Krajmalnik-Brown RosaMicrobiome (2017), 5 (1), 10 ISSN:.BACKGROUND: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10(13) bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. RESULTS: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). CONCLUSIONS: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. TRIAL REGISTRATION: This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
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244Korpela, K.; Helve, O.; Kolho, K. L.; Saisto, T.; Skogberg, K.; Dikareva, E.; Stefanovic, V.; Salonen, A.; Andersson, S.; de Vos, W. M. Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study. Cell 2020, 183, 324– 334.e325, DOI: 10.1016/j.cell.2020.08.047Google Scholar244https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFyqt7%252FP&md5=8cf28050f83c4ecf2c922f3f744ee098Maternal Fecal Microbiota Transplantation in Cesarean-born infants rapidly restores normal Gut Microbial Development: A Proof-of-Concept StudyKorpela, Katri; Helve, Otto; Kolho, Kaija-Leena; Saisto, Terhi; Skogberg, Kirsi; Dikareva, Evgenia; Stefanovic, Vedran; Salonen, Anne; Andersson, Sture; de Vos, Willem M.Cell (Cambridge, MA, United States) (2020), 183 (2), 324-334.e5CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a dild. fecal sample from their own mothers, taken 3 wk prior to delivery. All seven infants had an uneventful clin. course during the 3-mo follow-up and showed no adverse effects. The temporal development of the fecal microbiota compn. of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clin. and microbiol. screening.
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245Wikoff, W. R.; Anfora, A. T.; Liu, J.; Schultz, P. G.; Lesley, S. A.; Peters, E. C.; Siuzdak, G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 3698– 3703, DOI: 10.1073/pnas.0812874106Google Scholar245https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjt1Gksrk%253D&md5=2056708fdbccc79f1fa28b5ecfdc694eMetabolomics analysis reveals large effects of gut microflora on mammalian blood metabolitesWikoff, William R.; Anfora, Andrew T.; Liu, Jun; Schultz, Peter G.; Lesley, Scott A.; Peters, Eric C.; Siuzdak, GaryProceedings of the National Academy of Sciences of the United States of America (2009), 106 (10), 3698-3703CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Although it has long been recognized that the enteric community of bacteria that inhabit the human distal intestinal track broadly impacts human health, the biochem. details that underlie these effects remain largely undefined. Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut "microbiome" on mammalian blood metabolites. Plasma exts. from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas ≈10% of all features obsd. in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. For example, the bacterial-mediated prodn. of bioactive indole-contg. metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Prodn. of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. Multiple org. acids contg. Ph groups were also greatly increased in the presence of gut microbes. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was obsd., suggesting that the gut microflora has a direct impact on the drug metab. capacity of the host. Together, these results suggest a significant interplay between bacterial and mammalian metab.
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246Dodd, D.; Spitzer, M. H.; Van Treuren, W.; Merrill, B. D.; Hryckowian, A. J.; Higginbottom, S. K.; Le, A.; Cowan, T. M.; Nolan, G. P.; Fischbach, M. A. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 2017, 551, 648– 652, DOI: 10.1038/nature24661Google Scholar246https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvVynsLnJ&md5=df143bcb59e17bb7cc33dffbd843689eA gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolitesDodd, Dylan; Spitzer, Matthew H.; Van Treuren, William; Merrill, Bryan D.; Hryckowian, Andrew J.; Higginbottom, Steven K.; Le, Anthony; Cowan, Tina M.; Nolan, Garry P.; Fischbach, Michael A.; Sonnenburg, Justin L.Nature (London, United Kingdom) (2017), 551 (7682), 648-652CODEN: NATUAS; ISSN:0028-0836. (Nature Research)The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small mols. commonly reach concns. similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates arom. amino acid metabolites. Our results reveal that this pathway produces twelve compds., nine of which are known to accumulate in host serum. All three arom. amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the mol. output of the gut bacterial community.
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247Barrett, E.; Ross, R. P.; O’Toole, P. W.; Fitzgerald, G. F.; Stanton, C. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 2012, 113, 411– 417, DOI: 10.1111/j.1365-2672.2012.05344.xGoogle Scholar247https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFCktbvF&md5=dcf88e5c216766fbe060d473078d696eγ-Aminobutyric acid production by culturable bacteria from the human intestineBarrett, E.; Ross, R. P.; O'Toole, P. W.; Fitzgerald, G. F.; Stanton, C.Journal of Applied Microbiology (2012), 113 (2), 411-417CODEN: JAMIFK; ISSN:1364-5072. (Wiley-Blackwell)The aim was to assess the ability of human intestinally derived strains of Lactobacillus and Bifidobacterium to produce γ-aminobutyric acid (GABA). Strains of Lactobacillus and Bifidobacterium were grown in medium contg. monosodium glutamate (MSG). Growth of the bacteria and conversion of MSG to GABA were measured. Of 91 intestinally derived bacteria assessed, one Lactobacillus strain and four strains of Bifidobacterium produced GABA. Lactobacillus brevisDPC6108 was the most efficient of the strains tested, converting up to 100% of MSG to GABA. The ability of the cultured intestinal strains to produce GABA was investigated using a simple pH-controlled anaerobic faeces-based fermn., supplemented with 30 mg ml-1 MSG. The addn. of Lact. brevisDPC6108 to a faeces-based fermn. significantly increased the GABA concn. (P < 0·001), supporting the notion that this biosynthesis could occur in vivo. The prodn. of GABA by bifidobacteria exhibited considerable interspecies variation. Lactobacillus brevis and Bifidobacterium dentium were the most efficient GABA producers among the range of strains tested. The addn. of Lact. brevisDPC6108 to the culturable gut microbiota increased the GABA concn. in fermented faecal slurry at physiol. pH. Identification of optimal MSG conversion to GABA by particular cultured elements of the commensal intestinal microbiota and the demonstration that this can occur under simulated in vivo conditions offer new prospects for microbiota modulation to promote health.
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248Asano, Y.; Hiramoto, T.; Nishino, R.; Aiba, Y.; Kimura, T.; Yoshihara, K.; Koga, Y.; Sudo, N. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303, G1288– 1295, DOI: 10.1152/ajpgi.00341.2012Google ScholarThere is no corresponding record for this reference.
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249Pocivavsek, A.; Wu, H.-Q.; Potter, M. C.; Elmer, G. I.; Pellicciari, R.; Schwarcz, R. Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory. Neuropsychopharmacology 2011, 36, 2357– 2367, DOI: 10.1038/npp.2011.127Google Scholar249https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFyms7bN&md5=68f97aa462679aadd3af5b5eb106e084Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and MemoryPocivavsek, Ana; Wu, Hui-Qiu; Potter, Michelle C.; Elmer, Greg I.; Pellicciari, Roberto; Schwarcz, RobertNeuropsychopharmacology (2011), 36 (11), 2357-2367CODEN: NEROEW; ISSN:0893-133X. (Nature Publishing Group)Kynurenic acid (KYNA), an astrocyte-derived metabolite, antagonizes the α7 nicotinic acetylcholine receptor (α7nAChR) and, possibly, the glycine co-agonist site of the NMDA receptor at endogenous brain concns. As both receptors are involved in cognitive processes, KYNA elevations may aggravate, whereas redns. may improve, cognitive functions. We tested this hypothesis in rats by examg. the effects of acute up- or downregulation of endogenous KYNA on extracellular glutamate in the hippocampus and on performance in the Morris water maze (MWM). Applied directly by reverse dialysis, KYNA (30-300 nM) reduced, whereas the specific kynurenine aminotransferase-II inhibitor (S)-4-(ethylsulfonyl)benzoylalanine (ESBA; 0.3-3 mM) raised, extracellular glutamate levels in the hippocampus. Co-application of KYNA (100 nM) with ESBA (1 mM) prevented the ESBA-induced glutamate increase. Comparable effects on hippocampal glutamate levels were seen after intra-cerebroventricular (i.c.v.) application of the KYNA precursor kynurenine (1 mM, 10 μl) or ESBA (10 mM, 10 μl), resp. In sep. animals, i.c.v. treatment with kynurenine impaired, whereas i.c.v. ESBA improved, performance in the MWM. I.c.v. co-application of KYNA (10 μM) eliminated the pro-cognitive effects of ESBA. Collectively, these studies show that KYNA serves as an endogenous modulator of extracellular glutamate in the hippocampus and regulates hippocampus-related cognitive function. Our results suggest that pharmacol. interventions leading to acute redns. in hippocampal KYNA constitute an effective strategy for cognitive improvement. This approach might be esp. useful in the treatment of cognitive deficits in neurol. and psychiatric diseases that are assocd. with increased brain KYNA levels. Neuropsychopharmacol. (2011) 36, 2357-2367; doi:10.1038/npp.2011.127; published online 27 July 2011.
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250Potter, M. C.; Elmer, G. I.; Bergeron, R.; Albuquerque, E. X.; Guidetti, P.; Wu, H.-Q.; Schwarcz, R. Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive Behavior. Neuropsychopharmacology 2010, 35, 1734– 1742, DOI: 10.1038/npp.2010.39Google Scholar250https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnsVOnsbY%253D&md5=3f26ceee98561f8a40d694645f16f2f9Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive BehaviorPotter, Michelle C.; Elmer, Greg I.; Bergeron, Richard; Albuquerque, Edson X.; Guidetti, Paolo; Wu, Hui-Qiu; Schwarcz, RobertNeuropsychopharmacology (2010), 35 (8), 1734-1742CODEN: NEROEW; ISSN:0893-133X. (Nature Publishing Group)At endogenous brain concns., the astrocyte-derived metabolite kynurenic acid (KYNA) antagonizes the α7 nicotinic acetylcholine receptor and, possibly, the glycine co-agonist site of the NMDA receptor. The functions of these two receptors, which are intimately involved in synaptic plasticity and cognitive processes, may, therefore, be enhanced by redns. in brain KYNA levels. This concept was tested in mice with a targeted deletion of kynurenine aminotransferase II (KAT II), a major biosynthetic enzyme of brain KYNA. At 21 days of age, KAT II knock-out mice had reduced hippocampal KYNA levels (-71%) and showed significantly increased performance in three cognitive paradigms that rely in part on the integrity of hippocampal function, namely object exploration and recognition, passive avoidance, and spatial discrimination. Moreover, compared with wild-type controls, hippocampal slices from KAT II-deficient mice showed a significant increase in the amplitude of long-term potentiation in vitro. These functional changes were accompanied by reduced extracellular KYNA (-66%) and increased extracellular glutamate (+51%) concns., measured by hippocampal microdialysis in vivo. Taken together, a picture emerges in which a redn. in the astrocytic formation of KYNA increases glutamatergic tone in the hippocampus and enhances cognitive abilities and synaptic plasticity. Our studies raise the prospect that interventions aimed specifically at reducing KYNA formation in the brain may constitute a promising mol. strategy for cognitive improvement in health and disease.
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251Reigstad, C. S.; Salmonson, C. E.; Rainey, J. F., III; Szurszewski, J. H.; Linden, D. R.; Sonnenburg, J. L.; Farrugia, G.; Kashyap, P. C. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2015, 29, 1395– 1403, DOI: 10.1096/fj.14-259598Google Scholar251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmsFahsr4%253D&md5=e94fb047d3a97dc2f4ee14acf6ef9877Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cellsReigstad, Christopher S.; Salmonson, Charles E.; Rainey, John F., III; Szurszewski, Joseph H.; Linden, David R.; Sonnenburg, Justin L.; Farrugia, Gianrico; Kashyap, Purna C.FASEB Journal (2015), 29 (4), 1395-1403CODEN: FAJOEC; ISSN:0892-6638. (Federation of American Societies for Experimental Biology)Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To det. the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P < 0.01] and chromogranin A (neuroendocrine secretion; P < 0.01), with no effect on monoamine oxidase A (serotonin catabolism), serotonin receptor 5-HT4, or mouse serotonin transporter. HM and CR mice also had increased colonic Tph1 protein (P < 0.05) and 5-HT concns. (GF, 17 ± 3 ng/mg; HM, 25 ± 2 ng/mg; and CR, 35 ± 3 ng/mg; P < 0.05). Enterochromaffin (EC) cell nos. (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT prodn. and homeostasis.
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252Yano, J. M.; Yu, K.; Donaldson, G. P.; Shastri, G. G.; Ann, P.; Ma, L.; Nagler, C. R.; Ismagilov, R. F.; Mazmanian, S. K.; Hsiao, E. Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015, 161, 264– 276, DOI: 10.1016/j.cell.2015.02.047Google Scholar252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmsVWqsLk%253D&md5=5c9ef92794dedb7b9fe60b5d4b825a46Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin BiosynthesisYano, Jessica M.; Yu, Kristie; Donaldson, Gregory P.; Shastri, Gauri G.; Ann, Phoebe; Ma, Liang; Nagler, Cathryn R.; Ismagilov, Rustem F.; Mazmanian, Sarkis K.; Hsiao, Elaine Y.Cell (Cambridge, MA, United States) (2015), 161 (2), 264-276CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metab. of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a crit. role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiol., modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concns. of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biol. processes.
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253Bellono, N. W.; Bayrer, J. R.; Leitch, D. B.; Castro, J.; Zhang, C.; O’Donnell, T. A.; Brierley, S. M.; Ingraham, H. A.; Julius, D. Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell 2017, 170, 185– 198.e16, DOI: 10.1016/j.cell.2017.05.034Google Scholar253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVOjtr7F&md5=88668aed566a2bfb515067b7dcda5789Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural PathwaysBellono, Nicholas W.; Bayrer, James R.; Leitch, Duncan B.; Castro, Joel; Zhang, Chuchu; O'Donnell, Tracey A.; Brierley, Stuart M.; Ingraham, Holly A.; Julius, DavidCell (Cambridge, MA, United States) (2017), 170 (1), 185-198.e16CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiol. processes ranging from metab. to cognition. The gut epithelium is a principal site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single-cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single-cell measurements to elucidate intrinsic biophys., pharmacol., and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are elec. excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.
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254Ye, L.; Bae, M.; Cassilly, C. D.; Jabba, S. V.; Thorpe, D. W.; Martin, A. M.; Lu, H. Y.; Wang, J.; Thompson, J. D.; Lickwar, C. R. Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways. Cell Host Microbe 2021, 29, 179– 196.e79, DOI: 10.1016/j.chom.2020.11.011Google Scholar254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXktlajsw%253D%253D&md5=4abd750d5836a0e6f1b530180778294fEnteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathwaysYe, Lihua; Bae, Munhyung; Cassilly, Chelsi D.; Jabba, Sairam V.; Thorpe, Daniel W.; Martin, Alyce M.; Lu, Hsiu-Yi; Wang, Jinhu; Thompson, John D.; Lickwar, Colin R.; Poss, Kenneth D.; Keating, Damien J.; Jordt, Sven-Eric; Clardy, Jon; Liddle, Rodger A.; Rawls, John F.Cell Host & Microbe (2021), 29 (2), 179-196.e9CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility. Microbial, pharmacol., or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons by secreting the neurotransmitter 5-hydroxytryptamine (5-HT). A subset of indole derivs. of tryptophan catabolism produced by E. tarda and other gut microbes activates zebrafish EEC Trpa1 signaling. These catabolites also directly stimulate human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a mol. pathway by which EECs regulate enteric and vagal neuronal pathways in response to microbial signals.
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255O’Hagan, C.; Li, J. V.; Marchesi, J. R.; Plummer, S.; Garaiova, I.; Good, M. A. Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats. Neurobiol Learn Mem 2017, 144, 36– 47, DOI: 10.1016/j.nlm.2017.05.015Google Scholar255https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVGktr3J&md5=4ea879e2715e8e481dff3b0b7e02fa3eLong-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged ratsO'Hagan, Caroline; Li, Jia V.; Marchesi, Julian R.; Plummer, Sue; Garaiova, Iveta; Good, Mark A.Neurobiology of Learning and Memory (2017), 144 (), 36-47CODEN: NLMEFR; ISSN:1074-7427. (Elsevier Inc.)Ageing is assocd. with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and prodn. of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixt. (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioral flexibility in 15-17-mo-old male rats. Following behavioral testing, the hippocampus and prefrontal cortex was extd. and analyzed ex vivo using 1H NMR (1H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place assocns. Short-term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. 1H NMR anal. revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory.
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256Mao, J.-H.; Kim, Y.-M.; Zhou, Y.-X.; Hu, D.; Zhong, C.; Chang, H.; Brislawn, C. J.; Fansler, S.; Langley, S.; Wang, Y. Genetic and metabolic links between the murine microbiome and memory. Microbiome 2020, 8, 53, DOI: 10.1186/s40168-020-00817-wGoogle Scholar256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjsVehsbs%253D&md5=90f020cfab898e7e8f0cc61b09ef752eGenetic and metabolic links between the murine microbiome and memoryMao, Jian-Hua; Kim, Young-Mo; Zhou, Yan-Xia; Hu, Dehong; Zhong, Chenhan; Chang, Hang; Brislawn, Colin J.; Fansler, Sarah; Langley, Sasha; Wang, Yunshan; Peisl, B. Y. Loulou; Celniker, Susan E.; Threadgill, David W.; Wilmes, Paul; Orr, Galya; Metz, Thomas O.; Jansson, Janet K.; Snijders, Antoine M.Microbiome (2020), 8 (1), 53CODEN: MICRMP; ISSN:2049-2618. (BioMed Central Ltd.)Recent evidence has linked the gut microbiome to host behavior via the gut-brain axis; however, the underlying mechanisms remain unexplored. A genome-wide assocn. anal. (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly assocd. with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a pos. correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics anal. revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice. Together, this study provides new evidence for a link between Lactobacillus and memory and the results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites.
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257El Hayek, L.; Khalifeh, M.; Zibara, V.; Abi Assaad, R.; Emmanuel, N.; Karnib, N.; El-Ghandour, R.; Nasrallah, P.; Bilen, M.; Ibrahim, P. Lactate Mediates the Effects of Exercise on Learning and Memory through SIRT1-Dependent Activation of Hippocampal Brain-Derived Neurotrophic Factor (BDNF). J. Neurosci. 2019, 39, 2369– 2382, DOI: 10.1523/JNEUROSCI.1661-18.2019Google Scholar257https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cjmtlSquw%253D%253D&md5=70eb44958e8732a7b2373388d184535fLactate Mediates the Effects of Exercise on Learning and Memory through SIRT1-Dependent Activation of Hippocampal Brain-Derived Neurotrophic Factor (BDNF)El Hayek Lauretta; Khalifeh Mohamad; Zibara Victor; Abi Assaad Rawad; Emmanuel Nancy; Karnib Nabil; El-Ghandour Rim; Nasrallah Patrick; Bilen Maria; Ibrahim Pascale; Younes Joe; Abou Haidar Edwina; Barmo Nour; Jabre Vanessa; Sleiman Sama F; Stephan Joseph SThe Journal of neuroscience : the official journal of the Society for Neuroscience (2019), 39 (13), 2369-2382 ISSN:.Exercise promotes learning and memory formation. These effects depend on increases in hippocampal BDNF, a growth factor associated with cognitive improvement and the alleviation of depression symptoms. Identifying molecules that are produced during exercise and that mediate hippocampal Bdnf expression will allow us to harness the therapeutic potential of exercise. Here, we report that an endogenous molecule produced during exercise in male mice induces the Mus musculus Bdnf gene and promotes learning and memory formation. The metabolite lactate, which is released during exercise by the muscles, crosses the blood-brain barrier and induces Bdnf expression and TRKB signaling in the hippocampus. Indeed, we find that lactate-dependent increases in BDNF are associated with improved spatial learning and memory retention. The action of lactate is dependent on the activation of the Sirtuin1 deacetylase. SIRT1 increases the levels of the transcriptional coactivator PGC1a and the secreted molecule FNDC5, known to mediate Bdnf expression. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF, and identify lactate as a potential endogenous molecule that may have therapeutic value for CNS diseases in which BDNF signaling is disrupted.SIGNIFICANCE STATEMENT It is established that exercise promotes learning and memory formation and alleviates the symptoms of depression. These effects are mediated through inducing Bdnf expression and signaling in the hippocampus. Understanding how exercise induces Bdnf and identifying the molecules that mediate this induction will allow us to design therapeutic strategies that can mimic the effects of exercise on the brain, especially for patients with CNS disorders characterized by a decrease in Bdnf expression and who cannot exercise because of their conditions. We identify lactate as an endogenous metabolite that is produced during exercise, crosses the blood-brain barrier and promotes hippocampal dependent learning and memory in a BDNF-dependent manner. Our work identifies lactate as a component of the "exercise pill."
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258Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nature Reviews Gastroenterology & Hepatology 2019, 16, 461– 478, DOI: 10.1038/s41575-019-0157-3Google Scholar258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7pt1Witw%253D%253D&md5=1b468afb50257e2ad98b7cbfb80b7db1The role of short-chain fatty acids in microbiota-gut-brain communicationDalile Boushra; Van Oudenhove Lukas; Verbeke Kristin; Vervliet BramNature reviews. Gastroenterology & hepatology (2019), 16 (8), 461-478 ISSN:.Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.
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259van de Wouw, M.; Boehme, M.; Lyte, J. M.; Wiley, N.; Strain, C.; O’Sullivan, O.; Clarke, G.; Stanton, C.; Dinan, T. G.; Cryan, J. F. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. Journal of Physiology 2018, 596, 4923– 4944, DOI: 10.1113/JP276431Google Scholar259https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsF2lt7jP&md5=550e19112a53fb82de71611be6b0cac6Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterationsvan de Wouw, Marcel; Boehme, Marcus; Lyte, Joshua M.; Wiley, Niamh; Strain, Conall; O'Sullivan, Orla; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.Journal of Physiology (Oxford, United Kingdom) (2018), 596 (20), 4923-4944CODEN: JPHYA7; ISSN:1469-7793. (Wiley-Blackwell)Key points : Chronic (psychosocial) stress changes gut microbiota compn., as well as inducing behavioral and physiol. deficits. The study assess whether short-chain fatty acids (SCFAs) supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixt. of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 wk of repeated psychosocial stress, followed by a comprehensive behavioral anal. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota compn. were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behavior, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addn., SCFAs exhibited behavioral test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body wt. gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota compn. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.
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260Bernasconi, R.; Jones, R. S.; Bittiger, H.; Olpe, H. R.; Heid, J.; Martin, P.; Klein, M.; Loo, P.; Braunwalder, A.; Schmutz, M. Dose pipecolic acid interact with the central GABA-ergic system?. J. Neural Transm. 1986, 67, 175– 189, DOI: 10.1007/BF01243346Google Scholar260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2sXps1Oqsg%253D%253D&md5=b357e9f578d1ab146212cc6b88e6278aDoes pipecolic acid interact with the central GABA-ergic system?Bernasconi, R.; Jones, R. S. G.; Bittiger, H.; Olpe, H. R.; Heid, J.; Martin, P.; Klein, M.; Loo, P.; Braunwalder, A.; Schmutz, M.Journal of Neural Transmission (1972-1989) (1986), 67 (3-4), 175-89CODEN: JNTMAH; ISSN:0300-9564.Several previous studies have suggested a strong GABA [56-12-2]-mimetic action of the endogenous brain imino acid L-pipecolic acid (PA) [3105-95-1]. These observations were evaluated by using electrophysiol. and neurochem. methods on rat cortical neurons in situ. In contrast to published data, only a weak, but bicuculline-sensitive depressant action of PA on cortical neurons was obsd. Furthermore, PA had no affinity for any of the 3 components of the GABA-benzodiazepine-Cl- channel receptor complex. However, in using a modification of published methods, a weak affinity for the GABA-B receptor site was demonstrated [concn. for 50% inhibition (IC50) = 1.8 × 10-3M]. PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15). PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. These results are not compatible with a strong in vivo interaction between PA and GABA-mediated inhibitory transmission.
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261Takahama, K.; Hashimoto, T.; Wang, M. W.; Akaike, N.; Hitoshi, T.; Okano, Y.; Kasé, Y.; Miyata, T. Pipecolic acid enhancement of GABA response in single neurons of rat brain. Neuropharmacology 1986, 25, 339– 342, DOI: 10.1016/0028-3908(86)90263-7Google Scholar261https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL28Xhs1anu7w%253D&md5=9daeb6c15ef8e55e338067a0ab7e0968Pipecolic acid enhancement of GABA response in single neurons of rat brainTakahama, K.; Hashimoto, T.; Wang, M. W.; Akaike, N.; Hitoshi, T.; Okano, Y.; Kase, Y.; Miyata, T.Neuropharmacology (1986), 25 (3), 339-42CODEN: NEPHBW; ISSN:0028-3908.Using unit recording and microelectrophoresis, the influence of pipecolic acid (PA) [535-75-1], a major metabolite of lysine in the brain, on GABA [56-12-2] and glycine [56-40-6] responses was studied in the cerebral cortical and hippocampal pyramidal neurons of rats. With small currents, PA had no effect on the single neuron activities but enhanced GABA response without affecting glycine response. Thus, PA may have a connection with central GABA system.
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262Braniste, V.; Al-Asmakh, M.; Kowal, C.; Anuar, F.; Abbaspour, A.; Tóth, M.; Korecka, A.; Bakocevic, N.; Ng, L. G.; Kundu, P. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 2014, 6, 263ra158– 263ra158, DOI: 10.1126/scitranslmed.3009759Google ScholarThere is no corresponding record for this reference.
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263Li, H.; Sun, J.; Wang, F.; Ding, G.; Chen, W.; Fang, R.; Yao, Y.; Pang, M.; Lu, Z. Q.; Liu, J. Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice. Brain Res. 2016, 1642, 70– 78, DOI: 10.1016/j.brainres.2016.03.031Google Scholar263https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xlt1Snurc%253D&md5=910e9dfb5b484f26d1bd2f2140b3a31bSodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury miceLi, Haixiao; Sun, Jing; Wang, Fangyan; Ding, Guoqiang; Chen, Wenqian; Fang, Renchi; Yao, Ye; Pang, Mengqi; Lu, Zhong-Qiu; Liu, JiamingBrain Research (2016), 1642 (), 70-78CODEN: BRREAP; ISSN:0006-8993. (Elsevier B.V.)Sodium butyrate (SB) has been widely used to treat cerebral diseases. The aim of the present study is to examine the neuroprotective effects of SB on early TBI in mice and to explore the underlying mechanisms of these effects. TBI was induced using a modified wt.-drop method. Neurol. deficits were evaluated according to the neurol. severity score (NSS), brain edema was measured by brain water content, and blood-brain barrier (BBB) permeability was evaluated by Evans blue (EB) dye extravasation. Neuronal injury was assessed by hematoxylin and eosin (H&E) staining and Fluoro-Jade C staining. The expression of tight junction-assocd. proteins, such as occludin and zonula occludens-1 (ZO-1), was analyzed by western blotting and immunofluorescence. Our results showed that mice subjected to TBI exhibited worsened NSS, brain edema, neuronal damage and BBB permeability. However, these were all attenuated by SB. Moreover, SB reversed the decrease in occludin and ZO-1 expression induced by TBI. These findings suggest that SB might attenuate neurol. deficits, brain edema, neuronal change and BBB damage, as well as increase occludin and ZO-1 expression in the brain to protect against TBI. The protective effect of SB may be correlated with restoring the BBB following its impairment.
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264Hoyles, L.; Snelling, T.; Umlai, U.-K.; Nicholson, J. K.; Carding, S. R.; Glen, R. C.; McArthur, S. Microbiome–host systems interactions: protective effects of propionate upon the blood–brain barrier. Microbiome 2018, 6, 55, DOI: 10.1186/s40168-018-0439-yGoogle Scholar264https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MnjsVyrtw%253D%253D&md5=37554bb850a120a8702d86617f653e97Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrierHoyles Lesley; Snelling Tom; Umlai Umm-Kulthum; Nicholson Jeremy K; Glen Robert C; Carding Simon R; Carding Simon R; Glen Robert C; McArthur SimonMicrobiome (2018), 6 (1), 55 ISSN:.BACKGROUND: Gut microbiota composition and function are symbiotically linked with host health and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, and the blood-brain barrier (BBB) also contribute to the gut-brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed. RESULTS: After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signalling. CONCLUSIONS: Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut-brain axis that warrants further attention.
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265Quinn, M.; McMillin, M.; Galindo, C.; Frampton, G.; Pae, H. Y.; DeMorrow, S. Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms. Dig. Liver Dis. 2014, 46, 527– 534, DOI: 10.1016/j.dld.2014.01.159Google Scholar265https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksFWqsbg%253D&md5=9d94f4f86f1d08329d3e0bea7067acf6Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanismsQuinn, Matthew; McMillin, Matthew; Galindo, Cheryl; Frampton, Gabriel; Pae, Hae Yong; DeMorrow, SharonDigestive and Liver Disease (2014), 46 (6), 527-534CODEN: DLDIFK; ISSN:1590-8658. (Elsevier B.V.)The blood brain barrier tightly regulates the passage of mols. into the brain and becomes leaky following obstructive cholestasis. The aim of this study was to det. if increased serum bile acids obsd. during cholestasis permeabilize the blood brain barrier. Rats underwent bile duct ligation or deoxycholic or chenodeoxycholic acid injections and blood brain barrier permeability assessed. In vitro, the permeability of rat brain microvessel endothelial cell monolayers, the expression and phosphorylation of occludin, ZO-1 and ZO-2 as well as the activity of Rac1 was assessed after treatment with plasma from cholestatic rats, or bile acid treatment, in the presence of a Rac1 inhibitor. Blood brain barrier permeability was increased in vivo and in vitro following bile duct ligation or treatment with bile acids. Assocd. with the bile acid-stimulated increase in endothelial cell monolayer permeability was elevated Rac1 activity and increased phosphorylation of occludin. Pretreatment of endothelial cell monolayers with a Rac1 inhibitor prevented the effects of bile acid treatment on occludin phosphorylation and monolayer permeability. These data suggest that increased circulating serum bile acids may contribute to the increased permeability of the blood brain barrier seen during obstructive cholestasis via disruption of tight junctions.
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266Palmela, I.; Correia, L.; Silva, R. F. M.; Sasaki, H.; Kim, K. S.; Brites, D.; Brito, M. A. Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study. Front. Neurosci. 2015, 9, 80, DOI: 10.3389/fnins.2015.00080Google Scholar266https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2Mnpt1SjsA%253D%253D&md5=9b3c6fabb43315c5be8406d37695a53cHydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro studyPalmela Ines; Correia Leonor; Silva Rui F M; Brites Dora; Brito Maria A; Sasaki Hiroyuki; Kim Kwang SFrontiers in neuroscience (2015), 9 (), 80 ISSN:1662-4548.Ursodeoxycholic acid and its main conjugate glycoursodeoxycholic acid are bile acids with neuroprotective properties. Our previous studies demonstrated their anti-apoptotic, anti-inflammatory, and antioxidant properties in neural cells exposed to elevated levels of unconjugated bilirubin (UCB) as in severe jaundice. In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular endothelial cells, UCB has shown to induce caspase-3 activation and cell death, as well as interleukin-6 release and a loss of blood-brain barrier integrity. Here, we tested the preventive and restorative effects of these bile acids regarding the disruption of blood-brain barrier properties by UCB in in vitro conditions mimicking severe neonatal hyperbilirubinemia and using the same experimental blood-brain barrier model. Both bile acids reduced the apoptotic cell death induced by UCB, but only glycoursodeoxycholic acid significantly counteracted caspase-3 activation. Bile acids also prevented the upregulation of interleukin-6 mRNA, whereas only ursodeoxycholic acid abrogated cytokine release. Regarding barrier integrity, only ursodeoxycholic acid abrogated UCB-induced barrier permeability. Better protective effects were obtained by bile acid pre-treatment, but a strong efficacy was still observed by their addition after UCB treatment. Finally, both bile acids showed ability to cross confluent monolayers of human brain microvascular endothelial cells in a time-dependent manner. Collectively, data disclose a therapeutic time-window for preventive and restorative effects of ursodeoxycholic acid and glycoursodeoxycholic acid against UCB-induced blood-brain barrier disruption and damage to human brain microvascular endothelial cells.
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267Hoyles, L.; Pontifex, M. G.; Rodriguez-Ramiro, I.; Anis-Alavi, M. A.; Jelane, K. S.; Snelling, T.; Solito, E.; Fonseca, S.; Carvalho, A. L.; Carding, S. R. Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome 2021, 9, 235, DOI: 10.1186/s40168-021-01181-zGoogle Scholar267https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjsVChtLo%253D&md5=469ad302a3b94bbc45f69521cabcbd54Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxideHoyles, Lesley; Pontifex, Matthew G.; Rodriguez-Ramiro, Ildefonso; Anis-Alavi, M. Areeb; Jelane, Khadija S.; Snelling, Tom; Solito, Egle; Fonseca, Sonia; Carvalho, Ana L.; Carding, Simon R.; Muller, Michael; Glen, Robert C.; Vauzour, David; McArthur, SimonMicrobiome (2021), 9 (1), 235CODEN: MICRMP; ISSN:2049-2618. (BioMed Central Ltd.)Communication between the gut microbiota and the brain is primarily mediated via sol. microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metab. of dietary choline and L-carnitine have received attention due to their proposed assocn. with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. Here, we use an integrated in vitro/in vivo approach to show that physiol. relevant concns. of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. Our findings demonstrate the mechanisms through which microbiome-assocd. methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function.
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268Magistretti, P. J.; Allaman, I. A cellular perspective on brain energy metabolism and functional imaging. Neuron 2015, 86, 883– 901, DOI: 10.1016/j.neuron.2015.03.035Google Scholar268https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpt1Snu7w%253D&md5=7bf55bdc98f4e3aa87f2abdcd469a04bA Cellular Perspective on Brain Energy Metabolism and Functional ImagingMagistretti, Pierre J.; Allaman, IgorNeuron (2015), 86 (4), 883-901CODEN: NERNET; ISSN:0896-6273. (Cell Press)The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is assocd. with an increased glucose utilization and expression of energy metab. genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technol. advances in metabolic studies with cellular resoln. have afforded decisive insights into the understanding of the cellular and mol. bases of the coupling between neuronal activity and energy metab. and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metab. across resoln. scales.
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269Wyss, M. T.; Jolivet, R.; Buck, A.; Magistretti, P. J.; Weber, B. In Vivo Evidence for Lactate as a Neuronal Energy Source. J. Neurosci. 2011, 31, 7477– 7485, DOI: 10.1523/JNEUROSCI.0415-11.2011Google Scholar269https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvFektLk%253D&md5=0be6e0e78737d934d61b108b3cca336dIn vivo evidence for lactate as a neuronal energy sourceWyss, Matthias T.; Jolivet, Renaud; Buck, Alfred; Magistretti, Pierre J.; Weber, BrunoJournal of Neuroscience (2011), 31 (20), 7477-7485CODEN: JNRSDS; ISSN:0270-6474. (Society for Neuroscience)Cerebral energy metab. is a highly compartmentalized and complex process in which transcellular trafficking of metabolites plays a pivotal role. Over the past decade, a role for lactate in fueling the energetic requirements of neurons has emerged. Furthermore, a neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported. The majority of the current evidence concerning lactate metab. at the cellular level is based on in vitro data; only a few recent in vivo results have demonstrated that the brain preferentially utilizes lactate over glucose. Using voltage-sensitive dye (VSD) imaging, beta-probe measurements of radiotracer kinetics, and brain activation by sensory stimulation in the anesthetized rat, we investigated several aspects of cerebral lactate metab. The present study is the first in vivo demonstration of the maintenance of neuronal activity in the presence of lactate as the primary energy source. The loss of the voltage-sensitive dye signal found during severe insulin-induced hypoglycemia is completely prevented by lactate infusion. Thus, lactate has a direct neuroprotective effect. Furthermore, we demonstrate that the brain readily oxidizes lactate in an activity-dependent manner. The washout of 1-[11C]L-lactate, reflecting cerebral lactate oxidn., was obsd. to increase during brain activation from 0.077 ± 0.009 to 0.105 ± 0.007 min-1. Finally, our data confirm that the brain prefers lactate over glucose as an energy substrate when both substrates are available. Using [18F]fluorodeoxyglucose (FDG) to measure the local cerebral metabolic rate of glucose, we demonstrated a lactate concn.-dependent redn. of cerebral glucose utilization during exptl. increased plasma lactate levels.
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270Liu, Z.; Dai, X.; Zhang, H.; Shi, R.; Hui, Y.; Jin, X.; Zhang, W.; Wang, L.; Wang, Q.; Wang, D. Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat. Commun. 2020, 11, 855, DOI: 10.1038/s41467-020-14676-4Google Scholar270https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvFaju7g%253D&md5=baf7abe48bb0c1b76b754d056b8b6f0fGut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairmentLiu, Zhigang; Dai, Xiaoshuang; Zhang, Hongbo; Shi, Renjie; Hui, Yan; Jin, Xin; Zhang, Wentong; Wang, Luanfeng; Wang, Qianxu; Wang, Danna; Wang, Jia; Tan, Xintong; Ren, Bo; Liu, Xiaoning; Zhao, Tong; Wang, Jiamin; Pan, Junru; Yuan, Tian; Chu, Chuanqi; Lan, Lei; Yin, Fei; Cadenas, Enrique; Shi, Lin; Zhao, Shancen; Liu, XueboNature Communications (2020), 11 (1), 855CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metab. gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are obsd. between IF affected genes, microbiota and metabolites, as assessed by integrative modeling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metab.-implicated cognitive pathophysiologies.
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271Russell, W. R.; Hoyles, L.; Flint, H. J.; Dumas, M. E. Colonic bacterial metabolites and human health. Curr. Opin. Microbiol. 2013, 16, 246– 254, DOI: 10.1016/j.mib.2013.07.002Google Scholar271https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFGmu7nE&md5=4cee9b9ceb1c0f330914643a1cb9eaf7Colonic bacterial metabolites and human healthRussell, Wendy R.; Hoyles, Lesley; Flint, Harry J.; Dumas, Marc-EmmanuelCurrent Opinion in Microbiology (2013), 16 (3), 246-254CODEN: COMIF7; ISSN:1369-5274. (Elsevier Ltd.)A review. The influence of the microbial-mammalian metabolic axis is becoming increasingly important for human health. Bacterial fermn. of carbohydrates (CHOs) and proteins produces short-chain fatty acids (SCFA) and a range of other metabolites including those from arom. amino acid (AAA) fermn. SCFA influence host health as energy sources and via multiple signalling mechanisms. Bacterial transformation of fiber-related phytochems. is assocd. with a reduced incidence of several chronic diseases. The 'gut-liver axis' is an emerging area of study. Microbial deconjugation of xenobiotics and release of arom. moieties into the colon can have a wide range of physiol. consequences. In addn., the role of the gut microbiota in choline deficiency in non-alc. fatty liver disease (NAFLD) and insulin resistance is receiving increased attention.
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272Ren, Z.; Zhang, R.; Li, Y.; Li, Y.; Yang, Z.; Yang, H. Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo. Int. J. Mol. Med. 2017, 40, 1444– 1456, DOI: 10.3892/ijmm.2017.3127Google Scholar272https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOru77I&md5=dddc5fbf640e21cdd583d583e1bdecafFerulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivoRen, Zhongkun; Zhang, Rongping; Li, Yuanyuan; Li, Yu; Yang, Zhiyong; Yang, HuiInternational Journal of Molecular Medicine (2017), 40 (5), 1444-1456CODEN: IJMMFG; ISSN:1791-244X. (Spandidos Publications Ltd.)Ferulic acid (FA) is a deriv. of cinnamic acid. It is used in the treatment of heart head blood-vessel disease and exerts protective effects against hypoxia/ischemiainduced cell injury in the brain. This study investigated the potential neuroprotective effects of FA against ischemia/reperfusion (I/R)-induced brain injury in vivo and in vitro through hematoxylin and eosin (H&E) and Nissl staining assays, flow cytometry, Hoechst 33258 staining, quant. PCR, western blot anal. and fluorescence microscopic anal. In this study, models of cerebral I/R injury were established using rats and pheochromocytoma (PC-12) cells. The results revealed that treatment with FA significantly attenuated memory impairment, and reduced hippocampal neuronal apoptosis and oxidative stress in a dose-dependent manner. The results from in vitro expts. also indicated that FA protected the PC-12 cells against I/R-induced reactive oxygen species (ROS) generation and apoptosis by inhibiting apoptosis, Ca2+ influx, superoxide anion (O2-), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) prodn. in a concn.-dependent manner. Moreover, FA inactivated the Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway. MyD88 overexpression abolished the neuroprotective effects of FA. On the whole, we found that FA attenuated memory dysfunction and exerted protective effects against oxidative stress and apoptosis induced by I/R injury by inhibiting the TLR4/MyD88 signaling pathway. This study supports the view that FA may be a promising neuroprotective agent for use in the treatment of cerebral ischemia.
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273Zeni, A. L. B.; Camargo, A.; Dalmagro, A. P. Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice. Steroids 2017, 125, 131– 136, DOI: 10.1016/j.steroids.2017.07.006Google Scholar273https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1enur%252FO&md5=10737f509116132ad93f8b214023939bFerulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in miceZeni, Ana Lucia Bertarello; Camargo, Anderson; Dalmagro, Ana PaulaSteroids (2017), 125 (), 131-136CODEN: STEDAM; ISSN:0039-128X. (Elsevier)Corticosterone (CORT) treatment has been evidenced to develop a depression-like state in animals, that mimic hypothalamic-pituitary-adrenal (HPA)-axis dysregulation implicated in the development of depression. The present study aimed to examine the ferulic acid (FA), a natural phenolic compd., antidepressant and antioxidant activities on the CORT chronic model. Mice orally treated with 20 mg/kg of CORT for 21 days were considered control group, while mice treated with FA (1 mg/kg) or fluoxetine (10 mg/kg) for the last week of CORT treatment, as drug groups. Three weeks of CORT treatment resulted in depressive-like behavior, as indicated by the increase on the immobility time in the tail suspension test, grooming in the splash test and an increase in the oxidative stress markers in the brain. It was obsd. that FA ameliorated the behavioral and oxidative stress alterations induced by CORT, which may plausibly suggest a mode of action for the FA antidepressant effect. The involvement of FA repairing the stress caused by HPA-axis dysfunction evidenced that this phenolic acid could be further investigated as a novel potential agent to improve the management of depression.
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274Verzelloni, E.; Pellacani, C.; Tagliazucchi, D.; Tagliaferri, S.; Calani, L.; Costa, L. G.; Brighenti, F.; Borges, G.; Crozier, A.; Conte, A. Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites. Mol. Nutr. Food Res. 2011, 55, S35– S43, DOI: 10.1002/mnfr.201000525Google Scholar274https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFSltL%252FP&md5=adb4a1bb4d6f2975226d86847520f2f6Antiglycative and neuroprotective activity of colon-derived polyphenol catabolitesVerzelloni, Elena; Pellacani, Claudia; Tagliazucchi, Davide; Tagliaferri, Sara; Calani, Luca; Costa, Lucio G.; Brighenti, Furio; Borges, Gina; Crozier, Alan; Conte, Angela; Del Rio, DanieleMolecular Nutrition & Food Research (2011), 55 (Suppl. 1), S35-S43CODEN: MNFRCV; ISSN:1613-4125. (Wiley-VCH Verlag GmbH & Co. KGaA)Scope: Dietary flavonoids and allied phenolic compds. are thought to be beneficial in the control of diabetes and its complications, because of their ability to inhibit oxidative stress, protein glycation and to act as neuroprotectants. Following ingestion by humans, polyphenolic compds. entering the large intestine undergo extensive metab. by interaction with colonic microbiota and it is metabolites and catabolites of the parent compds. that enter the circulatory system. The aim of this study was to investigate the inhibitory activity of some colonic microbiota-derived polyphenol catabolites against advanced glycation endproducts formation in vitro and to det. their ability, at physiol. concns., to counteract mild oxidative stress of cultured human neuron cells. Methods and results: This study demonstrated that ellagitannin-derived catabolites (urolithins and pyrogallol) are the most effective antiglycative agents, whereas chlorogenic acid-derived catabolites (dihydrocaffeic acid, dihydroferulic acid and feruloylglycine) were most effective in combination in protecting neuronal cells in a conservative in vitro exptl. model. Conclusion: Some polyphenolic catabolites, generated in vivo in the colon, were able in vitro to counteract two key features of diabetic complications, i.e. protein glycation and neurodegeneration. These observations could lead to a better control of these events, which are usually correlated with hyperglycemia.
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275Macfarlane, S.; Macfarlane, G. T. Regulation of short-chain fatty acid production. Proc. Nutr. Soc. 2003, 62, 67– 72, DOI: 10.1079/PNS2002207Google Scholar275https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjslyhtLc%253D&md5=eae7e43433cdbec5bc8b1f3bb3ef482eSession: Short-chain fatty acids. Regulation of short-chain fatty acid productionMacfarlane, Sandra; Macfarlane, Georgia T.Proceedings of the Nutrition Society (2003), 62 (1), 67-72CODEN: PNUSA4; ISSN:0029-6651. (CABI Publishing)A review. Short-chain fatty acid (SCFA) formation by intestinal bacteria is regulated by many different host, environmental, dietary, and microbiol. factors. Substrate availability, bacterial species compn. of the intestinal microflora, and intestinal transit time largely det. the amts. and types of SCFA produced in healthy individuals. Most SCFA in the gut are derived from bacterial breakdown of complex dietary carbohydrates, esp. in the proximal bowel, but digestion of proteins and peptides makes an increasing contribution to SCFA prodn. as food residues pass through the bowel. Bacterial hydrogen metab. also affects the way in which SCFA are made. This can be seen through the effects of inorg. electron acceptors (nitrate, sulfate) on fermn. processes, where they facilitate the formation of more oxidized SCFA such as acetate, at the expense of more reduced fatty acids, such as butyrate. Chemostat studies with pure cultures of saccharolytic gut microorganisms show that carbon availability and growth rate strongly affect the outcome of fermn. Acetate and formate are the major bifidobacterial fermn. products formed during growth under carbon sources limitation, whereas acetate and lactate are produced when carbohydrate is in excess. Lactate is also used as an electron sink in Clostridium perfringens and, to a lesser extent, in Bacteroides fragilis. In the latter microorganism, acetate and succinate are the major fermn. products when substrate is abundant, whereas succinate is decarboxylated to propionate when carbon and energy sources are limiting.
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276Thomas, C. M.; Hong, T.; van Pijkeren, J. P.; Hemarajata, P.; Trinh, D. V.; Hu, W.; Britton, R. A.; Kalkum, M.; Versalovic, J. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One 2012, 7, e31951, DOI: 10.1371/journal.pone.0031951Google Scholar276https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjsVejtbw%253D&md5=c53235a29e18762b542e36e29688a2c5Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signalingThomas, Carissa M.; Hong, Teresa; van Pijkeren, Jan Peter; Hemarajata, Peera; Trinh, Dan V.; Hu, Weidong; Britton, Robert A.; Kalkum, Markus; Versalovic, JamesPLoS One (2012), 7 (2), e31951CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biol. active compds. that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compd.(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liq. chromatog.-high performance liq. chromatog. (HILIC-HPLC) sepn. isolated TNF-inhibitory compds., and HILIC-HPLC fraction compn. was detd. by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from -histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in prodn. of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF prodn. via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF prodn. by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, -histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF prodn. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.
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277De Biase, D.; Pennacchietti, E. Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operon. Mol. Microbiol. 2012, 86, 770– 786, DOI: 10.1111/mmi.12020Google Scholar277https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFyqsrk%253D&md5=fbe249895db7344d75729f206fb33ee1Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operonDe Biase, Daniela; Pennacchietti, EugeniaMolecular Microbiology (2012), 86 (4), 770-786CODEN: MOMIEE; ISSN:0950-382X. (Wiley-Blackwell)A review. For successful colonization of the mammalian host, orally acquired bacteria must overcome the extreme acidic stress (pH < 2.5) encountered during transit through the host stomach. The glutamate-dependent acid resistance (GDAR) system is by far the most potent acid resistance system in commensal and pathogenic Escherichia coli, Shigella flexneri, Listeria monocytogenes and Lactococcus lactis. GDAR requires the activity of glutamate decarboxylase (GadB), an intracellular PLP-dependent enzyme which performs a proton-consuming decarboxylation reaction, and of the cognate antiporter (GadC), which performs the glutamatein/γ-aminobutyrateout (GABA) electrogenic antiport. Here, the authors review recent findings on the structural determinants responsible for pH-dependent intracellular activation of E. coli GadB and GadC. A survey of genomes of bacteria (pathogenic and non-pathogenic), having in common the ability to colonize or to transit through the host gut, shows that the gadB and gadC genes frequently lie next or near each other. This gene arrangement is likely to be important to ensure timely co-regulation of the decarboxylase and the antiporter. Besides the involvement in acid resistance, GABA prodn. and release were found to occur at very high levels in lactic acid bacteria originally isolated from traditionally fermented foods, supporting the evidence that GABA-enriched foods possess health-promoting properties.
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278Zhou, L.; Zeng, Y.; Zhang, H.; Ma, Y. The Role of Gastrointestinal Microbiota in Functional Dyspepsia: A Review. Front. Physiol. 2022, 13, 910568, DOI: 10.3389/fphys.2022.910568Google Scholar278https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MfgsFylsA%253D%253D&md5=aaaf7f23983276192a7afe1dd6083e06The Role of Gastrointestinal Microbiota in Functional Dyspepsia: A ReviewZhou Li; Ma Yan; Zeng Yi; Zhang HongxingFrontiers in physiology (2022), 13 (), 910568 ISSN:1664-042X.Functional dyspepsia is a clinically common functional gastrointestinal disorder with a high prevalence, high impact and high consumption of medical resources. The microbiota in the gastrointestinal tract is a large number of families and is one of the most complex microbial reservoirs in the human body. An increasing number of studies have confirmed the close association between dysbiosis of the gastrointestinal microbiota and the occurrence and progression of functional dyspepsia. Therefore, we reviewed the role of dysbiosis of the gastrointestinal microbiota, H. pylori infection and gastrointestinal microbiota metabolites in functional dyspepsia, focusing on the possible mechanisms by which dysbiosis of the gastrointestinal microbiota contributes to the pathogenesis of functional dyspepsia. Several studies have confirmed that dysbiosis of the gastrointestinal microbiota may cause the occurrence and progression of functional dyspepsia by disrupting the biological barrier of the intestinal mucosa, by disturbing the immune function of the intestinal mucosa, or by causing dysregulation of the microbial-gut-brain axis. Probiotics and antibiotics have also been chosen to treat functional dyspepsia in clinical studies and have shown some improvement in the clinical symptoms. However, more studies are needed to explore and confirm the relationship between dysbiosis of the gastrointestinal microbiota and the occurrence and progression of functional dyspepsia, and more clinical studies are needed to confirm the therapeutic efficacy of microbiota modulation for functional dyspepsia.
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279Alexandrov, P. N.; Hill, J. M.; Zhao, Y.; Bond, T.; Taylor, C. M.; Percy, M. E.; Li, W.; Lukiw, W. J. Aluminum-induced generation of lipopolysaccharide (LPS) from the human gastrointestinal (GI)-tract microbiome-resident Bacteroides fragilis. J. Inorg. Biochem. 2020, 203, 110886, DOI: 10.1016/j.jinorgbio.2019.110886Google Scholar279https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFGqsbvE&md5=29d04279adbb1aeb6db878f1517cac28Aluminum-induced generation of lipopolysaccharide (LPS) from the human gastrointestinal (GI)-tract microbiome-resident Bacteroides fragilisAlexandrov, P. N.; Hill, J. M.; Zhao, Y.; Bond, T.; Taylor, C. M.; Percy, M. E.; Li, W.; Lukiw, W. J.Journal of Inorganic Biochemistry (2020), 203 (), 110886CODEN: JIBIDJ; ISSN:0162-0134. (Elsevier)Gram-neg. bacteria of the human gastrointestinal (GI) tract microbiome: (i) are capable of generating a broad-spectrum of highly neurotoxic, pro-inflammatory and potentially pathogenic mols.; and (ii) these include a highly immunogenic class of amphipathic surface glycolipids known as lipopolysaccharide (LPS). Bacteroides fragilis (B. fragilis), a commensal, Gram neg., non-motile, non-spore forming obligatory anaerobic bacillus, and one of the most abundant bacteria found in the human GI tract, produces a particularly pro-inflammatory and neurotoxic LPS (BF-LPS). BF-LPS: (i) is known to be secreted from the B. fragilis outer membrane into the external-medium; (ii) can damage biophysiol. barriers via cleavage of zonula adherens cell-cell adhesion proteins, thereby disrupting both the GI-tract barrier and the blood-brain barrier (BBB); (iii) is able to transit GI-tract barriers into the systemic circulation and cross the BBB into the human CNS; and (iv) accumulates within CNS neurons in neurodegenerative disorders such as Alzheimer's disease (AD). This short communication provides evidence that the incubation of B. fragilis with aluminum sulfate [Al2(SO4)3] is a potent inducer of BF-LPS. The results suggest for the first time that the pro-inflammatory properties of aluminum may not only be propagated by aluminum itself, but by a stimulation in the prodn. of microbiome-derived BF-LPS and other pro-inflammatory pathogenic microbial products normally secreted from human GI-tract-resident microorganisms.
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280Brown, E. M.; Ke, X.; Hitchcock, D.; Jeanfavre, S.; Avila-Pacheco, J.; Nakata, T.; Arthur, T. D.; Fornelos, N.; Heim, C.; Franzosa, E. A. Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis. Cell Host Microbe 2019, 25, 668– 680.e67, DOI: 10.1016/j.chom.2019.04.002Google Scholar280https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXptFCjsb8%253D&md5=9066af01c7cbaffe9d96bb1c2f9aaf37Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and SymbiosisBrown, Eric M.; Ke, Xiaobo; Hitchcock, Daniel; Jeanfavre, Sarah; Avila-Pacheco, Julian; Nakata, Toru; Arthur, Timothy D.; Fornelos, Nadine; Heim, Cortney; Franzosa, Eric A.; Watson, Nicki; Huttenhower, Curtis; Haiser, Henry J.; Dillow, Glen; Graham, Daniel B.; Finlay, B. Brett; Kostic, Aleksandar D.; Porter, Jeffrey A.; Vlamakis, Hera; Clish, Clary B.; Xavier, Ramnik J.Cell Host & Microbe (2019), 25 (5), 668-680.e7CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)Sphingolipids are structural membrane components and important eukaryotic signaling mols. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentially abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipids, but the impact of these metabolites on host pathways is largely uncharacterized. To det. whether bacterial sphingolipids modulate intestinal health, we colonized germ-free mice with a sphingolipid-deficient Bacteroides thetaiotaomicron strain. A lack of Bacteroides-derived sphingolipids resulted in intestinal inflammation and altered host ceramide pools in mice. Using lipidomic anal., we described a sphingolipid biosynthesis pathway and revealed a variety of Bacteroides-derived sphingolipids including ceramide phosphoinositol and deoxy-sphingolipids. Annotating Bacteroides sphingolipids in an IBD metabolomic dataset revealed lower abundances in IBD and neg. correlations with inflammation and host sphingolipid prodn. These data highlight the role of bacterial sphingolipids in maintaining homeostasis and symbiosis in the gut.
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281Gao, K.; Pi, Y.; Mu, C. L.; Farzi, A.; Liu, Z.; Zhu, W. Y. Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota-brain axis. J. Neurochem. 2019, 149, 641– 659, DOI: 10.1111/jnc.14709Google Scholar281https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpsFagu70%253D&md5=5c44d1a907a9a89e54e338ac136a4b92Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota-brain axisGao, Kan; Pi, Yu; Mu, Chun-Long; Farzi, Aitak; Liu, Zhuang; Zhu, Wei-YunJournal of Neurochemistry (2019), 149 (5), 641-659CODEN: JONRA9; ISSN:0022-3042. (Wiley-Blackwell)The gut microbiota is increasingly recognized to modulate brain function by recent studies demonstrating the central effects of various gut microbial manipulation strategies. Our previous study demonstrated that antibiotic-induced alterations of hindgut microbiota are assocd. with changes in arom. amino acid (AAA) metab. and hypothalamic neurochem., while the underlying mechanistic insight is limited. Given that the microbial AAA metab. can be affected by luminal carbohydrate availability, here we hypothesize that increasing hindgut carbohydrate availability affects the expression of neurotransmitters in the porcine hypothalamus. A hindgut microbiota-targeted strategy was adopted by increasing hindgut carbohydrate availability in a cecal-cannulated piglet model. Mechanistic involvement of AAAs along the gut microbiota-brain axis was further investigated in mice and neuronal cells. Increasing carbohydrate availability by cecal starch infusion led to a decrease in hindgut AAA metab., and an increase in systemic AAA availability, central AAA-derived neurotransmitters (5-HT, dopamine), and neurotrophin BDNF in piglets, indicating that hindgut microbiota affect hypothalamic neurochem. in an AAA-dependent manner. Single AAA i.p. injection in mice revealed that an increase in circulating tryptophan and tyrosine elevated their concns. in brain and finally promoted the expressions of 5-HT, dopamine, and BDNF in a time-dependent manner. Neuronal cells treated with single AAAs in vitro further demonstrated that tryptophan and tyrosine enhanced 5-HT and dopamine synthesis, resp., and promoted BDNF expression partly through the 5-HT1A/DRD1-CREB pathway. Our study reveals that increasing hindgut carbohydrate availability promotes hypothalamic neurotransmitter synthesis and that AAAs act as potential mediators between hindgut microbiota and brain neurochem.
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282Gao, K.; Mu, C.-l.; Farzi, A.; Zhu, W.-y. Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. Adv. Nutr. 2020, 11, 709– 723, DOI: 10.1093/advances/nmz127Google Scholar282https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MfovFarug%253D%253D&md5=517971632b0589cd171716d960b396a5Tryptophan Metabolism: A Link Between the Gut Microbiota and BrainGao Kan; Mu Chun-Long; Zhu Wei-Yun; Gao Kan; Mu Chun-Long; Zhu Wei-Yun; Farzi AitakAdvances in nutrition (Bethesda, Md.) (2020), 11 (3), 709-723 ISSN:.The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota. We start by outlining existing knowledge on tryptophan metabolism, including serotonin synthesis and degradation pathways of the host, and summarize recent advances in demonstrating the influence of the gut microbiota on tryptophan metabolism. The latest evidence revealing those mechanisms by which the gut microbiota modulates tryptophan metabolism, with subsequent effects on brain function, is reviewed. Finally, the potential modulation of intestinal tryptophan metabolism as a therapeutic option for brain and GI functional disorders is also discussed.
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283Xiao, L.; Liu, Q.; Luo, M.; Xiong, L. Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome. Frontiers in Cellular and Infection Microbiology 2021, 11, 729346, DOI: 10.3389/fcimb.2021.729346Google Scholar283https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XmslWrtrc%253D&md5=59c88c713d2413d27736a3a03283af9fGut microbiota-derived metabolites in irritable bowel syndromeXiao, Lin; Liu, Qin; Luo, Mei; Xiong, LishouFrontiers in Cellular and Infection Microbiology (2021), 11 (), 729346CODEN: FCIMAB; ISSN:2235-2988. (Frontiers Media S.A.)Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is assocd. with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiol. remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiol. factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, esp. bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.
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284Mawe, G. M.; Hoffman, J. M. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 473– 486, DOI: 10.1038/nrgastro.2013.105Google Scholar284https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1amtLrN&md5=d844a1824e6d6e186e3cb5ad4701cf4bSerotonin signalling in the gut-functions, dysfunctions and therapeutic targetsMawe, Gary M.; Hoffman, Jill M.Nature Reviews Gastroenterology & Hepatology (2013), 10 (8), 473-486CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. Serotonin (5-HT) has been recognized for decades as an important signalling mol. in the gut, but it is still revealing its secrets. Novel gastrointestinal functions of 5-HT continue to be discovered, as well as distant actions of gut-derived 5-HT, and we are learning how 5-HT signalling is altered in gastrointestinal disorders. Conventional functions of 5-HT involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion and vasodilation. Activation of extrinsic vagal and spinal afferent fibers results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts nonconventional actions such as promoting inflammation and serving as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, originating in the gut, promotes haemostasis, influences bone development and serves many other functions. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhoea or constipation, resp., and the synthetic enzyme tryptophan hydroxylase has also been targeted. Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. We provide an overview of these serotonergic actions and treatment strategies.
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285Tan, J.; McKenzie, C.; Potamitis, M.; Thorburn, A. N.; Mackay, C. R.; Macia, L. The role of short-chain fatty acids in health and disease. Adv. Immunol. 2014, 121, 91– 119, DOI: 10.1016/B978-0-12-800100-4.00003-9Google Scholar285https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmslyitbc%253D&md5=406b18dd24f999e71d0043c09c9f0b73The role of short-chain fatty acids in health and diseaseTan, Jian; McKenzie, Craig; Potamitis, Maria; Thorburn, Alison N.; MacKay, Charles R.; Macia, LaurenceAdvances in Immunology (2014), 121 (), 91-119CODEN: ADIMAV; ISSN:0065-2776. (Elsevier Inc.)A review. There is now an abundance of evidence to show that short-chain fatty acids (SCFAs) play an important role in the maintenance of health and the development of disease. SCFAs are a subset of fatty acids that are produced by the gut microbiota during the fermn. of partially and nondigestible polysaccharides. The highest levels of SCFAs are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream. Two major SCFA signaling mechanisms have been identified, inhibition of histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs). Since HDACs regulate gene expression, inhibition of HDACs has a vast array of downstream consequences. Our understanding of SCFA-mediated inhibition of HDACs is still in its infancy. GPCRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have implicated a major role for these GPCRs in the regulation of metab., inflammation, and disease. SCFAs have been shown to alter chemotaxis and phagocytosis; induce reactive oxygen species (ROS); change cell proliferation and function; have anti-inflammatory, antitumorigenic, and antimicrobial effects; and alter gut integrity. These findings highlight the role of SCFAs as a major player in maintenance of gut and immune homeostasis. Given the vast effects of SCFAs, and that their levels are regulated by diet, they provide a new basis to explain the increased prevalence of inflammatory disease in Westernized countries, as highlighted in this chapter.
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286Felizardo, R. J. F.; Watanabe, I. K. M.; Dardi, P.; Rossoni, L. V.; Câmara, N. O. S. The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids. Pharmacol. Res. 2019, 141, 366– 377, DOI: 10.1016/j.phrs.2019.01.019Google Scholar286https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFyksLo%253D&md5=c398cbf6bc9cc75591333d1e01ae7de0The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acidsFelizardo, R. J. F.; Mizuno Watanabe, Ingrid Kazue; Dardi, Patrizia; Venturini Rossoni, Luciana; Olsen Saraiva Camara, NielsPharmacological Research (2019), 141 (), 366-377CODEN: PHMREP; ISSN:1043-6618. (Elsevier Ltd.)A review. The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been assocd. with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely assocd. diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced no. of short-chain fatty acids (SCFAs) producing bacteria is assocd. with modifications in gut environment, involving redn. of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the redn. of SCFAs plasma levels. These modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria compn. and fecal metabolite profile, inducing a pos. feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota compn. can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial compn. uncovering to improve human health maintenance and, esp., for the development of new alternative therapies.
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287Canfora, E. E.; Meex, R. C. R.; Venema, K.; Blaak, E. E. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat. Rev. Endocrinol. 2019, 15, 261– 273, DOI: 10.1038/s41574-019-0156-zGoogle Scholar287https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVyrtrzN&md5=b6bb65904cdce776542156c958c2e0ebGut microbial metabolites in obesity, NAFLD and T2DMCanfora, Emanuel E.; Meex, Ruth C. R.; Venema, Koen; Blaak, Ellen E.Nature Reviews Endocrinology (2019), 15 (5), 261-273CODEN: NREABD; ISSN:1759-5029. (Nature Research)Evidence is accumulating that the gut microbiome is involved in the etiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fiber), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fiber, the major energy source for the microbiota, is limited here. This proteolytic fermn. yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermn. could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermn. in relation to obesity and obesity-assocd. insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.
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288Tahara, Y.; Yamazaki, M.; Sukigara, H.; Motohashi, H.; Sasaki, H.; Miyakawa, H.; Haraguchi, A.; Ikeda, Y.; Fukuda, S.; Shibata, S. Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue. Sci. Rep. 2018, 8, 1395, DOI: 10.1038/s41598-018-19836-7Google Scholar288https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MvjsFKjuw%253D%253D&md5=6333e6b0503509819433c4f1181cae9dGut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral TissueTahara Yu; Yamazaki Mayu; Sukigara Haruna; Motohashi Hiroaki; Sasaki Hiroyuki; Miyakawa Hiroki; Haraguchi Atsushi; Ikeda Yuko; Shibata Shigenobu; Tahara Yu; Fukuda Shinji; Fukuda ShinjiScientific reports (2018), 8 (1), 1395 ISSN:.Microbiota-derived short-chain fatty acids (SCFAs) and organic acids produced by the fermentation of non-digestible fibre can communicate from the microbiome to host tissues and modulate homeostasis in mammals. The microbiome has circadian rhythmicity and helps the host circadian clock function. We investigated the effect of SCFA or fibre-containing diets on circadian clock phase adjustment in mouse peripheral tissues (liver, kidney, and submandibular gland). Initially, caecal SCFA concentrations, particularly acetate and butyrate, induced significant day-night differences at high concentrations during the active period, which were correlated with lower caecal pH. By monitoring luciferase activity correlated with the clock gene Period2 in vivo, we found that oral administration of mixed SCFA (acetate, butyrate, and propionate) and an organic acid (lactate), or single administration of each SCFA or lactate for three days, caused phase changes in the peripheral clocks with stimulation timing dependency. However, this effect was not detected in cultured fibroblasts or cultured liver slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect modulation of circadian clocks in vivo. Finally, cellobiose-containing diets facilitated SCFA production and refeeding-induced peripheral clock entrainment. SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock adjustment, suggesting prebiotics as novel therapeutic candidates for misalignment.
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289Feng, W.; Ao, H.; Peng, C. Gut Microbiota, Short-Chain Fatty Acids, and Herbal Medicines. Front. Pharmacol. 2018, 9, 1354, DOI: 10.3389/fphar.2018.01354Google Scholar289https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVGmt7fM&md5=bb45526d6fcc36ea07eb55386de4e4b0Gut microbiota, short-chain fatty acids, and herbal medicinesFeng, Wuwen; Ao, Hui; Peng, ChengFrontiers in Pharmacology (2018), 9 (), 1354CODEN: FPRHAU; ISSN:1663-9812. (Frontiers Media S.A.)A review. As an important source for traditional medical systems such as Ayurvedic medicine and traditional Chinesemedicine, herbalmedicines have received widespread attentions from all over the world, esp. in developing countries. Over the past decade, studies on gut microbiota have generated rich information for understanding how gut microbiota shape the functioning of our body system. In view of the importance of gutmicrobiota, the researchers engaged in studying herbal medicines have paid more and more attention to gut microbiota and gut microbiota metabolites. Among a variety of gut microbiota metabolites, short-chain fatty acids (SCFAs) have received most attention because of their important role in maintaining the hemostasis of hosts and recovery of diseases. Herbal medicines, as an important resource provider for prodn. of SCFAs, have been demonstrated to be able to modulate gut microbiota compn. and regulate SCFAs prodn. In this mini-review, we summarize current knowledge about SCFAs origination, the role of SCFAs in health and disease, the influence of herbal medicine on SCFAs prodn. and the corresponding mechanisms. At the end of this review, the strategies and suggestions for further research of SCFAs and herbal medicines are also discussed.
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290Pan, L. L.; Li, B. B.; Pan, X. H.; Sun, J. Gut microbiota in pancreatic diseases: possible new therapeutic strategies. Acta Pharmacol. Sin. 2021, 42, 1027– 1039, DOI: 10.1038/s41401-020-00532-0Google Scholar290https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1ersLzI&md5=f5b631fb45a432e9c11987d3ed7eef92Gut microbiota in pancreatic diseases: possible new therapeutic strategiesPan, Li-long; Li, Bin-bin; Pan, Xiao-hua; Sun, JiaActa Pharmacologica Sinica (2021), 42 (7), 1027-1039CODEN: APSCG5; ISSN:1671-4083. (Nature Portfolio)Abstr.: Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential mol. mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clin. potential to reduce the cost of pancreatic diseases.
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291Perino, A.; Demagny, H.; Velazquez-Villegas, L.; Schoonjans, K. Molecular Physiology of Bile Acid Signaling in Health, Disease, and Aging. Physiol. Rev. 2021, 101, 683– 731, DOI: 10.1152/physrev.00049.2019Google Scholar291https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsV2rtLfM&md5=e40a91623bb6a6e5d72940b486bf7207Molecular physiology of bile acid signaling in health, disease, and agingPerino, Alessia; Demagny, Hadrien; Velazquez-Villegas, Laura; Schoonjans, KristinaPhysiological Reviews (2021), 101 (2), 683-731CODEN: PHREA7; ISSN:1522-1210. (American Physiological Society)Over the past two decades, bile acids (BAs) have become established as important signaling mols. that enable fine-tuned inter-tissue communication from the liver, their site of prodn., over the intestine, where they are modified by the gut microbiota, to virtually any organ, where they exert their pleiotropic physiol. effects. The chem. variety of BAs, to a large extent detd. by the gut microbiome, also allows for a complex fine-tuning of adaptive responses in our body. This review provides an overview of the mechanisms by which BA receptors coordinate several aspects of physiol. and highlights new therapeutic strategies for diseases underlying pathol. BA signaling.
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292Wahlström, A.; Sayin, S. I.; Marschall, H. U.; Bäckhed, F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016, 24, 41– 50, DOI: 10.1016/j.cmet.2016.05.005Google Scholar292https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7hsFCksg%253D%253D&md5=4511dc3bf1227613cfc8758c24f3d1c0Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host MetabolismWahlstrom Annika; Sayin Sama I; Marschall Hanns-Ulrich; Backhed FredrikCell metabolism (2016), 24 (1), 41-50 ISSN:.The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition.
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293Poland, J. C.; Flynn, C. R. Bile Acids, Their Receptors, and the Gut Microbiota. Physiology (Bethesda) 2021, 36, 235– 245, DOI: 10.1152/physiol.00028.2020Google Scholar293https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c3hsVagsA%253D%253D&md5=21524b7bd10b81a547092fba07c511aaBile Acids, Their Receptors, and the Gut MicrobiotaPoland James C; Flynn C RobbPhysiology (Bethesda, Md.) (2021), 36 (4), 235-245 ISSN:.Bile acids (BAs) are a family of hydroxylated steroids secreted by the liver that aid in the breakdown and absorption of dietary fats. BAs also function as nutrient and inflammatory signaling molecules, acting through cognate receptors, to coordinate host metabolism. Commensal bacteria in the gastrointestinal tract are functional modifiers of the BA pool, affecting composition and abundance. Deconjugation of host BAs creates a molecular network that inextricably links gut microtia with their host. In this review we highlight the roles of BAs in mediating this mutualistic relationship with a focus on those events that impact host physiology and metabolism.
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294Govindarajan, K.; MacSharry, J.; Casey, P. G.; Shanahan, F.; Joyce, S. A.; Gahan, C. G. M. Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk. PLoS One 2016, 11, e0167319 DOI: 10.1371/journal.pone.0167319Google Scholar294https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXktFaitrg%253D&md5=f9ce0ed944d15813a8e055d849bc5580Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalkGovindarajan, Kalaimathi; MacSharry, John; Casey, Patrick G.; Shanahan, Fergus; Joyce, Susan A.; Gahan, Cormac G. M.PLoS One (2016), 11 (12), e0167319/1-e0167319/13CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Disruptions to circadian rhythm in mice and humans have been assocd. with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiol. regulators of host circadian gene expression. We utilized a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equiv. tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addn. oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and assocd. genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression.
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295McMillin, M.; DeMorrow, S. Effects of bile acids on neurological function and disease. FASEB J. 2016, 30, 3658– 3668, DOI: 10.1096/fj.201600275RGoogle Scholar295https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvV2mtbzK&md5=66ec30bab5f8afd61a577c18a5b12697Effects of bile acids on neurological function and diseaseMcmillin, Matthew; DeMorrow, SharonFASEB Journal (2016), 30 (11), 3658-3668CODEN: FAJOEC; ISSN:0892-6638. (Federation of American Societies for Experimental Biology)Bile acids are synthesized from cholesterol and are known to be involved with the emulsification and digestion of dietary lipids and fat-sol. vitamins. Outside of this role, bile acids can act as cell signaling effectors through binding and activating receptors on both the cell membrane and nucleus. Numerous reports have investigated these signaling pathways in conditions where the liver is damaged. More recently, effort has been made to investigate the role of bile acids in diseases outside of those assocd. with liver damage. This review summarizes recent findings on the influences that bile acids can exert in normal neurol. function and their contribution to diseases of the nervous system, with the intent of highlighting the role of these metabolites as potential players in neurol. disorders.
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296Roth, W.; Zadeh, K.; Vekariya, R.; Ge, Y.; Mohamadzadeh, M. Tryptophan Metabolism and Gut-Brain Homeostasis. Int. J. Mol. Sci. 2021, 22, 2973, DOI: 10.3390/ijms22062973Google Scholar296https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXht1OitL%252FN&md5=2b067a8c7e8ea4f3283bca2798d5f93eTryptophan metabolism and gut-brain homeostasisRoth, William; Zadeh, Kimia; Vekariya, Rushi; Ge, Yong; Mohamadzadeh, MansourInternational Journal of Molecular Sciences (2021), 22 (6), 2973CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)A review. Tryptophan is an essential amino acid crit. for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degrdation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Addnl., tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurol. and psychiatric disorders. Gut microbes influence tryptophan metab. directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurol. and psychiatric disorders where tryptophan and its metabolites play a prominent role. In we will touch upon some of these features and their involvement in health and disease.
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297Zhang, J.; Zhu, S.; Ma, N.; Johnston, L. J.; Wu, C.; Ma, X. Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammation. Med. Res. Rev. 2021, 41, 1061– 1088, DOI: 10.1002/med.21752Google Scholar297https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlvVCgu7g%253D&md5=8f82f6574152862aa3706b034e261b12Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammationZhang, Jie; Zhu, Shengwei; Ma, Ning; Johnston, Lee J.; Wu, Chaodong; Ma, XiMedicinal Research Reviews (2021), 41 (2), 1061-1088CODEN: MRREDD; ISSN:0198-6325. (John Wiley & Sons, Inc.)A review. In a complex, diverse intestinal environment, commensal microbiota metabolizes excessive dietary tryptophan to produce more bioactive metabolites connecting with kinds of diverse process, such as host physiol. defense, homeostasis, excessive immune activation and the progression and outcome of different diseases, such as inflammatory bowel disease, irritable bowel syndrome and others. Although commensal microbiota includes bacteria, fungi, and protozoa and all that, they often have the similar metabolites in tryptophan metab. process via same or different pathways. These metabolites can work as signal to activate the innate immunity of intestinal mucosa and induce the rapid inflammation response. They are crit. in reconstruction of lumen homeostasis as well. This review aims to seek the potential function and mechanism of microbiota-derived tryptophan metabolites as targets to regulate and shape intestinal immune function, which mainly focused on two aspects. First, analyze the character of tryptophan metab. in bacteria, fungi, and protozoa, and assess the functions of their metabolites (including indole and eight other derivs., serotonin (5-HT) and -tryptophan) on regulating the integrity of intestinal epithelium and the immunity of the intestinal mucosa. Second, focus on the mediator and pathway for their recognition, transfer and crosstalk between microbiota-derived tryptophan metabolites and intestinal mucosal immunity. Disruption of intestinal homeostasis has been described in different intestinal inflammatory diseases, available data suggest the remarkable potential of tryptophan-derived aryl hydrocarbon receptor agonists, indole derivs. on lumen equil. These metabolites as preventive and therapeutic interventions have potential to promote proinflammatory or anti-inflammatory responses of the gut.
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298Modoux, M.; Rolhion, N.; Mani, S.; Sokol, H. Tryptophan Metabolism as a Pharmacological Target. Trends Pharmacol. Sci. 2021, 42, 60– 73, DOI: 10.1016/j.tips.2020.11.006Google Scholar298https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVags7bF&md5=8185b6cec8cafad33abfa47edccc14d3Tryptophan Metabolism as a Pharmacological TargetModoux, Morgane; Rolhion, Nathalie; Mani, Sridhar; Sokol, HarryTrends in Pharmacological Sciences (2021), 42 (1), 60-73CODEN: TPHSDY; ISSN:0165-6147. (Elsevier Ltd.)A review. L-Tryptophan is an essential amino acid required for protein synthesis. It undergoes an extensive and complex metab. along several pathways, resulting in many bioactive mols. acting in various organs through different action mechanisms. Enzymes involved in its metab., metabolites themselves, or their receptors, represent potential therapeutic targets, which are the subject of dynamic research. Disruptions in L-tryptophan metab. are reported in several neurol., metabolic, psychiatric, and intestinal disorders, paving the way to develop drugs to target it. This review will briefly describe L-tryptophan metab. and present and discuss the most recent pharmacol. developments targeting it.
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299Roager, H. M.; Licht, T. R. Microbial tryptophan catabolites in health and disease. Nat. Commun. 2018, 9, 3294, DOI: 10.1038/s41467-018-05470-4Google Scholar299https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c7ptlCrtg%253D%253D&md5=7ec59a169558847e494dd14b59447737Microbial tryptophan catabolites in health and diseaseRoager Henrik M; Roager Henrik M; Licht Tine RNature communications (2018), 9 (1), 3294 ISSN:.Accumulating evidence implicates metabolites produced by gut microbes as crucial mediators of diet-induced host-microbial cross-talk. Here, we review emerging data suggesting that microbial tryptophan catabolites resulting from proteolysis are influencing host health. These metabolites are suggested to activate the immune system through binding to the aryl hydrocarbon receptor (AHR), enhance the intestinal epithelial barrier, stimulate gastrointestinal motility, as well as secretion of gut hormones, exert anti-inflammatory, anti-oxidative or toxic effects in systemic circulation, and putatively modulate gut microbial composition. Tryptophan catabolites thus affect various physiological processes and may contribute to intestinal and systemic homeostasis in health and disease.
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300Agus, A.; Planchais, J.; Sokol, H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe 2018, 23, 716– 724, DOI: 10.1016/j.chom.2018.05.003Google Scholar300https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFCqtrjO&md5=690e7ed63e96a101269ff4165f917902Gut Microbiota Regulation of Tryptophan Metabolism in Health and DiseaseAgus, Allison; Planchais, Julien; Sokol, HarryCell Host & Microbe (2018), 23 (6), 716-724CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)A review. The gut microbiota is a crucial actor in human physiol. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host mols. Among the array of metabolites at the interface between these microorganisms and the host is the essential arom. amino acid tryptophan (Trp). In the gut, the three major Trp metab. pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivs. are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metab. in microbiota-host crosstalk in health and disease. Deciphering the complex equil. between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
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301Wang, Z.; Bergeron, N.; Levison, B. S.; Li, X. S.; Chiu, S.; Jia, X.; Koeth, R. A.; Li, L.; Wu, Y.; Tang, W. H. W. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur. Heart J. 2019, 40, 583– 594, DOI: 10.1093/eurheartj/ehy799Google Scholar301https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjsFeks74%253D&md5=63b4295582c8062536b42fbb426e6f53Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and womenWang, Zeneng; Bergeron, Nathalie; Levison, Bruce S.; Li, Xinmin S.; Chiu, Sally; Jia, Xun; Koeth, Robert A.; Li, Lin; Wu, Yuping; Tang, W. H. Wilson; Krauss, Ronald M.; Hazen, Stanley L.European Heart Journal (2019), 40 (7), 583-594CODEN: EHJODF; ISSN:1522-9645. (Oxford University Press)Aims Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metab. and renal excretion. Methods and results Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-satd. fat) crossover design study. Within each arm, three 4-wk isocaloric diets (with washout period between each) were evaluated (all meals prepd. in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metab. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05).
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302Zhang, Y.; Wang, Y.; Ke, B.; Du, J. TMAO: how gut microbiota contributes to heart failure. Transl. Res. 2021, 228, 109– 125, DOI: 10.1016/j.trsl.2020.08.007Google Scholar302https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVeqtLbL&md5=de42e2d7b7c56657dbcd149b1a22e064TMAO: how gut microbiota contributes to heart failureZhang, Yixin; Wang, Yuan; Ke, Bingbing; Du, JieTranslational Research (2021), 228 (), 109-125CODEN: TRRECL; ISSN:1878-1810. (Elsevier B.V.)A review. An increasing amt. of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathol. of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathol. processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gut-TMAO-HF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research.
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303Yang, S.; Li, X.; Yang, F.; Zhao, R.; Pan, X.; Liang, J.; Tian, L.; Li, X.; Liu, L.; Xing, Y. Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target. Front. Pharmacol. 2019, 10, 1360, DOI: 10.3389/fphar.2019.01360Google Scholar303https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs12gsb7F&md5=bb8715d400eb6dcd9c5913c7f3e22cc3Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic TargetYang, Shengjie; Li, Xinye; Yang, Fan; Zhao, Ran; Pan, Xiandu; Liang, Jiaqi; Tian, Li; Li, Xiaoya; Liu, Longtao; Xing, Yanwei; Wu, MinFrontiers in Pharmacology (2019), 10 (), 1360CODEN: FPRHAU; ISSN:1663-9812. (Frontiers Media S.A.)Cardiovascular disease is the leading cause of death worldwide, esp. in developed countries, and atherosclerosis (AS) is the common pathol. basis of many cardiovascular diseases such as coronary heart disease. The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide, an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In this review, we discuss the TMAO-involved mechanisms of atherosclerotic CVD from the perspective of inflammation, inflammation-related immunity, cholesterol metab., and atherothrombosis. We also summarize available clin. studies on the role of TMAO in predicting prognostic outcomes, including major adverse cardiovascular events, in patients presenting with AS. Finally, since TMAO may be a novel therapeutic target for AS, several therapeutic strategies including drugs, dietary, etc. to lower TMAO levels that are currently being explored are also discussed.
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304Rudzki, L.; Stone, T. W.; Maes, M.; Misiak, B.; Samochowiec, J.; Szulc, A. Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021, 107, 110240, DOI: 10.1016/j.pnpbp.2020.110240Google Scholar304https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3svosFGksQ%253D%253D&md5=ae0e6a49e8f1ae5c922b388f898744fdGut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and diseaseRudzki Leszek; Stone Trevor W; Maes Michael; Misiak Blazej; Samochowiec Jerzy; Szulc AgataProgress in neuro-psychopharmacology & biological psychiatry (2021), 107 (), 110240 ISSN:.Despite the well-established roles of B-vitamins and their deficiencies in health and disease, there is growing evidence indicating a key role of those nutrients in functions of the central nervous system and in psychopathology. Clinical data indicate the substantial role of B-vitamins in various psychiatric disorders, including major depression, bipolar disorder, schizophrenia, autism, and dementia, including Alzheimer's and Parkinson's diseases. As enzymatic cofactors, B-vitamins are involved in many physiological processes such as the metabolism of glucose, fatty acids and amino acids, metabolism of tryptophan in the kynurenine pathway, homocysteine metabolism, synthesis and metabolism of various neurotransmitters and neurohormones including serotonin, dopamine, adrenaline, acetylcholine, GABA, glutamate, D-serine, glycine, histamine and melatonin. Those vitamins are highly involved in brain energetic metabolism and respiration at the cellular level. They have a broad range of anti-inflammatory, immunomodulatory, antioxidant and neuroprotective properties. Furthermore, some of those vitamins are involved in the regulation of permeability of the intestinal and blood-brain barriers. Despite the fact that a substantial amount of the above vitamins is acquired from various dietary sources, deficiencies are not uncommon, and it is estimated that micronutrient deficiencies affect about two billion people worldwide. The majority of gut-resident microbes and the broad range of bacteria available in fermented food, express genetic machinery enabling the synthesis and metabolism of B-vitamins and, consequently, intestinal microbiota and fermented food rich in probiotic bacteria are essential sources of B-vitamins for humans. All in all, there is growing evidence that intestinal bacteria-derived vitamins play a significant role in physiology and that dysregulation of the "microbiota-vitamins frontier" is related to various disorders. In this review, we will discuss the role of vitamins in mental health and explore the perspectives and potential of how gut microbiota-derived vitamins could contribute to mental health and psychiatric treatment.
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305Stacchiotti, V.; Rezzi, S.; Eggersdorfer, M.; Galli, F. Metabolic and functional interplay between gut microbiota and fat-soluble vitamins. Crit Rev. Food Sci. Nutr 2021, 61, 3211– 3232, DOI: 10.1080/10408398.2020.1793728Google Scholar305https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsFOiu77P&md5=7cd75a8903603411a5be6c4ee71dacabMetabolic and functional interplay between gut microbiota and fat-soluble vitaminsStacchiotti, Valentina; Rezzi, Serge; Eggersdorfer, Manfred; Galli, FrancescoCritical Reviews in Food Science and Nutrition (2021), 61 (19), 3211-3232CODEN: CRFND6; ISSN:1040-8398. (Taylor & Francis, Inc.)A review. Gut microbiota is a complex ecosystem seen as an extension of human genome. It represents a major metabolic interface of interaction with food components and xenobiotics in the gastrointestinal (GI) environment. In this context, the advent of modern bacterial genome sequencing technol. has enabled the identification of dietary nutrients as key determinants of gut microbial ecosystem able to modulate the host-microbiome symbiotic relationship and its effects on human health. This article provides a literature review on functional and mol. interactions between a specific group of lipids and essential nutrients, e.g., fat-sol. vitamins (FSVs), and the gut microbiota. A two-way relationship appears to emerge from the available literature with important effects on human metab., nutrition, GI physiol. and immune function. First, FSV directly or indirectly modify the microbial compn. involving for example immune system-mediated and/or metabolic mechanisms of bacterial growth or inhibition. Second, the gut microbiota influences at different levels the synthesis, metab. and transport of FSV including their bioactive metabolites that are either introduced with the diet or released in the gut via entero-hepatic circulation. A better understanding of these interactions, and of their impact on intestinal and metabolic homeostasis, will be pivotal to design new and more efficient strategies of disease prevention and therapy, and personalized nutrition.
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306Masri, O. A.; Chalhoub, J. M.; Sharara, A. I. Role of vitamins in gastrointestinal diseases. World J. Gastroenterol. 2015, 21, 5191– 5209, DOI: 10.3748/wjg.v21.i17.5191Google Scholar306https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtFaktr7J&md5=6ef31693fd6f1a30e51d88cde6e6276fRole of vitamins in gastrointestinal diseasesMasri, Omar A.; Chalhoub, Jean M.; Sharara, Ala I.World Journal of Gastroenterology (2015), 21 (17), 5191-5209CODEN: WJGAF2; ISSN:2219-2840. (Baishideng Publishing Group Inc.)A tremendous amt. of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with nonalcoholic steatohepatitis, the additive role of vitamins B12 and D to the std. therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the pos. outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychol. accepted by patients as a natural compd. with relative safety and low cost, their use should be encouraged in the fields where pos. data are available.
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307McCarville, J. L.; Chen, G. Y.; Cuevas, V. D.; Troha, K.; Ayres, J. S. Microbiota Metabolites in Health and Disease. Annu. Rev. Immunol. 2020, 38, 147– 170, DOI: 10.1146/annurev-immunol-071219-125715Google Scholar307https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXotVGntrk%253D&md5=c59095f280dd378b705afa9b15380a35Microbiota Metabolites in Health and DiseaseMcCarville, Justin L.; Chen, Grischa Y.; Cuevas, Victor D.; Troha, Katia; Ayres, Janelle S.Annual Review of Immunology (2020), 38 (), 147-170CODEN: ARIMDU; ISSN:0732-0582. (Annual Reviews)A review. Metab. is one of the strongest drivers of interkingdom interactions-including those between microorganisms and their multicellular hosts. Traditionally thought to fuel energy requirements and provide building blocks for biosynthetic pathways, metab. is now appreciated for its role in providing metabolites, small-mol. intermediates generated from metabolic processes, to perform various regulatory functions to mediate symbiotic relationships between microbes and their hosts. Here, we review recent advances in our mechanistic understanding of how microbiota-derived metabolites orchestrate and support physiol. responses in the host, including immunity, inflammation, defense against infections, and metab. Understanding how microbes metabolically communicate with their hosts will provide us an opportunity to better describe how a host interacts with all microbes-beneficial, pathogenic, and commensal-and an opportunity to discover new ways to treat microbial-driven diseases.
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308Wang, Y.; Li, N.; Yang, J. J.; Zhao, D. M.; Chen, B.; Zhang, G. Q.; Chen, S.; Cao, R. F.; Yu, H.; Zhao, C. Y. Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder. Pharmacol. Res. 2020, 157, 104784, DOI: 10.1016/j.phrs.2020.104784Google Scholar308https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXptVChs7w%253D&md5=c107eaa07acc8541d964e2cf46379c73Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorderWang, Ying; Li, Ning; Yang, Jun-Jie; Zhao, Dong-Mei; Chen, Bin; Zhang, Guo-Qing; Chen, Shuo; Cao, Rui-Fang; Yu, Han; Zhao, Chang-Ying; Zhao, Lu; Ge, Yong-Sheng; Liu, Yi; Zhang, Le-Hai; Hu, Wei; Zhang, Lei; Gai, Zhong-TaoPharmacological Research (2020), 157 (), 104784CODEN: PHMREP; ISSN:1043-6618. (Elsevier Ltd.)The prevalence of autism spectrum disorders (ASD) is increasing, but its etiol. remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathol. and more human research is needed. This study was divided into two stages,. At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were obsd. at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant redn. in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metab. disorder (decreased homovanillic acid) were obsd. in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addn., our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in assocn. with improved ASD symptoms, including a hyper-serotonergic state and dopamine metab. disorder.
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309Morais, L. H.; Schreiber, H. L. t.; Mazmanian, S. K. The gut microbiota-brain axis in behaviour and brain disorders. Nat. Rev. Microbiol. 2021, 19, 241– 255, DOI: 10.1038/s41579-020-00460-0Google Scholar309https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFGqtb3O&md5=2baa4b73ccf5194f9aae45b8c6df701fThe gut microbiota-brain axis in behaviour and brain disordersMorais, Livia H.; Schreiber IV, Henry L.; Mazmanian, Sarkis K.Nature Reviews Microbiology (2021), 19 (4), 241-255CODEN: NRMACK; ISSN:1740-1526. (Nature Research)Abstr.: In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the 'gut-brain axis'. These processes may affect human health, as certain animal behaviors appear to correlate with the compn. of gut bacteria, and disruptions in microbial communities have been implicated in several neurol. disorders. Most insights about host-microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biol. systems, and possible contributions by the gut microbiota to neurol. disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health.
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310Cani, P. D.; Amar, J.; Iglesias, M. A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A. M.; Fava, F.; Tuohy, K. M.; Chabo, C. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56, 1761– 1772, DOI: 10.2337/db06-1491Google Scholar310https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXnvVWjurk%253D&md5=0021ad14696d8ef622651cded925b58eMetabolic endotoxemia initiates obesity and insulin resistanceCani, Patrice D.; Amar, Jacques; Iglesias, Miguel Angel; Poggi, Marjorie; Knauf, Claude; Bastelica, Delphine; Neyrinck, Audrey M.; Fava, Francesca; Tuohy, Kieran M.; Chabo, Chantal; Waget, Aurelie; Delmee, Evelyne; Cousin, Beatrice; Sulpice, Thierry; Chamontin, Bernard; Ferrieres, Jean; Tanti, Jean-Francois; Gibson, Glenn R.; Casteilla, Louis; Delzenne, Nathalie M.; Alessi, Marie Christine; Burcelin, RemyDiabetes (2007), 56 (7), 1761-1772CODEN: DIAEAZ; ISSN:0012-1797. (American Diabetes Association)Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, resp., on a nutritional basis and that a 4-wk high-fat diet chronically increased plasma LPS concn. two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-contg. microbiota in the gut. When metabolic endotoxemia was induced for 4 wk in mice through continuous s.c. infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue wt. gain were increased to a similar extent as in high-fat-fed mice. In addn., adipose tissue F4/80-pos. cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body wt. gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concn. could be a potent strategy for the control of metabolic diseases.
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311Serino, M.; Luche, E.; Gres, S.; Baylac, A.; Bergé, M.; Cenac, C.; Waget, A.; Klopp, P.; Iacovoni, J.; Klopp, C. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 2012, 61, 543– 553, DOI: 10.1136/gutjnl-2011-301012Google Scholar311https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmsFOis70%253D&md5=5cf617bd75501023775b64d89f1677a7Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiotaSerino, Matteo; Luche, Elodie; Gres, Sandra; Baylac, Audrey; Berge, Mathieu; Cenac, Claire; Waget, Aurelie; Klopp, Pascale; Iacovoni, Jason; Klopp, Christophe; Mariette, Jerome; Bouchez, Olivier; Lluch, Jerome; Ouarne, Francoise; Monsan, Pierre; Valet, Philippe; Roques, Christine; Amar, Jacques; Bouloumie, Anne; Theodorou, Vassilia; Burcelin, RemyGut (2012), 61 (4), 543-553CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. Methods The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an addnl. group of mice was given a glucooligosaccharide (GOS)-supplemented HFD (HFD+GOS). Results Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was assocd. with increased gut permeability linked to increased endotoxemia and to a dramatic increase in cell no. in the stroma vascular fraction from visceral white adipose tissue. Most of the physiol. characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibers. Conclusions The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.
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312Ostojic, S. M. Inadequate Production of H(2) by Gut Microbiota and Parkinson Disease. Trends Endocrinol Metab 2018, 29, 286– 288, DOI: 10.1016/j.tem.2018.02.006Google Scholar312https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXivVCku7Y%253D&md5=eb96ab049fcf5d094e14786a4e627731Inadequate Production of H2 by Gut Microbiota and Parkinson DiseaseOstojic, Sergej M.Trends in Endocrinology and Metabolism (2018), 29 (5), 286-288CODEN: TENME4; ISSN:1043-2760. (Elsevier Ltd.)A review. Dysbiosis of the gut flora accompanies Parkinson disease (PD), yet no specific cause-effect link has been identified so far. The gut microbiota produce mol. hydrogen (H2), a ubiquitous mol. recently recognized as a biol. active gas with antioxidant, antiapoptotic, anti-inflammatory, cytoprotective, and signaling properties. Here, we discuss an idea that an impaired prodn. of endogenous H2 by intestinal microbiota might play a role in PD pathogenesis, with supplemental H2 debated as a possible therapy for this progressive neurodegenerative disease.
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313Kalantar-Zadeh, K.; Berean, K. J.; Burgell, R. E.; Muir, J. G.; Gibson, P. R. Intestinal gases: influence on gut disorders and the role of dietary manipulations. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 733– 747, DOI: 10.1038/s41575-019-0193-zGoogle Scholar313https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvVShurnN&md5=8897dbad5ca2972fdfb292a4ebba4ccbIntestinal gases: influence on gut disorders and the role of dietary manipulationsKalantar-Zadeh, Kourosh; Berean, Kyle J.; Burgell, Rebecca E.; Muir, Jane G.; Gibson, Peter R.Nature Reviews Gastroenterology & Hepatology (2019), 16 (12), 733-747CODEN: NRGHA9; ISSN:1759-5045. (Nature Research)A review. The inner workings of the intestines, in which the body and microbiome intersect to influence gut function and systemic health, remain elusive. Carbon dioxide, hydrogen, methane and hydrogen sulfide, as well as a variety of trace gases, are generated by the chem. interactions and microbiota within the gut. Profiling of these intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. Indeed, different tools for measuring these intestinal gases have been developed, including newly developed gas-sensing capsule technol. Gases can, according to their type, concn. and vol., induce or relieve abdominal symptoms, and might also have physiol., pathogenic and therapeutic effects. Thus, profiling and modulating intestinal gases could be powerful tools for disease prevention and/or therapy. As the interactions between the microbiota, chem. constituents and fermentative substrates of the gut are principally influenced by dietary intake, altering the diet, which, in turn, changes gas profiles, is the main therapeutic approach for gastrointestinal disorders. An improved understanding of the complex interactions within the intestines that generate gases will enhance our ability to prevent, diagnose, treat and monitor many gastrointestinal disorders.
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314Pacher, P.; Beckman, J. S.; Liaudet, L. Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 2007, 87, 315– 424, DOI: 10.1152/physrev.00029.2006Google Scholar314https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXitVagsr8%253D&md5=43534aa55fe52c09a2c19d04e8a652ddNitric oxide and peroxynitrite in health and diseasePacher, Pal; Beckman, Joseph S.; Liaudet, LucasPhysiological Reviews (2007), 87 (1), 315-424CODEN: PHREA7; ISSN:0031-9333. (American Physiological Society)A review. The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biol. and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every crit. cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacol. strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.
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315Singh, S. B.; Lin, H. C. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms 2015, 3, 866– 889, DOI: 10.3390/microorganisms3040866Google Scholar315https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXltFCht7s%253D&md5=4a8fd11434a2cff9c586ba62d5e68c59Hydrogen sulfide in physiology and diseases of the digestive tractSingh, Sudha B.; Lin, Henry C.Microorganisms (2015), 3 (4), 866-889CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Hydrogen sulfide (H2S) is a Janus-faced mol. On one hand, several toxic functions have been attributed to H2S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H2S delivery based clin. therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H2S has been found to have pleiotropic effects on physiol. and health. H2S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addn. to H2S prodn. by mammalian cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), H2S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate redn. (DSR) pathway. In the gut, H2S regulates functions such as inflammation, ischemia/reperfusion injury and motility. H2S derived from gut microbes has been found to be assocd. with gastrointestinal disorders such as ulcerative colitis, Crohn's disease and irritable bowel syndrome. This underscores the importance of gut microbes and their prodn. of H2S on host physiol. and pathophysiol.
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316Sen, N. Functional and Molecular Insights of Hydrogen Sulfide Signaling and Protein Sulfhydration. J. Mol. Biol. 2017, 429, 543– 561, DOI: 10.1016/j.jmb.2016.12.015Google Scholar316https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitFGhsbvI&md5=4845c8ac79246a01df007496188e982dFunctional and Molecular Insights of Hydrogen Sulfide Signaling and Protein SulfhydrationSen, NilkanthaJournal of Molecular Biology (2017), 429 (4), 543-561CODEN: JMOBAK; ISSN:0022-2836. (Elsevier Ltd.)A review. Hydrogen sulfide (H2S), a novel gasotransmitter, is endogenously synthesized by multiple enzymes that are differentially expressed in the peripheral tissues and central nervous systems. H2S regulates a wide range of physiol. processes, namely cardiovascular, neuronal, immune, respiratory, gastrointestinal, liver, and endocrine systems, by influencing cellular signaling pathways and sulfhydration of target proteins. This review focuses on the recent progress made in H2S signaling that affects mechanistic and functional aspects of several biol. processes such as autophagy, inflammation, proliferation and differentiation of stem cell, cell survival/death, and cellular metab. under both physiol. and pathol. conditions. Moreover, we highlighted the cross-talk between nitric oxide and H2S in several biol. contexts.
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317Skonieczna-Żydecka, K.; Marlicz, W.; Misera, A.; Koulaouzidis, A.; Łoniewski, I. Microbiome─The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health. Journal of Clinical Medicine 2018, 7, 521, DOI: 10.3390/jcm7120521Google ScholarThere is no corresponding record for this reference.
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318Schmulson, M. J.; Drossman, D. A. What Is New in Rome IV. J. Neurogastroenterol. Motil. 2017, 23, 151– 163, DOI: 10.5056/jnm16214Google Scholar318https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czkt1Kmug%253D%253D&md5=ef944cf8294c397a77f10dbb49e81a12What Is New in Rome IVSchmulson Max J; Drossman Douglas A; Drossman Douglas AJournal of neurogastroenterology and motility (2017), 23 (2), 151-163 ISSN:2093-0879.Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the Rome criteria; the criteria may change over time as new scientific data emerge. The Rome IV was released in May 2016. The aim is to review the main changes in Rome IV. FGIDs are now called disorders of gut-brain interaction (DGBI). Rome IV has a multicultural rather than a Western-culture focus. There are new chapters including multicultural, age-gender-women's health, intestinal microenvironment, biopsychosocial, and centrally mediated disorders. New disorders have been included although not truly FGIDs, but fit the new definition of DGBI including opioid-induced gastrointestinal hyperalgesia , opioid-induced constipation , and cannabinoid hyperemesis . Also, new FGIDs based on available evidence including reflux hypersensitivity and centrally mediated abdominal pain syndrome . Using a normative survey to determine the frequency of normal bowel symptoms in the general population changes in the time frame for diagnosis were introduced. For irritable bowel syndrome (IBS) only pain is required and discomfort was eliminated because it is non-specific, having different meanings in different languages. Pain is now related to bowel movements rather than just improving with bowel movements (ie, can get worse with bowel movement). Functional bowel disorders (functional diarrhea , functional constipation , IBS with predominant diarrhea [IBS-D], IBS with predominant constipation [IBS-C ], and IBS with mixed bowel habits ) are considered to be on a continuum rather than as independent entities. Clinical applications such as diagnostic algorithms and the Multidimensional Clinical Profile have been updated. The new Rome IV iteration is evidence-based, multicultural oriented and with clinical applications. As new evidence become available, future updates are expected.
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319Stasi, C.; Nisita, C.; Cortopassi, S.; Corretti, G.; Gambaccini, D.; De Bortoli, N.; Fani, B.; Simonetti, N.; Ricchiuti, A.; Dell’Osso, L. Subthreshold Psychiatric Psychopathology in Functional Gastrointestinal Disorders: Can It Be the Bridge between Gastroenterology and Psychiatry?. Gastroenterol. Res. Pract. 2017, 2017, 1953435, DOI: 10.1155/2017/1953435Google Scholar319https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M3oslGisA%253D%253D&md5=ab67afe646cf40eb0c1e04990e44d0adSubthreshold Psychiatric Psychopathology in Functional Gastrointestinal Disorders: Can It Be the Bridge between Gastroenterology and Psychiatry?Stasi Cristina; Nisita Cristiana; Cortopassi Sonia; Dell'Osso Liliana; Corretti Giorgio; Gambaccini Dario; De Bortoli Nicola; Fani Bernardo; Simonetti Natalia; Ricchiuti Angelo; Marchi Santino; Bellini MassimoGastroenterology research and practice (2017), 2017 (), 1953435 ISSN:1687-6121.BACKGROUND AND AIMS: Functional gastrointestinal disorders (FGDs) are multifactorial disorders of the gut-brain interaction. This study investigated the prevalence of Axis I and spectrum disorders in patients with FGD and established the link between FGDs and psychopathological dimensions. METHODS: A total of 135 consecutive patients with FGD were enrolled. The symptoms' severity was evaluated using questionnaires, while the psychiatric evaluation by clinical interviews established the presence/absence of mental (Diagnostic and Statistical Manual-4th edition, Axis I Diagnosis) or spectrum disorders. RESULTS: Of the 135 patients, 42 (32.3%) had functional dyspepsia, 52 (40.0%) had irritable bowel syndrome, 21 (16.2%) had functional bloating, and 20 (15.4%) had functional constipation. At least one psychiatric disorder was present in 46.9% of the patients, while a suprathreshold panic spectrum was present in 26.2%. Functional constipation was associated with depressive disorders (p < 0.05), while functional dyspepsia was related to the current major depressive episode (p < 0.05). Obsessive-compulsive spectrum was correlated with the presence of functional constipation and irritable bowel syndrome (p < 0.05). CONCLUSION: The high prevalence of subthreshold psychiatric symptomatology in patients with FGD, which is likely to influence the expression of gastrointestinal symptoms, suggested the usefulness of psychological evaluation in patients with FGDs.
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320Cryan, J. F.; O’Riordan, K. J.; Cowan, C. S. M.; Sandhu, K. V.; Bastiaanssen, T. F. S.; Boehme, M.; Codagnone, M. G.; Cussotto, S.; Fulling, C.; Golubeva, A. V. The Microbiota-Gut-Brain Axis. Physiol. Rev. 2019, 99, 1877– 2013, DOI: 10.1152/physrev.00018.2018Google Scholar320https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFWjsLs%253D&md5=efad6ac39777a0569fa724115a775361The microbiota-gut-brain axisCryan, John F.; O'Riordan, Kenneth J.; Cowan, Caitlin S. M.; Sandhu, Kiran V.; Bastiaanssen, Thomaz F. S.; Boehme, Marcus; Codagnone, Martin G.; Cussotto, Sofia; Fulling, Christine; Golubeva, Anna V.; Guzzetta, Katherine E.; Jaggar, Minal; Long-Smith, Caitriona M.; Lyte, Joshua M.; Martin, Jason A.; Molinero-Perez, Alicia; Moloney, Gerard; Morelli, Emanuela; Morillas, Enrique; O'Connor, Rory; Cruz-Pereira, Joana S.; Peterson, Veronica L.; Rea, Kieran; Ritz, Nathaniel L.; Sherwin, Eoin; Spichak, Simon; Teichman, Emily M.; van de Wouw, Marcel; Ventura-Silva, Ana Paula; Wallace-Fitzsimons, Shauna E.; Hyland, Niall; Clarke, Gerard; Dinan, Timothy G.Physiological Reviews (2019), 99 (4), 1877-2013CODEN: PHREA7; ISSN:1522-1210. (American Physiological Society)A review. The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biol. and physiol. basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metab., the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota compn. in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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321Gralnek, I. M.; Hays, R. D.; Kilbourne, A.; Naliboff, B.; Mayer, E. A. The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology 2000, 119, 654– 660, DOI: 10.1053/gast.2000.16484Google Scholar321https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3cvnt1amuw%253D%253D&md5=61ae873d02ae9f3dc2ea36f59b8b0b4bThe impact of irritable bowel syndrome on health-related quality of lifeGralnek I M; Hays R D; Kilbourne A; Naliboff B; Mayer E AGastroenterology (2000), 119 (3), 654-60 ISSN:0016-5085.BACKGROUND & AIMS: Few data are available to evaluate health-related quality of life (HRQOL) of people with irritable bowel syndrome (IBS). We evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the U.S. general population and for people with selected chronic diseases. METHODS: Using the SF-36 Health Survey, we compared the HRQOL of IBS patients (n = 877) with previously reported SF-36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end-stage renal disease (ESRD). RESULTS: On all 8 SF-36 scales, IBS patients had significantly worse HRQOL than the U.S. general population (P < 0. 001). Compared with GERD patients, IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF-36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF-36 scale scores than patients with depression (P < 0.001). CONCLUSIONS: IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy/fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. These data offer further insight into the impact of IBS on patient functional status and well-being.
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322O’Keeffe, M.; Lomer, M. C. Who should deliver the low FODMAP diet and what educational methods are optimal: a review. J. Gastroenterol. Hepatol. 2017, 32, 23– 26, DOI: 10.1111/jgh.13690Google Scholar322https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czhtlamug%253D%253D&md5=b20c62bcfe40e3459a5f44a9f3823f2fWho should deliver the low FODMAP diet and what educational methods are optimal: a reviewO'Keeffe Majella; Lomer Miranda Ce; Lomer Miranda CeJournal of gastroenterology and hepatology (2017), 32 Suppl 1 (), 23-26 ISSN:.Dietary management is being hailed as an effective strategy for the management of irritable bowel syndrome. Specifically, a diet low in fermentable carbohydrates (FODMAPs) has demonstrated efficacy in approximately 70% of patients. As evidence in support of the low FODMAP diet continues to emerge, there is increasing debate regarding implementation of the diet particularly concerning who should educate patients and how to educate them. Registered dieticians have largely pioneered the evidence that supports the effectiveness of the low FODMAP diet in irritable bowel syndrome, and the diet is recognized as a dietician-led therapy. However, there is an increasing trend for non-dietician-led implementation of the diet despite an absence of evidence on both the clinical or cost-effectiveness of such. Additionally, there is a growing requirement for dietetic services to increase capacity in response to increasing referrals, and consequently, there is a need to investigate innovative ways to educate patients whilst maintaining dietician-led intervention. Herein, we review the evidence for delivery of the low FODMAP diet and discuss potentially effective methods for service delivery.
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323Koloski, N. A.; Jones, M.; Talley, N. J. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study. Alimentary pharmacology & therapeutics 2016, 44, 592– 600, DOI: 10.1111/apt.13738Google ScholarThere is no corresponding record for this reference.
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324Eijsbouts, C.; Zheng, T.; Kennedy, N. A.; Bonfiglio, F.; Anderson, C. A.; Moutsianas, L.; Holliday, J.; Shi, J.; Shringarpure, S.; Agee, M. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat. Genet. 2021, 53, 1543– 1552, DOI: 10.1038/s41588-021-00950-8Google Scholar324https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVehtb7F&md5=84ea904f4564f6c663d42d80481f2018Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disordersEijsbouts, Chris; Zheng, Tenghao; Kennedy, Nicholas A.; Bonfiglio, Ferdinando; Anderson, Carl A.; Moutsianas, Loukas; Holliday, Joanne; Shi, Jingchunzi; Shringarpure, Suyash; Voda, Alexandru-Ioan; Farrugia, Gianrico; Franke, Andre; Hubenthal, Matthias; Abecasis, Goncalo; Zawistowski, Matthew; Skogholt, Anne Heidi; Ness-Jensen, Eivind; Hveem, Kristian; Esko, Tonu; Teder-Laving, Maris; Zhernakova, Alexandra; Camilleri, Michael; Boeckxstaens, Guy; Whorwell, Peter J.; Spiller, Robin; McVean, Gil; D'Amato, Mauro; Jostins, Luke; Parkes, MilesNature Genetics (2021), 53 (11), 1543-1552CODEN: NGENEC; ISSN:1061-4036. (Nature Portfolio)Irritable bowel syndrome (IBS) results from disordered brain-gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiol. mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide assocn. study with 53,400 cases and 433,201 controls and replicated significant assocns. in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are assocd. with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Addnl. analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain-gut interactions underlying IBS.
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325Schwarz, E.; Maukonen, J.; Hyytiäinen, T.; Kieseppä, T.; Orešič, M.; Sabunciyan, S.; Mantere, O.; Saarela, M.; Yolken, R.; Suvisaari, J. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr. Res. 2018, 192, 398– 403, DOI: 10.1016/j.schres.2017.04.017Google Scholar325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1crhtV2itw%253D%253D&md5=3768583481e3c898421edc538da930d1Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment responseSchwarz Emanuel; Maukonen Johanna; Hyytiainen Tiina; Saarela Maria; Kieseppa Tuula; Oresic Matej; Sabunciyan Sarven; Yolken Robert; Mantere Outi; Suvisaari JaanaSchizophrenia research (2018), 192 (), 398-403 ISSN:.The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission.
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326Castro-Nallar, E.; Bendall, M. L.; Pérez-Losada, M.; Sabuncyan, S.; Severance, E. G.; Dickerson, F. B.; Schroeder, J. R.; Yolken, R. H.; Crandall, K. A. Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls. PeerJ. 2015, 3, e1140, DOI: 10.7717/peerj.1140Google ScholarThere is no corresponding record for this reference.
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327Belkaid, Y.; Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 2014, 157, 121– 141, DOI: 10.1016/j.cell.2014.03.011Google Scholar327https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtVCqsL8%253D&md5=8a9f60a467ebbefb7dba7fde7e46f423Role of the Microbiota in Immunity and InflammationBelkaid, Yasmine; Hand, Timothy W.Cell (Cambridge, MA, United States) (2014), 157 (1), 121-141CODEN: CELLB5; ISSN:0092-8674. (Cell Press)A review. The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relation of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where the authors' symbiotic relation with the microbiota has been the most affected.
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328Anderson, G.; Maes, M. Bipolar disorder: role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolites. Curr. Psychiatry Rep 2015, 17, 8, DOI: 10.1007/s11920-014-0541-1Google Scholar328https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MvpslSjtg%253D%253D&md5=2a5eee380a11b5e55ca19099ab9cdb93Bipolar disorder: role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolitesAnderson George; Maes MichaelCurrent psychiatry reports (2015), 17 (2), 8 ISSN:.Bipolar disorder (BD) is a complex disorder with a range of presentations. BD is defined by the presentation of symptoms of mania or depression, with classification dependent on patient/family reports and behavioural observations. Recent work has investigated the biological underpinnings of BD, highlighting the role played by increased immune-inflammatory activity, which is readily indicated by changes in pro-inflammatory cytokines or signalling, both centrally and systemically, e.g. increased interleukin-6 trans-signalling. Here, we review the recent data on immune-inflammatory pathways and cytokine changes in BD. Such changes are intimately linked to changes in oxidative and nitrosative stress (O&NS) and neuroregulatory tryptophan catabolites (TRYCATs), both centrally and peripherally. TRYCATs take tryptophan away from serotonin, N-acetylserotonin and melatonin synthesis, driving it down the TRYCAT pathway, predominantly as a result of the pro-inflammatory cytokine induction of indoleamine 2,3-dioxygenase. This has led to an emerging biological perspective on the aetiology, course and treatment of BD. Such data also better integrates the numerous comorbidities associated with BD, including addiction, cardiovascular disorders and increased reporting of pain. Immune-inflammatory, O&NS and TRYCAT pathways are also likely to be relevant biological underpinnings to the significant decrease in life expectancy in BD.
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329Clarke, G.; Fitzgerald, P.; Cryan, J. F.; Cassidy, E. M.; Quigley, E. M.; Dinan, T. G. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. BMC Gastroenterol. 2009, 9, 6, DOI: 10.1186/1471-230X-9-6Google Scholar329https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M7mvVyktA%253D%253D&md5=e1e82fee8d56c114872bfc68605d15c2Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohortClarke Gerard; Fitzgerald Peter; Cryan John F; Cassidy Eugene M; Quigley Eamonn M; Dinan Timothy GBMC gastroenterology (2009), 9 (), 6 ISSN:.BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that affects 10-15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26). METHODS: Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay. RESULTS: Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio. CONCLUSION: These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.
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330Clarke, G.; McKernan, D.; Gaszner, G.; Quigley, E.; Cryan, J.; Dinan, T. A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome. Front. Pharmacol. 2012, 3, 90, DOI: 10.3389/fphar.2012.00090Google Scholar330https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmsVKqsbs%253D&md5=a8bf82d079221b6140978215a07b42a8A distinct profile of tryptophan metabolism along the kynurenine pathway downstream of toll-like receptor activation in irritable bowel syndromeClarke, Gerard; McKernan, Declan P.; Gaszner, Gabor; Quigley, Eamonn M.; Cryan, John F.; Dinan, Timothy G.Frontiers in Gastrointestinal Pharmacology (2012), 3 (May), 90CODEN: FGPRAL ISSN:. (Frontiers Media S.A.)Irritable bowel syndrome (IBS), a disorder of the brain-gut axis, is characterised by the absence of reliable biol. markers. Tryptophan is an essential amino acid that serves as a precursor to serotonin but which can alternatively be metabolised along the kynurenine pathway leading to the prodn. of other neuroactive agents. We previously reported an increased degrdn. of tryptophan along this immunoresponsive pathway in IBS. Recently, altered cytokine prodn. following activation of specific members of the toll-like receptor (TLR) family (TLR1-9) has also been demonstrated in IBS. However, the relationship between TLR activation and kynurenine pathway activity in IBS is unknown. In this study, we investigated whether activation of specific TLRs elicits exaggerated kynurenine prodn. in IBS patients compared to controls. Whole blood from IBS patients and healthy controls was cultured with a panel of nine different TLR agonists for 24 h. Cell culture supernatants were then analyzed for both tryptophan and kynurenine concns., as were plasma samples from both cohorts. IBS subjects had an elevated plasma kynurenine:tryptophan ratio compared to healthy controls. Furthermore, we demonstrated a differential downstream profile of kynurenine prodn. subsequent to TLR activation in IBS patients compared to healthy controls. This profile included alterations at TLR1/2, TLR2, TLR3, TLR5, TLR7, and TLR8. Our data expands on our previous understanding of altered tryptophan metab. in IBS and suggests that measurement of tryptophan metabolites downstream of TLR activation may ultimately find utility as components of a biomarker panel to aid gastroenterologists in the diagnosis of IBS. Furthermore, these studies implicate the modulation of TLRs as means through which aberrant tryptophan metab. along the kynurenine pathway can be controlled, a novel potential therapeutic strategy in this and other disorders.
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331Liang, X.; FitzGerald, G. A. Timing the Microbes: The Circadian Rhythm of the Gut Microbiome. J. Biol. Rhythms 2017, 32, 505– 515, DOI: 10.1177/0748730417729066Google Scholar331https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXislSrsLo%253D&md5=58f6fe2c84152d919b7b75b41bd2b34eTiming the microbes: the circadian rhythm of the gut microbiomeLiang, Xue; FitzGeraldt, Garret A.Journal of Biological Rhythms (2017), 32 (6), 505-515CODEN: JBRHEE; ISSN:0748-7304. (Sage Publications)A review. The mammalian circadian clock system, which includes the master clock and peripheral clocks, times different biol. processes in reaction to external cues, such as the light-dark cycle. However, the chronobiol. of pro- karyotic cells is less well understood, except for in cyanobacteria. The recent blooming of gut microbiome research has revealed a crit. role for the trillions of microbes residing in the vertebrate gut in detg. both health and dis- ease in the host. The question of whether the gut microbiome exhibits circadian oscillation and how it synchronizes with the host circadian clock has attracted considerable interest. In this review, we discuss the time-of-day-dependent compositional and functional structure within the gut microbial community, how it is regulated by the host, and how it reciprocally influences the host cir- cadian dock.
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332Enck, P.; Aziz, Q.; Barbara, G.; Farmer, A. D.; Fukudo, S.; Mayer, E. A.; Niesler, B.; Quigley, E. M.; Rajilić-Stojanović, M.; Schemann, M. Irritable bowel syndrome. Nat. Rev. Dis Primers 2016, 2, 16014, DOI: 10.1038/nrdp.2016.14Google Scholar332https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28botVWqtg%253D%253D&md5=177e4e06ce4142c039bfd8937b08683fIrritable bowel syndromeEnck Paul; Schwille-Kiuntke Juliane; Zipfel Stephan; Aziz Qasim; Farmer Adam D; Barbara Giovanni; Fukudo Shin; Mayer Emeran A; Niesler Beate; Quigley Eamonn M M; Rajilic-Stojanovic Mirjana; Schemann Michael; Simren Magnus; Spiller Robin CNature reviews. Disease primers (2016), 2 (), 16014 ISSN:.Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain-gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.
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333Dalile, B.; Vervliet, B.; Bergonzelli, G.; Verbeke, K.; Van Oudenhove, L. Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trial. Neuropsychopharmacology 2020, 45, 2257– 2266, DOI: 10.1038/s41386-020-0732-xGoogle Scholar333https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFKgtLzM&md5=d8a5d4b71e49c7a313eea32e4dfb6bd0Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trialDalile, Boushra; Vervliet, Bram; Bergonzelli, Gabriela; Verbeke, Kristin; Van Oudenhove, LukasNeuropsychopharmacology (2020), 45 (13), 2257-2266CODEN: NEROEW; ISSN:0893-133X. (Nature Research)Short-chain fatty acids (SCFAs) are products of microbial fermn. of dietary fiber in the colon and may mediate microbiota-gut-brain communication. However, their role in modulating psychobiol. processes that underlie the development of stress- and anxiety-related disorders is not mechanistically studied in humans. In this triple-blind, randomized, placebo-controlled intervention trial, we examine in a parallel group design the effects of 1-wk colonic SCFA-mixt. delivery in doses equiv. to fermn. of 10 g or 20 g of arabinoxylan oligosaccharides on responses to psychosocial stress and fear tasks in 66 healthy men. We demonstrate that low and high doses of SCFAs significantly attenuate the cortisol response to psychosocial stress compared to placebo. Both doses of SCFAs increase serum SCFA levels and this increase in circulating SCFAs co-varies significantly with the attenuation of the cortisol response to psychosocial stress. Colonic SCFA delivery does not modulate fecal SCFA concns., serum brain-derived neurotrophic factor, cortisol awakening response, fear learning and extinction, or subjective mood ratings. These results demonstrate that colon-delivered SCFAs modulate hypothalamic-pituitary-adrenal axis reactivity to psychosocial stress, thereby supporting their hypothesized role in microbiota-gut-brain communication.
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334Bercik, P.; Park, A. J.; Sinclair, D.; Khoshdel, A.; Lu, J.; Huang, X.; Deng, Y.; Blennerhassett, P. A.; Fahnestock, M.; Moine, D. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol. Motil. 2011, 23, 1132– 1139, DOI: 10.1111/j.1365-2982.2011.01796.xGoogle Scholar334https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xns1Kmuw%253D%253D&md5=9b3305bf4a6c9e6627db3e1dafdba5d3The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communicationBercik, P.; Park, A. J.; Sinclair, D.; Khoshdel, A.; Lu, I.; Huang, X.; Deng, Y.; Blennerhassett, P. A.; Fahnestock, M.; Moine, D.; Berger, B.; Huizinga, J. D.; Kunze, W.; McLean, P. G.; Bergonzelli, G. E.; Collins, S. M.; Verdu, E. F.Neurogastroenterology & Motility (2011), 23 (12), 1132-1139CODEN: NMOTEK; ISSN:1350-1925. (Wiley-Blackwell)The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chem. colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-wk cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histol. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was assocd. with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histol. scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. & Inferences In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or prodn. of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.
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335Mishima, Y.; Ishihara, S. Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome. Int. J. Mol. Sci. 2020, 21, 8664, DOI: 10.3390/ijms21228664Google Scholar335https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFyhtb3L&md5=0b6b935b69b2563c790e931794404bd4Molecular mechanisms of microbiota-mediated pathology in irritable bowel syndromeMishima, Yoshiyuki; Ishihara, ShunjiInternational Journal of Molecular Sciences (2020), 21 (22), 8664CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)A review. Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders, and accumulating evidence gained in both preclin. and clin. studies indicate the involvement of enteric microbiota in its pathogenesis. Gut resident microbiota appear to influence brain activity through the enteric nervous system, while their compn. and function are affected by the central nervous system. Based on these results, the term "brain-gut-microbiome" has been proposed and enteric microbiota have become a potential therapeutic target in IBS cases. However, details regarding the microbe-related pathophysiol. of IBS remain elusive. This review summarizes the existing knowledge of mol. mechanisms in the pathogenesis of IBS as well as recent progress related to microbiome-derived neurotransmitters, compds., metabolites, neuroendocrine factors, and enzymes.
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336Leeming, E. R.; Johnson, A. J.; Spector, T. D.; Le Roy, C. I. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients 2019, 11, 2862, DOI: 10.3390/nu11122862Google ScholarThere is no corresponding record for this reference.
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337Hillestad, E. M. R.; van der Meeren, A.; Nagaraja, B. H.; Bjo̷rsvik, B. R.; Haleem, N.; Benitez-Paez, A.; Sanz, Y.; Hausken, T.; Lied, G. A.; Lundervold, A. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J. Gastroenterol. 2022, 28, 412– 431, DOI: 10.3748/wjg.v28.i4.412Google Scholar337https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XlvFalsL8%253D&md5=1035ffb12c3a336ddf4b65e4a1c0e462Gut bless you: the microbiota-gut-brain axis in irritable bowel syndromeHillestad, Eline Margrete Randulff; van der Meeren, Aina; Nagaraja, Bharat Halandur; Bjoersvik, Ben Rene; Haleem, Noman; Benitez-Paez, Alfonso; Sanz, Yolanda; Hausken, Trygve; Lied, Gulen Arslan; Lundervold, Arvid; Berentsen, BirgitteWorld Journal of Gastroenterology (2022), 28 (4), 412-431CODEN: WJGAF2; ISSN:2219-2840. (Baishideng Publishing Group Inc.)A review. Irritable bowel syndrome (IBS) is a common clin. label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiol. of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiol. mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiol., or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing. In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clin. microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data anal. in IBS.
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338Hugerth, L. W.; Andreasson, A.; Talley, N. J.; Forsberg, A. M.; Kjellström, L.; Schmidt, P. T.; Agreus, L.; Engstrand, L. No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population. Gut 2020, 69, 1076– 1084, DOI: 10.1136/gutjnl-2019-318717Google Scholar338https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mnmslymtg%253D%253D&md5=55d809f6c060f0fa2ddfb314d2fed1bcNo distinct microbiome signature of irritable bowel syndrome found in a Swedish random populationHugerth Luisa W; Engstrand Lars; Andreasson Anna; Andreasson Anna; Forsberg Anna M; Schmidt Peter Thelin; Andreasson Anna; Talley Nicholas J; Kjellstrom Lars; Agreus Lars; Engstrand LarsGut (2020), 69 (6), 1076-1084 ISSN:.OBJECTIVE: The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings. DESIGN: The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases). RESULTS: While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R2=0.255, p<3E-11) as was diversity (R2=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals. CONCLUSIONS: No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.
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339Sundin, J.; Aziz, I.; Nordlander, S.; Polster, A.; Hu, Y. O. O.; Hugerth, L. W.; Pennhag, A. A. L.; Engstrand, L.; Törnblom, H.; Simrén, M. Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci. Rep. 2020, 10, 593, DOI: 10.1038/s41598-020-57468-yGoogle Scholar339https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjsVSit7w%253D&md5=fc60c1f852982038171c0216d22c5db3Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel SyndromeSundin, Johanna; Aziz, Imran; Nordlander, Sofia; Polster, Annikka; Hu, Yue O. O.; Hugerth, Luisa W.; Pennhag, Alexandra A. L.; Engstrand, Lars; Toernblom, Hans; Simren, Magnus; Oehman, LenaScientific Reports (2020), 10 (1), 593CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: Altered bacterial compn. and small intestinal bacterial overgrowth (SIBO) may be assocd. with irritable bowel syndrome (IBS). This study aimed to det. the fecal and mucosa-assocd. bacterial compn. along the gastrointestinal (GI) tract and to assess SIBO in IBS. Bacterial compn. of feces, and mucosa of the duodenum and sigmoid colon was detd. by 16S rRNA-amplicon-sequencing. SIBO was evaluated by bacterial culture of duodenal aspirate, glucose and lactulose breath tests. Mucosal antibacterial gene expression was assessed by PCR Array. The bacterial profiles of feces and the mucosa of sigmoid colon, but not duodenum, differed between IBS patients (n = 17) and HS (n = 20). The IBS specific bacterial profiles were linked to the colonic antibacterial gene expression. Fecal bacterial profile differed between IBS subtypes, while the mucosa-assocd. bacterial profile was assocd. with IBS symptom severity and breath tests results at baseline (H2 and/or CH4 ≥ 15 ppm). The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial compn. of the sigmoid colon of IBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-assocd. bacterial compn., there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS.
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340Mayer, E. A.; Labus, J.; Aziz, Q.; Tracey, I.; Kilpatrick, L.; Elsenbruch, S.; Schweinhardt, P.; Van Oudenhove, L.; Borsook, D. Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report. Gut 2019, 68, 1701– 1715, DOI: 10.1136/gutjnl-2019-318308Google Scholar340https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVCnu73M&md5=79fed8428d6c74a501436d1f274842daRole of brain imaging in disorders of brain-gut interaction: a Rome Working Team ReportMayer, Emeran A.; Labus, Jennifer; Aziz, Qasim; Tracey, Irene; Kilpatrick, Lisa; Elsenbruch, Sigrid; Schweinhardt, Petra; Van Oudenhove, Lukas; Borsook, DavidGut (2019), 68 (9), 1701-1715CODEN: GUTTAK; ISSN:0017-5749. (BMJ)A review. Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clin. symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urol. pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclin. vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
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341Seminowicz, D. A.; Labus, J. S.; Bueller, J. A.; Tillisch, K.; Naliboff, B. D.; Bushnell, M. C.; Mayer, E. A. Regional gray matter density changes in brains of patients with irritable bowel syndrome. Gastroenterology 2010, 139, 48– 57.e42, DOI: 10.1053/j.gastro.2010.03.049Google Scholar341https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cnms1yrsQ%253D%253D&md5=fa5d68d8fe3e8c5d06705f7de1162628Regional gray matter density changes in brains of patients with irritable bowel syndromeSeminowicz David A; Labus Jennifer S; Bueller Joshua A; Tillisch Kirsten; Naliboff Bruce D; Bushnell M Catherine; Mayer Emeran AGastroenterology (2010), 139 (1), 48-57.e2 ISSN:.BACKGROUND & AIMS: Several studies have examined structural brain changes associated with chronic pain syndromes, including irritable bowel syndrome (IBS), but study sample sizes have been small and heterogeneous. METHODS: We used magnetic resonance imaging-based techniques, voxel-based morphometry, and cortical thickness analysis to examine brain anatomical differences in a relatively large, tightly screened sample of IBS patients (n = 55); we compared data with that from healthy persons (controls; n = 48). RESULTS: IBS was associated with decreased gray matter density (GMD) in widespread areas of the brain, including medial prefrontal and ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum, and thalamus. Compared with controls, we observed increased GMD in patients with IBS in the pregenual anterior cingulate cortex and the orbitofrontal cortex, as well as trends in the posterior insula/secondary somatosensory cortex, (para)hippocampus, and left dorsolateral prefrontal cortex. In accounting for anxiety and depression, we found that several of the regions involved in affective processing no longer differed between patients with IBS and controls, whereas the differences in prefrontal and posterior parietal cortices remained. The areas of decreased GMD associated with IBS were largely consistent across clinical subgroups, based on predominant bowel habit and pain predominance of symptoms. No overall or regional differences were observed in cortical thickness between patients with IBS and controls. CONCLUSIONS: Changes in density of gray matter among regions involved in cognitive/evaluative functions are specifically observed in patients with IBS, whereas changes in other areas of the brain can be explained by levels of anxiety and depression.
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342Kano, M.; Grinsvall, C.; Ran, Q.; Dupont, P.; Morishita, J.; Muratsubaki, T.; Mugikura, S.; Ly, H. G.; Törnblom, H.; Ljungberg, M. Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis. Sci. Rep. 2020, 10, 11015, DOI: 10.1038/s41598-020-67048-9Google Scholar342https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlClsb3P&md5=b7f4ea6496a4628d56c6644c1b7a49a7Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysisKano, Michiko; Grinsvall, Cecilia; Ran, Qian; Dupont, Patrick; Morishita, Joe; Muratsubaki, Tomohiko; Mugikura, Shunji; Ly, Huynh Giao; Tornblom, Hans; Ljungberg, Maria; Takase, Kei; Simren, Magnus; Van Oudenhove, Lukas; Fukudo, ShinScientific Reports (2020), 10 (1), 11015CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph anal. in two independent cohorts. We used a weighted graph anal. of the adjacency matrix based on partial correlations between time series in the different regions in each subject to det. subject specific graph measures. These graph measures were normalized by values obtained in equiv. random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent assocns. between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychol. distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organization at rest may be primarily disturbed in IBS.
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343Wilder-Smith, C. H.; Schindler, D.; Lovblad, K.; Redmond, S. M.; Nirkko, A. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut 2004, 53, 1595– 1601, DOI: 10.1136/gut.2003.028514Google Scholar343https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2crhtVWrtg%253D%253D&md5=ad6253c554b04976487e1bc95bd701c6Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controlsWilder-Smith C H; Schindler D; Lovblad K; Redmond S M; Nirkko AGut (2004), 53 (11), 1595-601 ISSN:0017-5749.BACKGROUND AND AIMS: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI). PATIENTS AND METHODS: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal). RESULTS: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS-C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain. CONCLUSIONS: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.
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344Tillisch, K.; Mayer, E. A.; Labus, J. S. Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology 2011, 140, 91– 100, DOI: 10.1053/j.gastro.2010.07.053Google Scholar344https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M%252FlsVaktw%253D%253D&md5=b0b14cfd62049cb1cba0c771498616c2Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndromeTillisch Kirsten; Mayer Emeran A; Labus Jennifer SGastroenterology (2011), 140 (1), 91-100 ISSN:.BACKGROUND AND AIMS: The responsiveness of the central nervous system is altered in patients with irritable bowel syndrome (IBS). However, because of variations in experimental paradigms, analytic techniques, and reporting practices, little consensus exists on brain responses to visceral stimulation. We aimed to identify brain regions consistently activated by supraliminal rectal stimulation in IBS patients and healthy subjects (controls) by performing a quantitative meta-analysis of published studies. METHODS: Significant foci from within-group statistical parametric maps were extracted from published neuroimaging studies that employed rectal distension. Voxel-based activation likelihood estimation was applied, pooling the results and comparing them across groups. RESULTS: Across studies, there was consistent activation in regions associated with visceral afferent processing (ie, thalamus, insula, anterior midcingulate) among IBS patients and controls, but considerable differences in the extent and specific location of foci. IBS patients differed from controls in that there were more consistent activations in regions associated with emotional arousal (pregenual anterior cingulate cortex, amygdala) and activation of a midbrain cluster, a region playing a role in endogenous pain modulation. Controls showed more consistent activation of the medial and lateral prefrontal cortex. CONCLUSIONS: Patients with IBS have greater engagement of regions associated with emotional arousal and endogenous pain modulation, but similar activation of regions involved in processing of visceral afferent information. Controls have greater engagement of cognitive modulatory regions. These results support a role for central nervous system dysregulation in IBS. These findings provide specific targets for guiding development of future neuroimaging protocols to more clearly define altered brain-gut interactions in IBS.
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345Ringel, Y.; Drossman, D. A.; Leserman, J. L.; Suyenobu, B. Y.; Wilber, K.; Lin, W.; Whitehead, W. E.; Naliboff, B. D.; Berman, S.; Mayer, E. A. Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an FMRI study. Gastroenterology 2008, 134, 396– 404, DOI: 10.1053/j.gastro.2007.11.011Google Scholar345https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1c%252Fos1Sjsg%253D%253D&md5=cb28a09dc42eb9b67c0cd64119176158Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an FMRI studyRingel Yehuda; Drossman Douglas A; Leserman Jane L; Suyenobu Brandall Y; Wilber Kathy; Lin Weili; Whitehead William E; Naliboff Bruce D; Berman Steven; Mayer Emeran AGastroenterology (2008), 134 (2), 396-404 ISSN:.BACKGROUND & AIMS: Abuse history is common in irritable bowel syndrome (IBS) and is associated with greater pain reporting, psychologic distress, and poorer health outcome. These effects may be mediated by enhanced responses to aversive visceral stimuli. We investigated the effects of IBS and abuse history on pain reporting and brain activation in response to rectal distentions. METHODS: Ten female patients with IBS and 10 controls were included. Half of patients in each group reported a history of abuse. Brain functional magnetic resonance imaging (fMRI) images and pain ratings were obtained during rectal distentions. Statistical parametric mapping identified activation in subregions of the dorsal cingulate cortex and covariation with rated pain. RESULTS: (1) Distention-elicited pain correlated with anxiety and activation of the posterior (PCC) and middle (MCC) dorsal cingulate subregions. (2) Subjects with a history of abuse showed greater activation in the left MCC (P = .022; t = 5.61) and PCC (P = .033; t = 5.00) than subjects without abuse. (3) Those with IBS and abuse reported greater pain than all others (P = .004), had more activity in the left MCC (P = .021; t = 5.29) and PCC (P = .049; t = 4.81), and had less activity in the left supragenual anterior cingulate (sACC) (P = .01; t = 4.86). CONCLUSIONS: Pain ratings during rectal distention are associated with activation of dorsal cingulate regions implicated in homeostatic afferent processing, and prior abuse enhances this activation. Patients with IBS and abuse report more pain, greater MCC/PCC activation, and reduced activity of a region implicated in pain inhibition and arousal (sACC). These findings suggest a possible explanation for the clinical observation of greater pain reporting and poorer outcome in IBS patients with a history of abuse.
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346Mayer, E. A.; Bradesi, S.; Chang, L.; Spiegel, B. M.; Bueller, J. A.; Naliboff, B. D. Functional GI disorders: from animal models to drug development. Gut 2008, 57, 384– 404, DOI: 10.1136/gut.2006.101675Google Scholar346https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjs1ektr8%253D&md5=d9ae30ed1d9dd55c0dd53bea40ec2cabFunctional GI disorders: from animal models to drug developmentMayer, E. A.; Bradesi, S.; Chang, L.; Spiegel, B. M. R.; Bueller, J. A.; Naliboff, B. D.Gut (2008), 57 (3), 384-404CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)A review. Despite considerable efforts by academic researchers and by the pharmaceutical industry, the development of novel pharmacol. treatments for irritable bowel syndrome (IBS) and other functional gastrointestinal (GI) disorders has been slow and disappointing. The traditional approach to identifying and evaluating novel drugs for these symptom-based syndromes has relied on a fairly std. algorithm using animal models, exptl. medicine models and clin. trials. In the current article, the empirical basis for this process is reviewed, focusing on the utility of the assessment of visceral hypersensitivity and GI transit, in both animals and humans, as well as the predictive validity of preclin. and clin. models of IBS for identifying successful treatments for IBS symptoms and IBS-related quality of life impairment. A review of published evidence suggests that abdominal pain, defecation-related symptoms (urgency, straining) and psychol. factors all contribute to overall symptom severity and to health-related quality of life. Correlations between readouts obtained in preclin. and clin. models and resp. symptoms are small, and the ability to predict drug effectiveness for specific as well as for global IBS symptoms is limited. One possible drug development algorithm is proposed which focuses on pharmacol. imaging approaches in both preclin. and clin. models, with decreased emphasis on evaluating compds. in symptom-related animal models, and more rapid screening of promising candidate compds. in man.
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347Labus, J. S.; Osadchiy, V.; Hsiao, E. Y.; Tap, J.; Derrien, M.; Gupta, A.; Tillisch, K.; Le Nevé, B.; Grinsvall, C.; Ljungberg, M. Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis. Microbiome 2019, 7, 45, DOI: 10.1186/s40168-019-0656-zGoogle Scholar347https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cbmsl2ksQ%253D%253D&md5=0287762a085c272f8ed0dfd145b78398Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysisLabus Jennifer S; Osadchiy Vadim; Hsiao Elaine Y; Gupta Arpana; Tillisch Kirsten; Mayer Emeran A; Hsiao Elaine Y; Tap Julien; Derrien Muriel; Le Neve Boris; Grinsvall Cecilia; Ohman Lena; Tornblom Hans; Simren Magnus; Ljungberg Maria; Ohman Lena; Simren MagnusMicrobiome (2019), 7 (1), 45 ISSN:.BACKGROUND AND AIMS: Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. METHODS: We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. RESULTS: We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. CONCLUSIONS: In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.
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348Osadchiy, V.; Mayer, E. A.; Gao, K.; Labus, J. S.; Naliboff, B.; Tillisch, K.; Chang, L.; Jacobs, J. P.; Hsiao, E. Y.; Gupta, A. Analysis of brain networks and fecal metabolites reveals brain-gut alterations in premenopausal females with irritable bowel syndrome. Transl Psychiatry 2020, 10, 367, DOI: 10.1038/s41398-020-01071-2Google Scholar348https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1Ggtr%252FI&md5=5c89e838387d24a126e6b848354226c2Analysis of brain networks and fecal metabolites reveals brain-gut alterations in premenopausal females with irritable bowel syndromeOsadchiy, Vadim; Mayer, Emeran A.; Gao, Kan; Labus, Jennifer S.; Naliboff, Bruce; Tillisch, Kirsten; Chang, Lin; Jacobs, Jonathan P.; Hsiao, Elaine Y.; Gupta, ArpanaTranslational Psychiatry (2020), 10 (1), 367CODEN: TPRSCF; ISSN:2158-3188. (Nature Research)Alterations in brain-gut-microbiome (BGM) interactions have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Here, we apply a systems biol. approach, leveraging neuroimaging and fecal metabolite data, to characterize BGM interactions that are driving IBS pathophysiol. Fecal samples and resting state fMRI images were obtained from 138 female subjects (99 IBS, 39 healthy controls (HCs)). Partial least-squares discriminant anal. (PLS-DA) was conducted to explore group differences, and partial correlation anal. explored significantly changed metabolites and neuroimaging data. All correlational tests were performed controlling for age, body mass index, and diet; results are reported after FDR correction, with q < 0.05 as significant. Compared to HCs, IBS showed increased connectivity of the putamen with regions of the default mode and somatosensory networks. Metabolite pathways involved in nucleic acid and amino acid metab. differentiated the two groups. Only a subset of metabolites, primarily amino acids, were assocd. with IBS-specific brain changes, including tryptophan, glutamate, and histidine. Histidine was the only metabolite pos. assocd. with both IBS-specific alterations in brain connectivity. Our findings suggest a role for several amino acid metabolites in modulating brain function in IBS. These metabolites may alter brain connectivity directly, by crossing the blood-brain-barrier, or indirectly through peripheral mechanisms. This is the first study to integrate both neuroimaging and fecal metabolite data supporting the BGM model of IBS, building the foundation for future mechanistic studies on the influence of gut microbial metabolites on brain function in IBS.
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349Sarnoff, R. P.; Bhatt, R. R.; Osadchiy, V.; Dong, T.; Labus, J. S.; Kilpatrick, L. A.; Chen, Z.; Subramanyam, V.; Zhang, Y.; Ellingson, B. M. A multi-omic brain gut microbiome signature differs between IBS subjects with different bowel habits. Neuropharmacology 2023, 225, 109381, DOI: 10.1016/j.neuropharm.2022.109381Google Scholar349https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtFyjtr7E&md5=a4fc547b31c0e82f5d2d7cf00b102f64A multi-omic brain gut microbiome signature differs between IBS subjects with different bowel habitsSarnoff, Rachel P.; Bhatt, Ravi R.; Osadchiy, Vadim; Dong, Tien; Labus, Jennifer S.; Kilpatrick, Lisa A.; Chen, Zixi; Subramanyam, Vishvak; Zhang, Yurui; Ellingson, Benjamin M.; Naliboff, Bruce; Chang, Lin; Mayer, Emeran A.; Gupta, ArpanaNeuropharmacology (2023), 225 (), 109381CODEN: NEPHBW; ISSN:0028-3908. (Elsevier B.V.)Alterations of the brain-gut-microbiome system (BGM) have been implicated in the pathophysiol. of irritable bowel syndrome (IBS), yet bowel habit-specific alterations have not been elucidated. In this cross-sectional study, we apply a systems biol. approach to characterize BGM patterns related to predominant bowel habit. Fecal samples and resting state fMRI were obtained from 102 premenopausal women (36 constipation-predominant IBS (IBS-C), 27 diarrhea-predominant IBS (IBS-D), 39 healthy controls (HCs)). Data integration anal. using latent components (DIABLO) was used to integrate data from the phenome, microbiome, metabolome, and resting-state connectome to predict HCs vs IBS-C vs IBS-D. Bloating and visceral sensitivity, distinguishing IBS from HC, were neg. assocd. with beneficial microbes and connectivity involving the orbitofrontal cortex. This suggests that gut interactions may generate aberrant central autonomic and descending pain pathways in IBS. The connection between IBS symptom duration, key microbes, and caudate connectivity may provide mechanistic insight to the chronicity of pain in IBS. Compared to IBS-C and HCs, IBS-D had higher levels of many key metabolites including tryptophan and phenylalanine, and increased connectivity between the sensorimotor and default mode networks; thus, suggestingan influence on diarrhea, self-related thoughts, and pain perception in IBS-D (bottom-up mechanism). IBS-Cs microbiome and metabolome resembled HCs, but IBS-C had increased connectivity in the default mode and salience networks compared to IBS-D, which may indicate importance of visceral signals, suggesting a more top-down BGM pathophysiol. These BGM characteristics highlight possible mechanistic differences for variations in the IBS bowel habit phenome.
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350Berman, S. M.; Naliboff, B. D.; Suyenobu, B.; Labus, J. S.; Stains, J.; Ohning, G.; Kilpatrick, L.; Bueller, J. A.; Ruby, K.; Jarcho, J. Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome. J. Neurosci. 2008, 28, 349– 359, DOI: 10.1523/JNEUROSCI.2500-07.2008Google Scholar350https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1c%252Fit1Gmuw%253D%253D&md5=eca766b1cc3a147861d3fd3b47599965Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndromeBerman Steven M; Naliboff Bruce D; Suyenobu Brandall; Labus Jennifer S; Stains Jean; Ohning Gordon; Kilpatrick Lisa; Bueller Joshua A; Ruby Kim; Jarcho Johanna; Mayer Emeran AThe Journal of neuroscience : the official journal of the Society for Neuroscience (2008), 28 (2), 349-59 ISSN:.Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls (p < 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS.
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351Guleria, A.; Karyampudi, A.; Singh, R.; Khetrapal, C. L.; Verma, A.; Ghoshal, U. C.; Kumar, D. Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging. J. Neurogastroenterol. Motil. 2017, 23, 415– 427, DOI: 10.5056/jnm16148Google Scholar351https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1c3mt1Cmtg%253D%253D&md5=0d7b4ad6f60058559bbf81a7effb6af3Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance ImagingGuleria Anupam; Khetrapal Chunni L; Kumar Dinesh; Karyampudi Arun; Singh Rajan; Verma Abhai; Ghoshal Uday CJournal of neurogastroenterology and motility (2017), 23 (3), 415-427 ISSN:2093-0879.BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. METHODS: Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. RESULTS: IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. CONCLUSIONS: Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain.
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352Ticinesi, A.; Milani, C.; Lauretani, F.; Nouvenne, A.; Mancabelli, L.; Lugli, G. A.; Turroni, F.; Duranti, S.; Mangifesta, M.; Viappiani, A. Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients. Sci. Rep. 2017, 7, 11102, DOI: 10.1038/s41598-017-10734-yGoogle Scholar352https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cbmvFejsQ%253D%253D&md5=33fed3dc99128e0f02be9c0e18699080Gut microbiota composition is associated with polypharmacy in elderly hospitalized patientsTicinesi Andrea; Lauretani Fulvio; Nouvenne Antonio; Maggio Marcello; Meschi Tiziana; Ticinesi Andrea; Lauretani Fulvio; Nouvenne Antonio; Maggio Marcello; Meschi Tiziana; Milani Christian; Mancabelli Leonardo; Lugli Gabriele Andrea; Turroni Francesca; Duranti Sabrina; Mangifesta Marta; Ferrario Chiara; Ventura Marco; Viappiani AliceScientific reports (2017), 7 (1), 11102 ISSN:.Reduced biodiversity and increased representation of opportunistic pathogens are typical features of gut microbiota composition in aging. Few studies have investigated their correlation with polypharmacy, multimorbidity and frailty. To assess it, we analyzed the fecal microbiota from 76 inpatients, aged 83 ± 8. Microbiome biodiversity (Chao1 index) and relative abundance of individual bacterial taxa were determined by next-generation 16S rRNA microbial profiling. Their correlation with number of drugs, and indexes of multimorbidity and frailty were verified using multivariate linear regression models. The impact of gut microbiota biodiversity on mortality, rehospitalizations and incident sepsis was also assessed after a 2-year follow-up, using Cox regression analysis. We found a significant negative correlation between the number of drugs and Chao1 Index at multivariate analysis. The number of drugs was associated with the average relative abundance of 15 taxa. The drug classes exhibiting the strongest association with single taxa abundance were proton pump inhibitors, antidepressants and antipsychotics. Conversely, frailty and multimorbidity were not significantly associated with gut microbiota biodiversity. Very low Chao1 index was also a significant predictor of mortality, but not of rehospitalizations and sepsis, at follow-up. In aging, polypharmacy may thus represent a determinant of gut microbiota composition, with detrimental clinical consequences.
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353Chopra, K.; Kumar, B.; Kuhad, A. Pathobiological targets of depression. Expert Opin. Ther. Targets 2011, 15, 379– 400, DOI: 10.1517/14728222.2011.553603Google Scholar353https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M3kvFKmtQ%253D%253D&md5=3f82d50c4e7e1d996d8e92bfadffc3fbPathobiological targets of depressionChopra Kanwaljit; Kumar Baldeep; Kuhad AnuragExpert opinion on therapeutic targets (2011), 15 (4), 379-400 ISSN:.INTRODUCTION: Depression is one of the most prevalent and life-threatening forms of mental illness associated with significant disability and mortality. About 21% of the world's population is affected by depression. AREAS COVERED: The various pathological factors involved in depression are: monoamine hypothesis, neurotransmitter receptor hypothesis, neurotrophic factor hypothesis, hypothalamic-pituitary-adrenal (HPA) dysregulation, oxidative stress, cytokine hypothesis and NO pathway. Recent drug therapies used to treat depression include: selective serotonin re-uptake inhibitors, norepinephrine and dopamine re-uptake inhibitors and several herbal drugs. The present review focuses on recently unraveled pathogenetic hypotheses and therapeutics of mental depression. Moreover, various evaluation models for antidepressants are discussed. EXPERT OPINION: Stress can be considered as a major contributor to the development of depressive disorder due to the dysregulation of HPA axis. Cytokine effects on behavior are believed to be related in part to their effects on neurotransmitter and neuropeptide function, synaptic plasticity and neuroendocrine function. Although there are multiple pathways that are involved in the pathogenesis of depression, the current antidepressants mainly target monoaminergic pathway. However, the therapeutic potential of other pathways is still under investigation. Drugs targeting NO, cytokines and the kynurenine acid pathway might be the drugs of choice in near future.
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354Dinan, T. G.; Cryan, J. F. Gut-brain axis in 2016: Brain-gut-microbiota axis - mood, metabolism and behaviour. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 69– 70, DOI: 10.1038/nrgastro.2016.200Google Scholar354https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjs1KjtA%253D%253D&md5=0089b5cedcf0749bac10b7d445a94534Gut-brain axis in 2016 Brain-gut-microbiota axis - mood, metabolism and behaviourDinan, Timothy G.; Cryan, John F.Nature Reviews Gastroenterology & Hepatology (2017), 14 (2), 69-70CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. In 2016, key studies have increased our understanding of the part played by the brain-gut-microbiota axis in disorders as diverse as depression, obesity and autism spectrum disorder. The data indicate that alterations in gut-microbial compn. can substantially affect central physiol., and that transplantation of the gut microbiota can transfer a behavioral or physiol. phenotype.
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355Foster, J. A.; McVey Neufeld, K. A. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013, 36, 305– 312, DOI: 10.1016/j.tins.2013.01.005Google Scholar355https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFSgsbw%253D&md5=fc711bb33d5e2e851f9465d2055a0e3cGut-brain axis: how the microbiome influences anxiety and depressionFoster, Jane A.; McVey Neufeld, Karen-AnneTrends in Neurosciences (2013), 36 (5), 305-312CODEN: TNSCDR; ISSN:0166-2236. (Elsevier Ltd.)A review. Within the first few days of life, humans are colonized by commensal intestinal microbiota. Here, we review recent findings showing that microbiota are important in normal healthy brain function. The authors also discuss the relation between stress and microbiota, and how alterations in microbiota influence stress-related behaviors. New studies show that bacteria, including commensal, probiotic, and pathogenic bacteria, in the gastrointestinal (GI) tract can activate neural pathways and central nervous system (CNS) signaling systems. Ongoing and future animal and clin. studies aimed at understanding the microbiota-gut-brain axis may provide novel approaches for prevention and treatment of mental illness, including anxiety and depression.
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356Halkjær, S. I.; Christensen, A. H.; Lo, B. Z. S.; Browne, P. D.; Günther, S.; Hansen, L. H.; Petersen, A. M. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut 2018, 67, 2107– 2115, DOI: 10.1136/gutjnl-2018-316434Google Scholar356https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXktVGkt7k%253D&md5=52cf8373999bc1f9b2f560e0b8fbfa34Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled studyHalkjaer, Sofie Ingdam; Christensen, Alice Hoejer; Lo, Bobby Zhao Sheng; Browne, Patrick Denis; Gunther, Stig; Hansen, Lars Hestbjerg; Petersen, Andreas MunkGut (2018), 67 (12), 2107-2115CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective IBS is assocd. with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a pos. effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clin. outcome in patients with IBS. Design We performed this study in 52 adult patients with moderate-to-severe IBS. Study visits were performed at baseline, 1, 3 and 6 mo, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected. Results A significant difference in improvement in IBS-SSS score was obsd. 3 mo after treatment (p = 0.012) favoring placebo. This was similar for IBSQoL data after 3 mo (p = 0.003) favoring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not. Conclusion In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 mo. Altering the gut microbiota is not enough to obtain clin. improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.
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357Holvoet, T.; Joossens, M.; Wang, J.; Boelens, J.; Verhasselt, B.; Laukens, D.; van Vlierberghe, H.; Hindryckx, P.; De Vos, M.; De Looze, D. Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating. Gut 2017, 66, 980– 982, DOI: 10.1136/gutjnl-2016-312513Google Scholar357https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3psFGjuw%253D%253D&md5=830da54674360cdfa132380186db373bAssessment of faecal microbial transfer in irritable bowel syndrome with severe bloatingHolvoet Tom; Laukens Debby; van Vlierberghe Hans; Hindryckx Pieter; De Vos Martine; De Looze Danny; Joossens Marie; Wang Jun; Raes Jeroen; Joossens Marie; Wang Jun; Raes Jeroen; Joossens Marie; Boelens Jerina; Verhasselt BrunoGut (2017), 66 (5), 980-982 ISSN:.There is no expanded citation for this reference.
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358Mizuno, S.; Masaoka, T.; Naganuma, M.; Kishimoto, T.; Kitazawa, M.; Kurokawa, S.; Nakashima, M.; Takeshita, K.; Suda, W.; Mimura, M. Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel Syndrome. Digestion 2017, 96, 29– 38, DOI: 10.1159/000471919Google Scholar358https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cnpslSluw%253D%253D&md5=0f7d0f0446ba20074bd9d8f2b0e99d49Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel SyndromeMizuno Shinta; Masaoka Tatsuhiro; Naganuma Makoto; Kishimoto Taishiro; Kitazawa Momoko; Kurokawa Shunya; Nakashima Moeko; Takeshita Kozue; Suda Wataru; Mimura Masaru; Hattori Masahira; Kanai TakanoriDigestion (2017), 96 (1), 29-38 ISSN:.BACKGROUND/AIMS: Dysbiosis is associated with various systemic disorders including irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) might restore intestinal microbial balance. The study aimed to determine the safety and efficacy of FMT in IBS patients, as well as also positive predictors for FMT. METHODS: This was a single-arm, open-label study. Eligible patients were diagnosed based on Rome III Diagnostic Criteria. Fecal materials were administered to the patient via colonoscopy. The primary end point was a change in the Bristol stool form scale at 4 weeks after FMT. Recovery to types 3-4 was considered a clinical response. The secondary end point was a change in intestinal microbiota and psychological status using the Hamilton Rating Scale. RESULTS: Ten patients were enrolled. Six patients achieved a clinical response. The diversity of patients 4 weeks after FMT increased significantly compared with patients before FMT, and that of responding patients was significantly higher than non-responder patients. The abundance of Bifidobacterium in effective donors was significantly higher than in ineffective donors and patients. Psychological status of all patients was significantly improved after FMT. CONCLUSIONS: FMT for patients with IBS is safe, and relatively effective. Bifidobacterium-rich fecal donor may be a positive predictor for successful FMT. Key Summary: (1) Dysbiosis is associated with various gastrointestinal disorders including IBS. (2) FMT has potential to restore intestinal microbial balance. (3) We showed that FMT improved stool form and psychological status of IBS patients. (4) Bifidobacterium-rich donor efficiently induced symbiosis in IBS patients.
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359Zoller, V.; Laguna, A. L.; Prazeres Da Costa, O.; Buch, T.; Göke, B.; Storr, M. Fecal microbiota transfer (FMT) in a patient with refractory irritable bowel syndrome. Dtsch. Med. Wochenschr. 2015, 140, 1232– 1236, DOI: 10.1055/s-0041-103798Google Scholar359https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC287itVyqsg%253D%253D&md5=5d8b7133de58d293afa3b21677da0483Fecal microbiota transfer (FMT) in a patient with refractory irritable bowel syndromeZoller Verena; Laguna Anna-Lena; Goke Burkhard; Storr Martin; Prazeres Da Costa Olivia; Buch ThorstenDeutsche medizinische Wochenschrift (1946) (2015), 140 (16), 1232-6 ISSN:.Irritable bowel syndrome is a disorder of the gastrointestinal tract with unknown etiology. Recent clinical data support a link between changes in fecal microbiota with decreased biodiversity and the development of irritable bowel syndrome. Whether these changes of the microbiota are caused by the disease or whether they develop during the course of the disease remains unclear. Several studies demonstrated that fecal microbiota transfer (FMT) successfully attenuates Clostridium difficile infection by restoring the disturbed bacterial flora of the gut and case reports suggest that FMT may relief symptoms in patients with irritable bowel syndrome (IBS). Here we report a 47-year-old male patient with longstanding refractory diarrhea predominant IBS, who was successfully treated with a single FMT. The beneficial effect on the patient's symptoms was associated with changes of the stool microbiome. Post-FMT the recipient's microbiome resembled the donor's microbiome.
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360Drago, L.; Meroni, G.; Pistone, D.; Pasquale, L.; Milazzo, G.; Monica, F.; Aragona, S.; Ficano, L.; Vassallo, R. Evaluation of main functional dyspepsia symptoms after probiotic administration in patients receiving conventional pharmacological therapies. J. Int. Med. Res. 2021, 49, 300060520982657, DOI: 10.1177/0300060520982657Google ScholarThere is no corresponding record for this reference.
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361Potter, M. D. E.; Talley, N. J. Editorial: new insights into the global prevalence of uninvestigated and functional dyspepsia. Aliment. Pharmacol. Ther. 2020, 52 (8), 1407– 1408, DOI: 10.1111/apt.16059Google Scholar361https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3s7mtlyrsg%253D%253D&md5=abc5cb19b34b96873006f9c80015fb5cEditorial: new insights into the global prevalence of uninvestigated and functional dyspepsiaPotter Michael D E; Talley Nicholas J; Potter Michael D E; Talley Nicholas J; Potter Michael D E; Talley Nicholas JAlimentary pharmacology & therapeutics (2020), 52 (8), 1407-1408 ISSN:.There is no expanded citation for this reference.
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362Zhong, L.; Shanahan, E. R.; Raj, A.; Koloski, N. A.; Fletcher, L.; Morrison, M.; Walker, M. M.; Talley, N. J.; Holtmann, G. Dyspepsia and the microbiome: time to focus on the small intestine. Gut 2017, 66, 1168– 1169, DOI: 10.1136/gutjnl-2016-312574Google Scholar362https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFGrt7fN&md5=b5b172b677fe7570bad763a4dd648e3fDyspepsia and the microbiome: time to focus on the small intestineZhong, Laurie; Shanahan, Erin R.; Raj, Ashok; Koloski, Natasha A.; Fletcher, Linda; Morrison, Mark; Walker, Marjorie M.; Talley, Nicholas J.; Holtmann, GeraldGut (2017), 66 (6), 1168-1170CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)A review. This article describes about relative abundance of bacterial genera in small intestine differences between patients with functional dyspepsia and controls.
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363Vanheel, H.; Vicario, M.; Vanuytsel, T.; Van Oudenhove, L.; Martinez, C.; Keita, Å. V.; Pardon, N.; Santos, J.; Söderholm, J. D.; Tack, J. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014, 63, 262– 271, DOI: 10.1136/gutjnl-2012-303857Google Scholar363https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXkslartro%253D&md5=94d117d7065c2e08ef8ff9eeb42f879dImpaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsiaVanheel, Hanne; Vicario, Maria; Vanuytsel, Tim; Van Oudenhove, Lukas; Martinez, Cristina; Keita, Aasa V.; Pardon, Nicolas; Santos, Javier; Soederholm, Johan D.; Tack, Jan; Farre, RicardGut (2014), 63 (2), 262-271CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiol. of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial elec. resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Nos. of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochem. Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addn., abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterized by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant assocn. between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiol. mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.
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364Liu, X. J.; Xie, W. R.; Wu, L. H.; Ye, Z. N.; Zhang, X. Y.; Zhang, R.; He, X. X. Changes in oral flora of patients with functional dyspepsia. Sci. Rep. 2021, 11, 8089, DOI: 10.1038/s41598-021-87600-5Google Scholar364https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXptFOrsL0%253D&md5=abd93f1ee6539e51861d0b45caa0663bChanges in oral flora of patients with functional dyspepsiaLiu, Xu-juan; Xie, Wen-rui; Wu, Li-hao; Ye, Zhi-ning; Zhang, Xue-yuan; Zhang, Ran; He, Xing-xiangScientific Reports (2021), 11 (1), 8089CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)To explore the changes in oral flora in people with functional dyspepsia (FD). Unstimulated saliva was collected from 21 FD patients diagnosed according to the Rome IV criteria and from 12 healthy controls (HCs) for 16SrRNA sequencing. The pH of saliva samples and community periodontal index (CPI) were tested. The prevalence of small intestinal bacterial overgrowth (SIBO) was obtained by the methane-and hydrogen-based breath test. At the phylum level, FD patients had a higher relative abundance of Spirochaetes and a lower relative abundance of Fusobacteria, TM7 and Proteobacteria than HCs (p < 0.01). In the saliva, Kingella and Abiotrophia genus levels showed significant changes between the FD and HC groups (p < 0.01). Salivary species level marker Intermedia was significantly different between FD and HC groups (p < 0.01). The oral pH of FD patients was higher than that of HCs (p < 0.01). The mean CPI of the FD group was 1.52 and that of the HC group was 0.17 (p < 0.01). Moreover, 71.4% of the FD group was pos. for SIBO. The oral flora of FD patients was different from that of HCs. Spirochaetes, Kingella, Abiotrophia, and Intermedia may be diagnostic indicators of FD.
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365Aro, P.; Talley, N. J.; Johansson, S. E.; Agréus, L.; Ronkainen, J. Anxiety Is Linked to New-Onset Dyspepsia in the Swedish Population: A 10-Year Follow-up Study. Gastroenterology 2015, 148, 928– 937, DOI: 10.1053/j.gastro.2015.01.039Google Scholar365https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MrhvV2htw%253D%253D&md5=cf3f0c9b39d4819f0a68c1beff953d4eAnxiety Is Linked to New-Onset Dyspepsia in the Swedish Population: A 10-Year Follow-up StudyAro Pertti; Talley Nicholas J; Johansson Sven-Erik; Agreus Lars; Ronkainen JukkaGastroenterology (2015), 148 (5), 928-37 ISSN:.BACKGROUND & AIMS: Functional dyspepsia (FD) is associated with anxiety but it is not clear if one causes the other. We investigated whether anxiety and depression precede the onset of FD (based on the modified Rome III criteria) and gastroesophageal reflux symptoms (GERS) in a population-based follow-up study. METHODS: Participants from the Kalixanda study (n = 3000), randomly selected from the national population register of Sweden, were given the validated Abdominal Symptom Questionnaire 1998-2001; 1000 of these participants then were selected randomly to undergo esophagogastroduodenoscopy and were given the Abdominal Symptom Questionnaire along with the Hospital Anxiety and Depression Scale questionnaire. All eligible subjects who underwent endoscopy (n = 887) were invited to participate in a follow-up study in June-August 2010 and were given the same questionnaires. Data were analyzed by logistic regression. RESULTS: Of the 703 subjects who completed the follow-up questionnaires (79.3%); 110 were found to have FD at baseline (15.6%) and 93 at the follow-up examination (13.3%); 48 of these were new cases of FD. GERS without organic disease was reported by 273 individuals (38.8%) at baseline and by 280 at follow-up examination (39.8%); 93 cases were new. Major anxiety was associated with FD at the follow-up evaluation (odds ratio [OR], 6.30; 99% confidence interval [CI], 1.64-24.16). Anxiety was associated with postprandial distress syndrome at baseline (OR, 4.83; 99% CI, 1.24-18.76) and at the follow-up examination (OR, 8.12; 99% CI, 2.13-30.85), but not with epigastric pain syndrome. Anxiety at baseline was associated with new-onset FD at the follow-up examination (OR, 7.61; 99% CI, 1.21-47.73), but not with GERS. CONCLUSIONS: In a study of the Swedish population, anxiety at baseline, but not depression, increased the risk for development of FD by 7.6-fold in the next 10 years. Anxiety did not affect risk for GERS.
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366Van Oudenhove, L.; Aziz, Q. The role of psychosocial factors and psychiatric disorders in functional dyspepsia. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 158– 167, DOI: 10.1038/nrgastro.2013.10Google Scholar366https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3szjt12gsg%253D%253D&md5=93003eb3730cc03c84bfb391e3a24861The role of psychosocial factors and psychiatric disorders in functional dyspepsiaVan Oudenhove Lukas; Aziz QasimNature reviews. Gastroenterology & hepatology (2013), 10 (3), 158-67 ISSN:.In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.
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367Hannibal, K. E.; Bishop, M. D. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys. Ther. 2014, 94, 1816– 1825, DOI: 10.2522/ptj.20130597Google Scholar367https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cbjtlGisg%253D%253D&md5=7ea82a617a15f017a88bc9d54a27b67eChronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitationHannibal Kara E; Bishop Mark DPhysical therapy (2014), 94 (12), 1816-25 ISSN:.Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to facilitate treatment, prevent chronic disability, and improve quality of life.
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368Koloski, N. A.; Jones, M.; Kalantar, J.; Weltman, M.; Zaguirre, J.; Talley, N. J. The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut 2012, 61, 1284– 1290, DOI: 10.1136/gutjnl-2011-300474Google Scholar368https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38vgtFOnsA%253D%253D&md5=983db78675e60e2b09acbcf781152011The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based studyKoloski N A; Jones M; Kalantar J; Weltman M; Zaguirre J; Talley N JGut (2012), 61 (9), 1284-90 ISSN:.OBJECTIVE: Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain-gut mechanism in FGIDs. DESIGN: Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. RESULTS: Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up. CONCLUSIONS: The central nervous system and gut interact bidirectionally in FGIDs.
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369Cryan, J. F.; Dinan, T. G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 2012, 13, 701– 712, DOI: 10.1038/nrn3346Google Scholar369https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlamurvN&md5=d88f108ce34ee7792c15f3d7afb1b054Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviourCryan, John F.; Dinan, Timothy G.Nature Reviews Neuroscience (2012), 13 (10), 701-712CODEN: NRNAAN; ISSN:1471-003X. (Nature Publishing Group)A review. Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biol. Studies are revealing how variations and changes in the compn. of the gut microbiota influence normal physiol. and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS - possibly through neural, endocrine and immune pathways - and thereby influences brain function and behavior. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
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370Browning, K. N.; Travagli, R. A. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol 2014, 4, 1339– 1368, DOI: 10.1002/cphy.c130055Google Scholar370https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MzhtFyqug%253D%253D&md5=cc4c30fb531fd094275f297a9df79bd4Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functionsBrowning Kirsteen N; Travagli R AlbertoComprehensive Physiology (2014), 4 (4), 1339-68 ISSN:.Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathetic nervous system exerts a predominantly inhibitory effect upon GI muscle and provides a tonic inhibitory influence over mucosal secretion while, at the same time, regulates GI blood flow via neurally mediated vasoconstriction. The parasympathetic nervous system, in contrast, exerts both excitatory and inhibitory control over gastric and intestinal tone and motility. Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the higher CNS centers influence homeostatic control as well as cognitive and behavioral functions. This review will describe the basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways. The role of CNS-centered reflexes in the regulation of GI functions will be discussed as will modulation of these reflexes under both physiological and pathophysiological conditions. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide these answers.
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371Barberio, B.; Judge, C.; Savarino, E. V.; Ford, A. C. Global prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2021, 6, 638– 648, DOI: 10.1016/S2468-1253(21)00111-4Google Scholar371https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c7ksFWktg%253D%253D&md5=1364c3612427e99e5ee47aabeb4df7baGlobal prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysisBarberio Brigida; Savarino Edoardo V; Judge Ciaran; Ford Alexander CThe lancet. Gastroenterology & hepatology (2021), 6 (8), 638-648 ISSN:.BACKGROUND: Functional constipation is a common functional bowel disorder in the community, which has a varying prevalence across cross-sectional surveys. We did a contemporaneous systematic review and meta-analysis of studies using comparable methodology and all iterations of the Rome criteria to estimate the global prevalence of functional constipation. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Embase Classic from Jan 1, 1990, to Dec 31, 2020, to identify population-based cross-sectional studies comprising at least 50 participants that reported the prevalence of functional constipation in adults (age 18 years and older) according to Rome I, II, III, or IV criteria. We excluded studies that reported the prevalence of functional constipation in convenience samples. We extracted prevalence estimates of functional constipation from eligible studies, according to the study criteria used to define it. For each study, we extracted data for country; method of data collection; criteria used to define functional constipation; whether the study used the Rome I, II, III, or IV diagnostic questionnaires or approximated these definitions of the condition using another questionnaire; the total number of participants providing complete data; age; the number of participants with the condition; the number of male and female participants; and the number of male and female participants with the condition. We calculated pooled prevalence, odds ratios (OR), and 95% CIs. FINDINGS: Of 8174 citations evaluated, 45 studies fulfilled the eligibility criteria, representing 80 separate populations and comprising 275 260 participants. The pooled prevalence of functional constipation was 15·3% (95% CI 8·1-24·4, I(2)=99·4%) in studies using the Rome I criteria, 11·2% (7·9-14·9; I(2)=99·6%) in studies that used Rome II criteria, 10·4% (6·5-14·9; I(2)=99·8%) in those that used Rome III criteria, and 10·1% (8·7-11·6; I(2)=98·2%) when Rome IV criteria were used. Prevalence of functional constipation was higher in women, irrespective of the Rome criteria used (OR 2·40 [95% CI 2·02-2·86] for Rome I, 1·94 [1·46-2·57] for Rome II, and 2·32 [1·85-2·92] for Rome III; no studies using Rome IV criteria reported prevalence by sex). There was significant heterogeneity between studies in all of our analyses, which persisted even when the same criteria were applied and similar methodologies used. INTERPRETATION: Even when uniform symptom-based criteria are used to define the presence of functional constipation, prevalence varies between countries. Thus, environmental, cultural, ethnic, dietary, or genetic factors can influence reporting of symptoms. Future studies should aim to elucidate reasons for this geographical variability. FUNDING: None.
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372Vriesman, M. H.; Koppen, I. J. N.; Camilleri, M.; Di Lorenzo, C.; Benninga, M. A. Management of functional constipation in children and adults. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 21– 39, DOI: 10.1038/s41575-019-0222-yGoogle Scholar372https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MjlsFKntA%253D%253D&md5=2e096fc7ff8299c85771d44fb87110afManagement of functional constipation in children and adultsVriesman Mana H; Koppen Ilan J N; Benninga Marc A; Camilleri Michael; Di Lorenzo CarloNature reviews. Gastroenterology & hepatology (2020), 17 (1), 21-39 ISSN:.Functional constipation is common in children and adults worldwide. Functional constipation shows similarities in children and adults, but important differences also exist regarding epidemiology, symptomatology, pathophysiology, diagnostic workup and therapeutic management. In children, the approach focuses on the behavioural nature of the disorder and the initial therapeutic steps involve toilet training and laxatives. In adults, management focuses on excluding an underlying cause and differentiating between different subtypes of functional constipation - normal transit, slow transit or an evacuation disorder - which has important therapeutic consequences. Treatment of adult functional constipation involves lifestyle interventions, pelvic floor interventions (in the presence of a rectal evacuation disorder) and pharmacological therapy. When conventional treatments fail, children and adults are considered to have intractable functional constipation, a troublesome and distressing condition. Intractable constipation is managed with a stepwise approach and in rare cases requires surgical interventions such as antegrade continence enemas in children or colectomy procedures for adults. New drugs, including prokinetic and prosecretory agents, and surgical strategies, such as sacral nerve stimulation, have the potential to improve the management of children and adults with intractable functional constipation.
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373Zhuang, M.; Shang, W.; Ma, Q.; Strappe, P.; Zhou, Z. Abundance of Probiotics and Butyrate-Production Microbiome Manages Constipation via Short-Chain Fatty Acids Production and Hormones Secretion. Mol. Nutr. Food Res. 2019, 63, e1801187, DOI: 10.1002/mnfr.201801187Google Scholar373https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVSlsb%252FK&md5=cf656b161ae6883d058bd6143ae1a23bAbundance of Probiotics and Butyrate-Production Microbiome Manages Constipation via Short-Chain Fatty Acids Production and Hormones SecretionZhuang, Min; Shang, Wenting; Ma, Qiuchen; Strappe, Padraig; Zhou, ZhongkaiMolecular Nutrition & Food Research (2019), 63 (23), 1801187CODEN: MNFRCV; ISSN:1613-4125. (Wiley-VCH Verlag GmbH & Co. KGaA)Scope : The characteristics of gut microbiota and host metab. are hypothesized to be assocd. with constipation status, but the regulation mechanism is not fully understood. Thus, the current study investigates the effect of constipation symptoms on gut functionality following the modulation of gut microbiota and metabolites via dietary fiber intervention. Methods and results : Constipation causes a significantly reduced short-chain fatty acids (SCFAs) prodn. and a higher level of iso-butyrate. The feces of constipated people are characterized with inhibited Faecalibacterium, Ruminococcaceae and Roseburia abundance. Desulfovibrionaceae is identified to be an important endotoxin producer in constipated patients, and a butyrate-enriched SCFAs profile achieved by dietary fiber supplement accelerates gastrointestinal transit and increases the thickness of the mucosal layer, possibly through triggering the secretion of colonic hormones and enhancing the expression of tight junction proteins for maintaining intestinal barrier integrity. More importantly, an interacting regulatory mechanism among SCFAs, in particular butyrate and propionate, may be involved in signaling between the microbiome and host cells in the colon. Conclusion : Gut microbiota, characterized with enriched butyrate-producing and depressed Desulfovibrionaceae bacteria, attenuates constipation symptoms through promoting intestinal hormones secretion and maintaining gut barrier integrity.
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374Attaluri, A.; Jackson, M.; Valestin, J.; Rao, S. S. Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS. Am. J. Gastroenterol. 2010, 105, 1407– 1411, DOI: 10.1038/ajg.2009.655Google Scholar374https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3czpsVKjsA%253D%253D&md5=c85e203042559f239b4bc67b33010d76Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBSAttaluri Ashok; Jackson Michelle; Valestin Jessica; Rao Satish S CThe American journal of gastroenterology (2010), 105 (6), 1407-11 ISSN:.OBJECTIVES: About 35% of humans have methane-producing gut flora. Methane-producing irritable bowel syndrome (IBS) subjects are generally constipated. In animal models, methane infusion slows intestinal transit. Whether methanogenic flora alters colonic transit or stool characteristics and its relationship to constipation is unclear. The aim of this study was to examine the prevalence and association of methanogenic flora in patients with slow transit (ST) constipation and normal transit (NT) constipation and non-constipated controls. METHODS: Ninety-six consecutive subjects with chronic constipation (CC) (Rome III) were evaluated with radio-opaque marker (ROM) transit studies and were classified as ST (>20% ROM retention) or NT. All constipated subjects and 106 non-constipated controls underwent breath tests to assess methane production. Baseline CH4 of >or=3 p.p.m. was used to define presence of methanogenic flora. Stool frequency and consistency were assessed using a prospective stool diary. Correlation analyses were performed. RESULTS: Forty-eight subjects had ST and 48 had NT. Prevalence of methanogenic flora was higher (P<0.05) in ST (75%) compared to NT (44%) or controls (28%). ST patients had higher methane production compared to NT and controls (P<0.05). NT patients also produced more methane compared to controls (P<0.05). There was moderate(P<0.05) correlation among baseline, peak, and area under the curve (AUC) of methane response with colonic transit but not with stool characteristics. CONCLUSIONS: Presence of methanogenic flora is associated with CC. Methane production after carbohydrate challenge and its prevalence were higher in ST than NT, although stool characteristics were similar in both groups. Methane production correlated with colonic transit, suggesting an association with stool transport but not with stool characteristics.
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375Chen, Y.; Wu, T.; Lu, W.; Yuan, W.; Pan, M.; Lee, Y. K.; Zhao, J.; Zhang, H.; Chen, W.; Zhu, J. Predicting the Role of the Human Gut Microbiome in Constipation Using Machine-Learning Methods: A Meta-Analysis. Microorganisms 2021, 9, 2149, DOI: 10.3390/microorganisms9102149Google Scholar375https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXivVWlu7nE&md5=8adcc0f5cee52d46f6a2f211545ddc13Predicting the Role of the Human Gut Microbiome in Constipation Using Machine-Learning Methods: A Meta-AnalysisChen, Yutao; Wu, Tong; Lu, Wenwei; Yuan, Weiwei; Pan, Mingluo; Lee, Yuan-Kun; Zhao, Jianxin; Zhang, Hao; Chen, Wei; Zhu, Jinlin; Wang, HongchaoMicroorganisms (2021), 9 (10), 2149CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Constipation is a common condition that affects the health and the quality of life of patients. Recent studies have suggested that the gut microbiome is assocd. with constipation, but these studies were mainly focused on a single research cohort. Thus, we aimed to construct a classification model based on fecal bacterial and identify the potential gut microbes' biomarkers. We collected 3056 fecal amplicon sequence data from five research cohorts. The data were subjected to a series of analyzes, including alpha- and beta-diversity analyzes, phylogenetic profiling analyzes, and systematic machine learning to obtain a comprehensive understanding of the assocn. between constipation and the gut microbiome. The alpha diversity of the bacterial community compn. was higher in patients with constipation. Beta diversity anal. evidenced significant partitions between the two groups on the base of gut microbiota compn. Further, machine learning based on feature selection was performed to evaluate the utility of the gut microbiome as the potential biomarker for constipation. The Gradient Boosted Regression Trees after chi2 feature selection was the best model, exhibiting a validation performance of 70.7% . We constructed an accurate constipation discriminant model and identified 15 key genera, including Serratia, Dorea, and Aeromonas, as possible biomarkers for constipation.
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376Tian, H.; Ye, C.; Yang, B.; Cui, J.; Zheng, Z.; Wu, C.; Zhou, S.; Lv, X.; Qin, N.; Qin, H. Gut Metagenome as a Potential Diagnostic and Predictive Biomarker in Slow Transit Constipation. Front. Med. 2022, 8, 777961, DOI: 10.3389/fmed.2021.777961Google ScholarThere is no corresponding record for this reference.
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377Sartor, R. B. Optimal sampling of the intestinal microbiota for research. Nature Reviews Gastroenterology & Hepatology 2015, 12, 253– 254, DOI: 10.1038/nrgastro.2015.46Google Scholar377https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MnntFWrsg%253D%253D&md5=46baa3f95fc32b226f0e214977f52e8dGut microbiota: Optimal sampling of the intestinal microbiota for researchSartor R BalfourNature reviews. Gastroenterology & hepatology (2015), 12 (5), 253-4 ISSN:.There is no expanded citation for this reference.
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378Swidsinski, A.; Loening-Baucke, V.; Verstraelen, H.; Osowska, S.; Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 2008, 135, 568– 579, DOI: 10.1053/j.gastro.2008.04.017Google Scholar378https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1crgslWhsQ%253D%253D&md5=cbafe518ff3d830ea9bdd165cdaecaebBiostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrheaSwidsinski Alexander; Loening-Baucke Vera; Verstraelen Hans; Osowska Sylwia; Doerffel YvonneGastroenterology (2008), 135 (2), 568-79 ISSN:.BACKGROUND & AIMS: Dysbiosis is a key component of intestinal disorders. Our aim was to quantitatively access the biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea and evaluate the responses to Saccharomyces boulardii treatment. METHODS: We investigated punched fecal cylinders from 20 patients with chronic idiopathic diarrhea and 20 healthy controls using fluorescence in situ hybridization. Fluctuations in assembly of 11 bacterial groups were monitored weekly for 3 weeks before, during, and after oral S boulardii supplementation. RESULTS: The structural organization of fecal microbiota in healthy subjects was stable and unaffected by S boulardii. The assembly of fecal microbiota in idiopathic diarrhea was markedly different, characterized by mucus depositions within feces; mucus septa and striae; marked reduction in concentrations of habitual Eubacterium rectale, Bacteroides, and Faecalibacterium prausnitzii groups; suppression of bacterial fluorescence in the center of the feces; increased concentrations and spatial shift of mucotrop bacteria to the fecal core; and increased concentrations of occasional bacteria. Except for elevated concentrations of some occasional bacterial groups, all parameters typical for diarrhea improved significantly with S boulardii treatment and most changes persisted after cessation of therapy. The improvement of the fecal microbiota was accompanied by partial (40%) and complete normalization (30%) of the diarrheal symptoms. CONCLUSIONS: The fecal microbiota is highly structured. Fluorescence in situ hybridization analysis allowed us to quantitatively study the dysbiotic changes. S boulardii significantly improved the fecal biostructure in patients with diarrhea but had no influence on the feces in healthy subjects.
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379Durbán, A.; Abellán, J. J.; Jiménez-Hernández, N.; Salgado, P.; Ponce, M.; Ponce, J.; Garrigues, V.; Latorre, A.; Moya, A. Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome. Environ. Microbiol. Rep. 2012, 4, 242– 247, DOI: 10.1111/j.1758-2229.2012.00327.xGoogle Scholar379https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmsVKit7Y%253D&md5=72b2d693eeec0219ab30c2fde6edb68fStructural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndromeDurban, Ana; Abellan, Juan J.; Jimenez-Hernandez, Nuria; Salgado, Patricia; Ponce, Marta; Ponce, Julio; Garrigues, Vicente; Latorre, Amparo; Moya, AndresEnvironmental Microbiology Reports (2012), 4 (2), 242-247CODEN: EMRNAG; ISSN:1758-2229. (Wiley-Blackwell)Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in western countries. Previous studies on IBS, mostly based on fecal samples, suggest alterations in the intestinal microbiota. However, no consensus has been reached regarding the assocn. between specific bacteria and IBS. We explore the alterations of intestinal bacterial communities in IBS using massive sequencing of amplified 16S rRNA genes. Mucosal biopsies of the ascending and descending colon and feces from 16 IBS patients and 9 healthy controls were analyzed. Strong inter-individual variation was obsd. in the compn. of the bacterial communities in both patients and controls. These communities showed less diversity in IBS cases. There were larger differences in the microbiota compn. between biopsies and feces than between patients and controls. We found a few over-represented and under-represented taxa in IBS cases with respect to controls. The detected alterations varied by site, with no changes being consistent across sample types.
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380Parthasarathy, G.; Chen, J.; Chen, X.; Chia, N.; O’Connor, H. M.; Wolf, P. G.; Gaskins, H. R.; Bharucha, A. E. Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation. Gastroenterology 2016, 150, 367– 379.e1, DOI: 10.1053/j.gastro.2015.10.005Google Scholar380https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28zhsFChuw%253D%253D&md5=cf6cebd32bf979c44e3632c67faf0a16Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic ConstipationParthasarathy Gopanandan; Chen Jun; Chia Nicholas; Chen Xianfeng; O'Connor Helen M; Wolf Patricia G; Gaskins H Rex; Bharucha Adil EGastroenterology (2016), 150 (2), 367-79.e1 ISSN:.BACKGROUND & AIMS: In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. METHODS: Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). RESULTS: Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. CONCLUSIONS: After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation.
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381Procházková, N.; Falony, G.; Dragsted, L. O.; Licht, T. R.; Raes, J.; Roager, H. M. Advancing human gut microbiota research by considering gut transit time. Gut 2023, 72, 180– 191, DOI: 10.1136/gutjnl-2022-328166Google Scholar381https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtFKms7vO&md5=db48f64ad3b3aa7bf209854a1bdc6aebAdvancing human gut microbiota research by considering gut transit timeProchazkova, Nicola; Falony, Gwen; Dragsted, Lars Ove; Licht, Tine Rask; Raes, Jeroen; Roager, Henrik M.Gut (2023), 72 (1), 180-191CODEN: GUTTAK; ISSN:0017-5749. (BMJ)A review. Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota compn. and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota compn. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota compn., diversity and metab. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet-microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.
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382Hosseinzadeh, S. T.; Poorsaadati, S.; Radkani, B.; Forootan, M. Psychological disorders in patients with chronic constipation. Gastroenterol. Hepatol. Bed Bench 2011, 4, 159– 163Google Scholar382https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cjjsVKntg%253D%253D&md5=a3496c2366660a693ad92ef59d6d206cPsychological disorders in patients with chronic constipationHosseinzadeh Sahar Tahbaz; Poorsaadati Sara; Radkani Babak; Forootan MojganGastroenterology and hepatology from bed to bench (2011), 4 (3), 159-63 ISSN:2008-2258.AIM: The aim of present study was to screen two categories of psychiatric disorders in chronic functional constipation. BACKGROUND: It has been established that the prevalence of mood and anxiety disorders among patients with functional gastrointestinal disorders is higher than in the general population. PATIENTS AND METHODS: Fifty four constipated patients were recruited from patients referred to the motility disorder department of Research Center for Gastroentrology and Liver Diseases, and screened for psychiatric disorders using HADS (Hospital Anxiety and Depression Scale) and MINI (Mini International Neuropsychiatric Interview). RESULTS: The results showed a relatively high prevalence of anxiety and depression both in HADS (33.3% and 22.2% respectively) and MINI (33.3% and 31.5% respectively). CONCLUSION: Based on our results the prevalence of mood and anxiety disorders in constipated patients is much higher than general population and in order to reduce health care costs for constipated patients, we need to have an intervention program for comorbid psychological dysfunctions which affect the course of gastrointestinal disorders.
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383Duan, S.; Liu, L.; Li, G.; Wang, J.; Hu, Y.; Zhang, W.; Tan, Z.; Jia, Z.; Zhang, L.; von Deneen, K. M. Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation. Front. Neurosci. 2021, 15, 628880, DOI: 10.3389/fnins.2021.628880Google Scholar383https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sfjt1Wrsg%253D%253D&md5=5031575d2818003f70e06bc5c1d2b1f8Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional ConstipationDuan Shijun; Cui Guangbin; Liu Lei; Li Guanya; Wang Jia; Hu Yang; Zhang Wenchao; Tan Zongxin; Jia Zhenzhen; Zhang Lei; von Deneen Karen M; Zhang Yi; Nie YongzhanFrontiers in neuroscience (2021), 15 (), 628880 ISSN:1662-4548.Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)-rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex-rACC, PreCen-aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN-SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.
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384Hu, C.; Liu, L.; Liu, L.; Zhang, J.; Hu, Y.; Zhang, W.; Ding, Y.; Wang, Y.; Zhang, Z.; von Deneen, K. M. Cortical morphometry alterations in brain regions involved in emotional, motor-control and self-referential processing in patients with functional constipation. Brain Imaging Behav. 2020, 14, 1899– 1907, DOI: 10.1007/s11682-019-00133-4Google Scholar384https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M3os1Oksw%253D%253D&md5=d8f15908d489fde802726cfec4cde8aeCortical morphometry alterations in brain regions involved in emotional, motor-control and self-referential processing in patients with functional constipationHu Chunxin; Liu Li; Liu Lei; Hu Yang; Zhang Wenchao; Ding Yueyan; Wang Yuanyuan; Zhang Zhida; von Deneen Karen M; Zhang Yi; Zhang Junwang; Nie Yongzhan; Qian Long; Wang Huaning; Duan Shijun; Cui Guangbin; Wang FanBrain imaging and behavior (2020), 14 (5), 1899-1907 ISSN:.Functional constipation (FC) is a common functional gastrointestinal disorder (FGID). Neuroimaging studies on patients with FC showed brain functional abnormalities in regions involved in emotional process modulation, somatic and sensory processing and motor control. Brain structural imaging studies in patients with FGID have also shown disease-related alterations in cortical morphometry, but whether and how FC affects brain structure remains unclear. Structural Magnetic Resonance Imaging and surface-based morphometry analysis were used to investigate the impact of FC on cortical morphometry in 29 patients with FC and 29 healthy controls (HC). Results showed that patients with FC compared to HC had significantly decreased cortical thickness in the left middle frontal gyrus (MFG), dorsomedial (DMPFC) and ventromedial prefrontal gyrus (VMPFC), right dorsal anterior cingulate cortex (dACC), left orbitofrontal cortex (OFC), posterior cingulate cortex (PCC)/precuneus, middle temporal gyrus (MTG), and supplementary motor area (SMA) (P < 0.01). Correlation analysis showed that sensation of incomplete evacuation was negatively correlated with cortical thickness in the SMA (P < 0.0001). In addition, patients with FC also had decreased cortical volume than HC in the MTG, precentral gyrus (PreCen) and precuneus/cuneus (P < 0.01), as well as decreased cortical surface area in the PreCen (P < 0.01). No correlation was found between cortical volume/surface area and behavioral measures. These findings suggest that patients with FC are associated with cortical morphometric abnormalities in brain regions implicated in somatic/motor-control, emotional processing and self-referential processing.
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385Jin, Q.; Duan, S.; Li, G.; Sun, L.; Hu, Y.; Hu, C.; Zhao, J.; von Deneen, K. M.; Qian, L.; Wang, H. Sex-related differences in resting-state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation. Neurogastroenterol. Motil. 2019, 31, e13566, DOI: 10.1111/nmo.13566Google ScholarThere is no corresponding record for this reference.
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386Li, G.; Zhang, W.; Hu, Y.; Wang, J.; Li, J.; Jia, Z.; Zhang, L.; Sun, L.; von Deneen, K. M.; Duan, S. Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders. Psychosom. Med. 2021, 83, 707– 714, DOI: 10.1097/PSY.0000000000000958Google Scholar386https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c7ntFKquw%253D%253D&md5=9f73f08c89e19547885135febd13147fDistinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive DisordersLi Guanya; Zhang Wenchao; Hu Yang; Wang Jia; Li Jingyuan; Jia Zhenzhen; Zhang Lei; Sun Lijuan; von Deneen Karen M; Duan Shijun; Wang Huaning; Wu Kaichun; Fan Daiming; Cui Guangbin; Zhang Yi; Nie YongzhanPsychosomatic medicine (2021), 83 (7), 707-714 ISSN:.OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.
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387Liu, L.; Hu, C.; Hu, Y.; Zhang, W.; Zhang, Z.; Ding, Y.; Wang, Y.; von Deneen, K. M.; Sun, L.; Wang, H. Abnormalities in the thalamo-cortical network in patients with functional constipation. Brain Imaging Behav. 2021, 15, 630– 642, DOI: 10.1007/s11682-020-00273-yGoogle Scholar387https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38znsFyjsA%253D%253D&md5=87efccc9c08eb909fc5c6fff9a196d48Abnormalities in the thalamo-cortical network in patients with functional constipationLiu Lei; Hu Chunxin; Hu Yang; Zhang Wenchao; Zhang Zhida; Ding Yueyan; Wang Yuanyuan; von Deneen Karen M; Liu Jixin; Zhang Yi; Sun Lijuan; Nie Yongzhan; Wang Huaning; Duan Shijun; Cui Guangbin; Mao Kuanrong; Wang FanBrain imaging and behavior (2021), 15 (2), 630-642 ISSN:.Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.
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388Peihong, M.; Tao, Y.; Zhaoxuan, H.; Sha, Y.; Li, C.; Kunnan, X.; Jingwen, C.; Likai, H.; Yuke, T.; Yuyi, G. Alterations of White Matter Network Properties in Patients With Functional Constipation. Front. Neurol. 2021, 12, 627130, DOI: 10.3389/fneur.2021.627130Google Scholar388https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sfps1Oiug%253D%253D&md5=ddda1505946ed80f6542de1d87f20c55Alterations of White Matter Network Properties in Patients With Functional ConstipationPeihong Ma; Tao Yin; Zhaoxuan He; Sha Yang; Li Chen; Kunnan Xie; Jingwen Chen; Likai Hou; Yuke Teng; Yuyi Guo; Fumin Wang; Zilei Tian; Ruirui Sun; Fang Zeng; Peihong Ma; Tao Yin; Zhaoxuan He; Sha Yang; Li Chen; Kunnan Xie; Jingwen Chen; Likai Hou; Yuke Teng; Yuyi Guo; Fumin Wang; Zilei Tian; Ruirui Sun; Fang ZengFrontiers in neurology (2021), 12 (), 627130 ISSN:1664-2295.Background: The abnormalities in brain function and structure of patients with functional constipation (FC) have been identified using multiple neuroimaging studies and have confirmed the abnormal processing of visceral sensation at the level of the central nervous system (CNS) as an important reason for FC. As an important basis for central information transfer, the role of the white matter (WM) networks in the pathophysiology of FC has not been investigated. This study aimed to explore the topological organization of WM networks in patients with FC and its correlation with clinical variables. Methods and Analysis: In this study, 70 patients with FC and 45 age- and gender-matched healthy subjects (HS) were recruited. Diffusion tensor imaging (DTI) data and clinical variables were acquired from each participant. WM networks were constructed using the deterministic fiber tracking approach, and the global and nodal properties of the WM networks were compared using graph theory analysis between patients with FC and HS. The relationship between the representative nodal characteristics-nodal betweenness and clinical parameters was assessed using partial correlation analysis. Results: Patients with FC showed increased nodal characteristics in the left superior frontal gyrus (orbital part), right middle frontal gyrus (orbital part), and right anterior cingulate and paracingulate (P < 0.05, corrected for false discovery rate) and decreased nodal characteristics in the left caudate and left thalamus (P < 0.05, corrected for false discovery rate) compared with HS. The duration of FC was negatively correlated with the nodal betweenness of the left thalamus (r = -0.354, P = 0.04, corrected for false discovery rate). Conclusion: The results indicated the alternations in WM networks of patients with FC and suggested the abnormal visceral sensation processing in the CNS from the perspective of large-scale brain WM network.
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389Zhu, Q.; Cai, W.; Zheng, J.; Li, G.; Meng, Q.; Liu, Q.; Zhao, J.; von Deneen, K. M.; Wang, Y.; Cui, G. Distinct resting-state brain activity in patients with functional constipation. Neurosci. Lett. 2016, 632, 141– 146, DOI: 10.1016/j.neulet.2016.08.042Google Scholar389https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsV2rtrrO&md5=c5385b3f0966e0a80f804c6efc92e11dDistinct resting-state brain activity in patients with functional constipationZhu, Qiang; Cai, Weiwei; Zheng, Jianyong; Li, Guanya; Meng, Qianqian; Liu, Qiaoyun; Zhao, Jizheng; von Deneen, Karen M.; Wang, Yuanyuan; Cui, Guangbin; Duan, Shijun; Han, Yu; Wang, Huaning; Tian, Jie; Zhang, Yi; Nie, YongzhanNeuroscience Letters (2016), 632 (), 141-146CODEN: NELED5; ISSN:0304-3940. (Elsevier Ireland Ltd.)Functional constipation (FC) is a common functional gastrointestinal disorder (FGID) with a higher prevalence in clin. practice. The primary brain regions involved in emotional arousal regulation, somatic, sensory and motor control processing have been identified with neuroimaging in FGID. It remains unclear how these factors interact to influence the baseline brain activity of patients with FC. In the current study, we combined resting-state fMRI (RS-fMRI) with Granger causality anal. (GCA) to investigate the causal interactions of the brain areas in 14 patients with FC and in 26 healthy controls (HC). Our data showed significant differences in baseline brain activities in a no. of major brain regions implicated in emotional process modulation (i.e. dorsal anterior cingulate cortex-dACC, anterior insula-aINS, orbitofrontal cortex-OFC, hippocampus-HIPP), somatic and sensory processing, and motor control (i.e., supplementary motor area-SMA, precentral gyrus-PreCen) (P < 0.05, FDR correction). The GCA results revealed stronger effective connectivity from the OFC and dACC, which are regions involved with emotional regulation, propel limbic regions at the aINS and HIPP to induce abnormal emotional processing regulating visceral responses; and weaker effective connectivity from the SMA and PreCen, which are regions involved with somatic, sensory and motor control, propel the aINS and HIPP, suggesting abnormalities of sensory and behavioral responses. Such information of basal level functional abnormalities expands our current understanding of neural mechanisms underlying functional constipation.
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390Mayer, E. A. Gut feelings: the emerging biology of gut–brain communication. Nat. Rev. Neurosci. 2011, 12, 453– 466, DOI: 10.1038/nrn3071Google Scholar390https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXoslynsLY%253D&md5=7d6d83bdc389070ef5902435a335ead0Gut feelings: the emerging biology of gut-brain communicationMayer, Emeran A.Nature Reviews Neuroscience (2011), 12 (8), 453-466CODEN: NRNAAN; ISSN:1471-003X. (Nature Publishing Group)A review. The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language. Recent neurobiol. insights into this gut-brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making. Moreover, disturbances of this system have been implicated in a wide range of disorders, including functional and inflammatory gastrointestinal disorders, obesity and eating disorders.
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391Rubio, A.; Van Oudenhove, L.; Pellissier, S.; Ly, H. G.; Dupont, P.; Lafaye de Micheaux, H.; Tack, J.; Dantzer, C.; Delon-Martin, C.; Bonaz, B. Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers. NeuroImage 2015, 107, 10– 22, DOI: 10.1016/j.neuroimage.2014.11.043Google Scholar391https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MzlsFehtw%253D%253D&md5=23c620d64a51b6bcdb828c2f8bda6ef4Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteersRubio Amandine; Van Oudenhove Lukas; Pellissier Sonia; Ly Huynh Giao; Tack Jan; Dupont Patrick; Lafaye de Micheaux Hugo; Delon-Martin Chantal; Dantzer Cecile; Bonaz BrunoNeuroImage (2015), 107 (), 10-22 ISSN:.The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases.
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392Molina-Torres, G.; Rodriguez-Arrastia, M.; Roman, P.; Sanchez-Labraca, N.; Cardona, D. Stress and the gut microbiota-brain axis. Behav. Pharmacol. 2019, 30, 187– 200, DOI: 10.1097/FBP.0000000000000478Google Scholar392https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cbhsFaitg%253D%253D&md5=8be6a31e1f4533b89310b431ad7c6af7Stress and the gut microbiota-brain axisMolina-Torres Guadalupe; Rodriguez-Arrastia Miguel; Roman Pablo; Sanchez-Labraca Nuria; Cardona DianaBehavioural pharmacology (2019), 30 (2 and 3-Spec Issue), 187-200 ISSN:.Stress is a nonspecific response of the body to any demand imposed upon it, disrupting the body homoeostasis and manifested with symptoms such as anxiety, depression or even headache. These responses are quite frequent in the present competitive world. The aim of this review is to explore the effect of stress on gut microbiota. First, we summarize evidence of where the microbiota composition has changed as a response to a stressful situation, and thereby the effect of the stress response. Likewise, we review different interventions that can modulate microbiota and could modulate the stress according to the underlying mechanisms whereby the gut-brain axis influences stress. Finally, we review both preclinical and clinical studies that provide evidence of the effect of gut modulation on stress. In conclusion, the influence of stress on gut microbiota and gut microbiota on stress modulation is clear for different stressors, but although the preclinical evidence is so extensive, the clinical evidence is more limited. A better understanding of the mechanism underlying stress modulation through the microbiota may open new avenues for the design of therapeutics that could boost the pursued clinical benefits. These new designs should not only focus on stress but also on stress-related disorders such as anxiety and depression, in both healthy individuals and different populations.
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393Vanuytsel, T.; van Wanrooy, S.; Vanheel, H.; Vanormelingen, C.; Verschueren, S.; Houben, E.; Salim Rasoel, S.; Tóth, J.; Holvoet, L.; Farré, R. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 2014, 63, 1293– 1299, DOI: 10.1136/gutjnl-2013-305690Google Scholar393https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFGhurrM&md5=0f2a785b5222b819e54ed20b2fe414f5Psychological stress and corticotropin-releasing hormone increase intestinal perrneability in humans by a mast cell-dependent mechanismVanuytsel, Tiro; van Wanrooy, Sander; Vanheel, Hanne; Vanormelingen, Christophe; Verschueren, Sofie; Houben, Eis; Rasoel, Shadea Salim; Toth, Joran; Holvoet, Lieselot; Farre, Ricard; Van Oudenhove, Lukas; Boeckxstaens, Guy; Verbeke, Kristin; Tack, JanGut (2014), 63 (8), 1293-1299CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective Intestinal permeability and psychol. stress have been implicated in the pathophysiol. of IBD and IBS. Studies in animals suggest that stress increases permeability via corticotropin-releasing hormone (CRH)-mediated mast cell activation. Our aim was to investigate the effect of stress on intestinal permeability in humans and its underlying mechanisms. Design Small intestinal permeability was quantified by a 2 h lactulose-mannitol urinary excretion test. In a first study, 23 healthy volunteers were subjected to four different conditions: control; indomethacin; public speech and anticipation of electroshocks. In a second study, five test conditions were investigated in 13 volunteers: control; after pretreatment with disodium cromoglycate (DSCG); administration of CRH; DSCG+CRH and DSCG +public speech. Results Indomethacin, as a pos. comparator (0.071±0.040 vs 0.030±0.022; p<0.0001), and public speech (0.059±0.040; p<0.01), but not the shock protocol increased intestinal permeability. Similarly, salivary cortisol was only increased after public speech. Subgroup anal. demonstrated that the effect of public speech on permeability was only present in subjects with a significant elevation of cortisol. CRH increased the lactulose-mannitol ratio (0.042±0.021 vs 0.028±0.009; p=0.02), which was inhibited by the mast cell stabilizer DSCG. Finally, intestinal permeability was unaltered by public speech with DSCG pretreatment. Conclusions Acute psychol. stress increases small intestinal permeability in humans. Peripheral CRH reproduces the effect of stress and DSCG blocks the effect of both stress and CRH, suggesting the involvement of mast cells. These findings provide new insight into the complex interplay between the central nervous system and GI function in man.
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394Yarandi, S. S.; Peterson, D. A.; Treisman, G. J.; Moran, T. H.; Pasricha, P. J. Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases. J. Neurogastroenterol. Motil. 2016, 22, 201– 212, DOI: 10.5056/jnm15146Google Scholar394https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28flslyntg%253D%253D&md5=a8f9435630fc3c88946e23865acf98e3Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and DiseasesYarandi Shadi S; Pasricha Pankaj J; Peterson Daniel A; Treisman Glen J; Moran Timothy HJournal of neurogastroenterology and motility (2016), 22 (2), 201-12 ISSN:2093-0879.Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.
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395Kelly, J. R.; Kennedy, P. J.; Cryan, J. F.; Dinan, T. G.; Clarke, G.; Hyland, N. P. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 2015, 9, 392, DOI: 10.3389/fncel.2015.00392Google Scholar395https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXlvVClt78%253D&md5=5ef019ed88138c8045ffb0f1df040cfdBreaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disordersKelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.Frontiers in Cellular Neuroscience (2015), 9 (), 392/1-392/20CODEN: FCNRAH; ISSN:1662-5102. (Frontiers Media S.A.)The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiol. of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a crit. node within the brain-gut axis. Mounting preclin. evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low grade inflammation obsd. in disorders such as depression and the gut microbiome plays a crit. role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clin. and preclin. evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.
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396Tannock, G. W.; Savage, D. C. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect. Immun. 1974, 9, 591– 598, DOI: 10.1128/iai.9.3.591-598.1974Google Scholar396https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaE2c7itFKhug%253D%253D&md5=37c815abc5ba5dfea79f92d3e98a52d3Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tractTannock G W; Savage D CInfection and immunity (1974), 9 (3), 591-8 ISSN:0019-9567.Aerobic and anaerobic cultural techniques and histological methods were used in a study of the effects of environmental and dietary stress on the indigenous microbiota of the gastrointestinal tract of mice. Mice previously inoculated with Salmonella typhimurium were examined in a similar manner. Three strains of mice (CD-1, Ha/ICr, and C57BL) were used. Control animals previously inoculated with S. typhimurium had low population levels of Salmonella bacteria in the small and large bowel. Mice previously inoculated with Salmonella and then deprived of food, water, and bedding for 48 h harbored high population levels of these bacteria in their small and large bowels. Coliforms increased in numbers in the large bowel of stressed mice inoculated with Salmonella and in the jejunum-ileum and cecum of stressed mice not previously inoculated with Salmonella. Control mice had high population levels of lactobacilli inhabiting the keratinized squamous epithelium of the stomach. Stressed mice showed dramatic reductions in these populations of lactobacilli. Populations of fusiform-shaped bacteria associated with the mucosal epithelium of the cecum and colon in control mice were reduced in stressed mice as determined by microscope examination of histological sections. Total anaerobic counts were similar, however, in both stressed and control animals. Environmental and dietary stress markedly alter the gastrointestinal microbiota in mice. Therefore, such stressful conditions profoundly affect the factors that regulate the localization and population levels of microorganisms in the stomach and intestines.
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397Yang, H.; Zhao, X.; Tang, S.; Huang, H.; Zhao, X.; Ning, Z.; Fu, X.; Zhang, C. Probiotics reduce psychological stress in patients before laryngeal cancer surgery. Asia Pac. J. Clin. Oncol. 2016, 12, e92– 96, DOI: 10.1111/ajco.12120Google ScholarThere is no corresponding record for this reference.
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398Karl, J. P.; Margolis, L. M.; Madslien, E. H.; Murphy, N. E.; Castellani, J. W.; Gundersen, Y.; Hoke, A. V.; Levangie, M. W.; Kumar, R.; Chakraborty, N. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am. J. Physiol. Gastrointest. Liver Physiol. 2017, 312, G559– g571, DOI: 10.1152/ajpgi.00066.2017Google ScholarThere is no corresponding record for this reference.
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399Kato-Kataoka, A.; Nishida, K.; Takada, M.; Kawai, M.; Kikuchi-Hayakawa, H.; Suda, K.; Ishikawa, H.; Gondo, Y.; Shimizu, K.; Matsuki, T. Fermented Milk Containing Lactobacillus casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress. Appl. Environ. Microbiol. 2016, 82, 3649– 3658, DOI: 10.1128/AEM.04134-15Google Scholar399https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVykur3P&md5=0b33c7e6ab05b00969fcbec2f69f0696Fermented milk containing Lactobacillus casei strain shirota preserves the diversity of the gut microbiota and relieves abdominal dysfunction in healthy medical students exposed to academic stressKato-Kataoka, Akito; Nishida, Kensei; Takada, Mai; Kawai, Mitsuhisa; Kikuchi-Hayakawa, Hiroko; Suda, Kazunori; Ishikawa, Hiroshi; Gondo, Yusuke; Shimizu, Kensuke; Matsuki, Takahiro; Kushiro, Akira; Hoshi, Ryoutaro; Watanabe, Osamu; Igarashi, Tomoki; Miyazaki, Kouji; Kuwano, Yuki; Rokutan, KazuhitoApplied and Environmental Microbiology (2016), 82 (12), 3649-3658CODEN: AEMIDF; ISSN:1098-5336. (American Society for Microbiology)Stress-induced abdominal dysfunction is an attractive target for probiotics. To investigate the effects of the probiotic Lactobacillus casei strain Shirota on abdominal dysfunction, a double-blind, placebo-controlled trial was conducted with healthy medical students undertaking an authorized nationwide examn. for academic advancement. For 8 wk, until the day before the examn., 23 and 24 subjects consumed an L. casei strain Shirota-fermented milk and a placebo milk daily, resp. In addn. to assessments of abdominal symptoms, psychophys. state, and salivary stress markers, gene expression changes in peripheral blood leukocytes and compn. of the gut microbiota were analyzed using DNA microarray anal. and 16S rRNA gene amplicon sequence anal., resp., before and after the intervention. Stress-induced increases in a visual analog scale measuring feelings of stress, the total score of abdominal dysfunction, and the no. of genes with changes in expression of more than 2-fold in leukocytes were significantly suppressed in the L. casei strain Shirota group compared with those in the placebo group. A significant increase in salivary cortisol levels before the examn. was obsd. only in the placebo group. The administration of L. casei strain Shirota, but not placebo, significantly reduced gastrointestinal symptoms. Moreover, 16S rRNA gene amplicon sequencing demonstrated that the L. casei strain Shirota group had significantly higher nos. of species, a marker of the alpha-diversity index, in their gut microbiota and a significantly lower percentage of Bacteroidaceae than the placebo group. Our findings indicate that the daily consumption of probiotics, such as L. casei strain Shirota, preserves the diversity of the gut microbiota and may relieve stress-assocd. responses of abdominal dysfunction in healthy subjects exposed to stressful situations.
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400Takada, M.; Nishida, K.; Kataoka-Kato, A.; Gondo, Y.; Ishikawa, H.; Suda, K.; Kawai, M.; Hoshi, R.; Watanabe, O.; Igarashi, T. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterol. Motil. 2016, 28, 1027– 1036, DOI: 10.1111/nmo.12804Google Scholar400https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtVCisr3K&md5=ad973ade1b9aa11673f6276360a96c43Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal modelsTakada, M.; Nishida, K.; Kataoka-Kato, A.; Gondo, Y.; Ishikawa, H.; Suda, K.; Kawai, M.; Hoshi, R.; Watanabe, O.; Igarashi, T.; Kuwano, Y.; Miyazaki, K.; Rokutan, K.Neurogastroenterology & Motility (2016), 28 (7), 1027-1036CODEN: NMOTEK; ISSN:1350-1925. (Wiley-Blackwell)Background : This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. Methods : Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychol. and physiol. stress responses in healthy medical students under academic examn. stress. Subjects received LcS-fermented milk or placebo daily for 8 wk prior to taking a national standardized examn. Subjective anxiety scores, salivary cortisol levels, and the presence of phys. symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 wk, then submitted to water avoidance stress (WAS). Plasma corticosterone concn. and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiol. study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. Key Results : Academic stress-induced increases in salivary cortisol levels and the incidence rate of phys. symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the no. of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. Conclusions & Inferences : These findings suggest that LcS may prevent hypersecretion of cortisol and phys. symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.
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401Zijlmans, M. A.; Korpela, K.; Riksen-Walraven, J. M.; de Vos, W. M.; de Weerth, C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology 2015, 53, 233– 245, DOI: 10.1016/j.psyneuen.2015.01.006Google Scholar401https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MrhtlSntw%253D%253D&md5=7a2cb4bf808aeb6c412cfe6731cc83c5Maternal prenatal stress is associated with the infant intestinal microbiotaZijlmans Maartje A C; de Weerth Carolina; Korpela Katri; Riksen-Walraven J Marianne; de Vos Willem MPsychoneuroendocrinology (2015), 53 (), 233-45 ISSN:.Maternal prenatal stress has been often associated with infant physical development and health, as well as psychological functioning and behavior. However, the mechanisms underlying these relations remain elusive. The goal of the present study was to prospectively investigate the development of the intestinal microbiota as a potential pathway linking maternal prenatal stress and infant health. The development of the infant intestinal microbiota was followed over the first 110 days after birth in a healthy cohort of 56 vaginally born Dutch infants. Additionally, the relation between infant intestinal microbiota and gastrointestinal and allergic symptoms was examined. Results showed that maternal prenatal stress, i.e., either reported stress or elevated basal maternal salivary cortisol concentrations or both, was strongly and persistently associated with the infants' microbiota composition as determined by a phylogenetic microarray. Infants of mothers with high cumulative stress (i.e., high reported stress and high cortisol concentrations) during pregnancy had significantly higher relative abundances of Proteobacterial groups known to contain pathogens (related to Escherichia, Serratia, and Enterobacter), and lower relative abundances of lactic acid bacteria (i.e., Lactobacillus, Lactoccus, Aerococcus) and Bifidobacteria, altogether characteristics of a potentially increased level of inflammation. Furthermore, this aberrant colonization pattern was related to more maternally reported infant gastrointestinal symptoms and allergic reactions. In conclusion, clear links were found between maternal prenatal stress and the infant intestinal microbiota and health. Although causality cannot be concluded, the results suggest a possible mechanism by which maternal prenatal stress influences the offspring development. These results suggest a potential for bacterial interventions to enhance offspring health and development in pregnant women with stress.
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402Naseribafrouei, A.; Hestad, K.; Avershina, E.; Sekelja, M.; Linlo̷kken, A.; Wilson, R.; Rudi, K. Correlation between the human fecal microbiota and depression. Neurogastroenterol. Motil. 2014, 26, 1155– 1162, DOI: 10.1111/nmo.12378Google Scholar402https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cjotlansg%253D%253D&md5=8617b1502f3d8c8a26fc5e9b81b61427Correlation between the human fecal microbiota and depressionNaseribafrouei A; Hestad K; Avershina E; Sekelja M; Linlokken A; Wilson R; Rudi KNeurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (2014), 26 (8), 1155-62 ISSN:.BACKGROUND: Depression is a chronic syndrome with a pathogenesis linked to various genetic, biological, and environmental factors. Several links between gut microbiota and depression have been established in animal models. In humans, however, few correlations have yet been demonstrated. The aim of our work was therefore to identify potential correlations between human fecal microbiota (as a proxy for gut microbiota) and depression. METHODS: We analyzed fecal samples from 55 people, 37 patients, and 18 non-depressed controls. Our analyses were based on data generated by Illumina deep sequencing of 16S rRNA gene amplicons. KEY RESULTS: We found several correlations between depression and fecal microbiota. The correlations, however, showed opposite directions even for closely related Operational Taxonomic Units (OTU's), but were still associated with certain higher order phylogroups. The order Bacteroidales showed an overrepresentation (p = 0.05), while the family Lachnospiraceae showed an underrepresentation (p = 0.02) of OTU's associated with depression. At low taxonomic levels, there was one clade consisting of five OTU's within the genus Oscillibacter, and one clade within Alistipes (consisting of four OTU's) that showed a significant association with depression (p = 0.03 and 0.01, respectively). CONCLUSIONS & INFERENCES: The Oscillibacter type strain has valeric acid as its main metabolic end product, a homolog of neurotransmitter GABA, while Alistipes has previously been shown to be associated with induced stress in mice. In conclusion, the taxonomic correlations detected here may therefore correspond to mechanistic models.
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403Jiang, H.; Ling, Z.; Zhang, Y.; Mao, H.; Ma, Z.; Yin, Y.; Wang, W.; Tang, W.; Tan, Z.; Shi, J. Altered fecal microbiota composition in patients with major depressive disorder. Brain. Behav. Immun. 2015, 48, 186– 194, DOI: 10.1016/j.bbi.2015.03.016Google Scholar403https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MjkvVOrsQ%253D%253D&md5=efccc79e76ef72ca53b2a01088a42434Altered fecal microbiota composition in patients with major depressive disorderJiang Haiyin; Ling Zongxin; Zhang Yonghua; Mao Hongjin; Yin Yan; Tang Wenxin; Tan Zhonglin; Shi Jianfei; Ma Zhanping; Wang Weihong; Li Lanjuan; Ruan BingBrain, behavior, and immunity (2015), 48 (), 186-94 ISSN:.Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.
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404Tillisch, K.; Mayer, E. A.; Gupta, A.; Gill, Z.; Brazeilles, R.; Le Nevé, B.; van Hylckama Vlieg, J. E. T.; Guyonnet, D.; Derrien, M.; Labus, J. S. Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women. Psychosom. Med. 2017, 79, 905– 913, DOI: 10.1097/PSY.0000000000000493Google Scholar404https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjjtVSjug%253D%253D&md5=cf95fddf62483d46ff0bb43092b984e5Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy WomenTillisch Kirsten; Mayer Emeran A; Gupta Arpana; Gill Zafar; Brazeilles Remi; Le Neve Boris; van Hylckama Vlieg Johan E T; Guyonnet Denis; Derrien Muriel; Labus Jennifer SPsychosomatic medicine (2017), 79 (8), 905-913 ISSN:.OBJECTIVE: Brain-gut-microbiota interactions may play an important role in human health and behavior. Although rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive, and social behaviors, there is little translational human evidence to date. In this study, we identify brain and behavioral characteristics of healthy women clustered by gut microbiota profiles. METHODS: Forty women supplied fecal samples for 16S rRNA profiling. Microbial clusters were identified using Partitioning Around Medoids. Functional magnetic resonance imaging was acquired. Microbiota-based group differences were analyzed in response to affective images. Structural and diffusion tensor imaging provided gray matter metrics (volume, cortical thickness, mean curvature, surface area) as well as fiber density between regions. A sparse Partial Least Square-Discrimination Analysis was applied to discriminate microbiota clusters using white and gray matter metrics. RESULTS: Two bacterial genus-based clusters were identified, one with greater Bacteroides abundance (n = 33) and one with greater Prevotella abundance (n = 7). The Prevotella group showed less hippocampal activity viewing negative valences images. White and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2%, respectively. The Prevotella cluster was associated with differences in emotional, attentional, and sensory processing regions. For gray matter, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and the hippocampus. CONCLUSIONS: These results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain, and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior.
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405Pfau, M. L.; Russo, S. J. Peripheral and Central Mechanisms of Stress Resilience. Neurobiol Stress 2015, 1, 66– 79, DOI: 10.1016/j.ynstr.2014.09.004Google Scholar405https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2srjtVCitw%253D%253D&md5=350802b947683c68f598f7d951b74e0cPeripheral and Central Mechanisms of Stress ResiliencePfau Madeline L; Russo Scott JNeurobiology of stress (2015), 1 (), 66-79 ISSN:2352-2895.Viable new treatments for depression and anxiety have been slow to emerge, likely owing to the complex and incompletely understood etiology of these disorders. A budding area of research with great therapeutic promise involves the study of resilience, the adaptive maintenance of normal physiology and behavior despite exposure to marked psychological stress. This phenomenon, documented in both humans and animal models, involves coordinated biological mechanisms in numerous bodily systems, both peripheral and central. In this review, we provide an overview of resilience mechanisms throughout the body, discussing current research in animal models investigating the roles of the neuroendocrine, immune, and central nervous systems in behavioral resilience to stress.
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406Franklin, T. B.; Saab, B. J.; Mansuy, I. M. Neural mechanisms of stress resilience and vulnerability. Neuron 2012, 75, 747– 761, DOI: 10.1016/j.neuron.2012.08.016Google Scholar406https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlSkt7jJ&md5=04d0c42fc745a5e64ed2ab8b129503b4Neural Mechanisms of Stress Resilience and VulnerabilityFranklin, Tamara B.; Saab, Bechara J.; Mansuy, Isabelle M.Neuron (2012), 75 (5), 747-761CODEN: NERNET; ISSN:0896-6273. (Cell Press)Exposure to stressful events can be differently perceived by individuals and can have persistent sequelae depending on the level of stress resilience or vulnerability of each person. The neural processes that underlie such clin. and socially important differences reside in the anatomical, functional, and mol. connectivity of the brain. Recent work has provided novel insight into some of the involved biol. mechanisms that promises to help prevent and treat stress-related disorders. In this review, we focus on causal and mechanistic evidence implicating altered functions and connectivity of the neuroendocrine system, and of hippocampal, cortical, reward, and serotonergic circuits in the establishment and the maintenance of stress resilience and vulnerability. We also touch upon recent findings suggesting a role for epigenetic mechanisms and neurogenesis in these processes and briefly discuss promising avenues of future investigation.
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407Bear, T.; Dalziel, J.; Coad, J.; Roy, N.; Butts, C.; Gopal, P. The Microbiome-Gut-Brain Axis and Resilience to Developing Anxiety or Depression under Stress. Microorganisms 2021, 9, 723, DOI: 10.3390/microorganisms9040723Google Scholar407https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvFygsbnP&md5=ae3d72141ae28d7267f5b0f9ffec9eecThe microbiome-gut-brain axis and resilience to developing anxiety or depression under stressBear, Tracey; Dalziel, Julie; Coad, Jane; Roy, Nicole; Butts, Christine; Gopal, PramodMicroorganisms (2021), 9 (4), 723CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Episodes of depression and anxiety commonly follow the experience of stress, however not everyone who experiences stress develops a mood disorder. Individuals who are able to experience stress without a neg. emotional effect are considered stress resilient. Stress-resilience (and its counterpart stress-susceptibility) are influenced by several psychol. and biol. factors, including the microbiome-gut-brain axis. Emerging research shows that the gut microbiota can influence mood, and that stress is an important variable in this relationship. Stress alters the gut microbiota and plausibly this could contribute to stress-related changes in mood. Most of the reported research has been conducted using animal models and demonstrates a relationship between gut microbiome and mood. The translational evidence from human clin. studies however is rather limited. In this review we examine the microbiome-gut-brain axis research in relation to stress resilience.
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408Li, L. F.; Zou, H. W.; Song, B. L.; Wang, Y.; Jiang, Y.; Li, Z. L.; Niu, Q. H.; Liu, Y. J. Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress. Neuroendocrinology 2023, 113, 563, DOI: 10.1159/000528876Google Scholar408https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXosFGks7s%253D&md5=67aff20b688aeffcb4be5727d0c10449Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat StressLi, Lai-Fu; Zou, Hua-Wei; Song, Bai-Lin; Wang, Yan; Jiang, Yi; Li, Zi-Lin; Niu, Qiu-Hong; Liu, Ying-JuanNeuroendocrinology (2023), 113 (5), 563-576CODEN: NUNDAJ; ISSN:0028-3835. (S. Karger AG)Introduction: Accumulating evidence indicates that abnormalities in the compn. of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. Methods and Results: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compns. in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent expts., we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 wk attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. Conclusions: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.
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409Dinan, T. G.; Stanton, C.; Cryan, J. F. Psychobiotics: a novel class of psychotropic. Biol. Psychiatry 2013, 74, 720– 726, DOI: 10.1016/j.biopsych.2013.05.001Google Scholar409https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptFGktLw%253D&md5=ff4777b31cb75114db2df567eaf8ed5fPsychobiotics: A Novel Class of PsychotropicDinan, Timothy G.; Stanton, Catherine; Cryan, John F.Biological Psychiatry (2013), 74 (10), 720-726CODEN: BIPCBF; ISSN:0006-3223. (Elsevier)A review. Here, we define a psychobiotic as a live organism that, when ingested in adequate amts., produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis. Preclin. evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems. So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where pos. benefits have been reported for a no. of organisms including Bifidobacterium infantis. Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such benefits may be related to the anti-inflammatory actions of certain psychobiotics and a capacity to reduce hypothalamic-pituitary-adrenal axis activity. Results from large scale placebo-controlled studies are awaited.
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410Chattu, V. K.; Manzar, M. D.; Kumary, S.; Burman, D.; Spence, D. W.; Pandi-Perumal, S. R. The Global Problem of Insufficient Sleep and Its Serious Public Health Implications. Healthcare 2019, 7, 1, DOI: 10.3390/healthcare7010001Google ScholarThere is no corresponding record for this reference.
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411Irwin, C.; McCartney, D.; Desbrow, B.; Khalesi, S. Effects of probiotics and paraprobiotics on subjective and objective sleep metrics: a systematic review and meta-analysis. Eur. J. Clin. Nutr. 2020, 74, 1536– 1549, DOI: 10.1038/s41430-020-0656-xGoogle Scholar411https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38vpsVymtw%253D%253D&md5=4bf85a14c79b5fa2362c983b78c24c6dEffects of probiotics and paraprobiotics on subjective and objective sleep metrics: a systematic review and meta-analysisIrwin Christopher; Desbrow Ben; Irwin Christopher; McCartney Danielle; Khalesi SamanEuropean journal of clinical nutrition (2020), 74 (11), 1536-1549 ISSN:.Inadequate sleep (i.e., duration and/or quality) is becoming increasingly recognized as a global public health issue. Interaction via the gut-brain axis suggests that modification of the gut microbial environment via supplementation with live microorganisms (probiotics) or nonviable microorganisms/microbial cell fractions (paraprobiotics) may improve sleep health. This systematic review and meta-analysis aimed to clarify the effect of consuming probiotics/paraprobiotics on subjective and objective sleep metrics. Online databases were searched from 1980 to October 2019 for studies involving adults who consumed probiotics or paraprobiotics in controlled trials, during which, changes in subjective and/or objective sleep parameters were examined. A total of 14 studies (20 trials) were included in meta-analysis. Random effects meta-analyses indicated that probiotics/paraprobiotics supplementation significantly reduced Pittsburgh Sleep Quality Index (PSQI) score (i.e., improved sleep quality) relative to baseline (-0.78-points, 95% confidence interval: 0.395-1.166; p < 0.001). No significant effect was found for changes on other subjective sleep scales, nor objective parameters of sleep (efficiency/latency) measured using polysomnography or actigraphy. Subgroup analysis for PSQI data suggested that the magnitude of the effect was greater (although not statistically) in healthy participants than those with a medical condition, when treatment contained a single (rather than multiple) strain of probiotic bacteria, and when the duration of treatment was ≥8 weeks. Probiotics/paraprobiotics supplementation may have some efficacy in improving perceived sleep health, measured using the PSQI. While current evidence does not support a benefit of consuming probiotics/paraprobiotics when measured by other subjective sleep scales, nor objective measures of sleep; more studies using well-controlled, within-subject experimental designs are needed.
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412Smith, R. P.; Easson, C.; Lyle, S. M.; Kapoor, R.; Donnelly, C. P.; Davidson, E. J.; Parikh, E.; Lopez, J. V.; Tartar, J. L. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One 2019, 14, e0222394 DOI: 10.1371/journal.pone.0222394Google Scholar412https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1SitbzI&md5=df4265f4dc5ab89d8e8d5ea3aeeaf61dGut microbiome diversity is associated with sleep physiology in humansSmith, Robert P.; Easson, Cole; Lyle, Sarah M.; Kapoor, Ritishka; Donnelly, Chase P.; Davidson, Eileen J.; Parikh, Esha; Lopez, Jose V.; Tartar, Jaime L.PLoS One (2019), 14 (10), e0222394CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that the gut microbiome can influence sleep quality. Previous studies that have examd. sleep deprivation and the human gut microbiome have yielded conflicting results. A recent study found that sleep deprivation leads to changes in gut microbiome compn. while a different study found that sleep deprivation does not lead to changes in gut microbiome. Accordingly, the relationship between sleep physiol. and the gut microbiome remains unclear. To address this uncertainty, we used actigraphy to quantify sleep measures coupled with gut microbiome sampling to det. how the gut microbiome correlates with various measures of sleep physiol. We measured immune system biomarkers and carried out a neurobehavioral assessment as these variables might modify the relationship between sleep and gut microbiome compn. We found that total microbiome diversity was pos. correlated with increased sleep efficiency and total sleep time, and was neg. correlated with wake after sleep onset. We found pos. correlations between total microbiome diversity and interleukin-6, a cytokine previously noted for its effects on sleep. Anal. of microbiome compn. revealed that within phyla richness of Bacteroidetes and Firmicutes were pos. correlated with sleep efficiency, interleukin-6 concns. and abstr. thinking. Finally, we found that several taxa (Lachnospiraceae, Corynebacterium, and Blautia) were neg. correlated with sleep measures. Our findings initiate linkages between gut microbiome compn., sleep physiol., the immune system and cognition. They may lead to mechanisms to improve sleep through the manipulation of the gut microbiome.
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413Benedict, C.; Vogel, H.; Jonas, W.; Woting, A.; Blaut, M.; Schürmann, A.; Cedernaes, J. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Molecular Metabolism 2016, 5, 1175– 1186, DOI: 10.1016/j.molmet.2016.10.003Google Scholar413https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslKksbnO&md5=8574818ba82e517a8811c2d448e71218Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individualsBenedict, Christian; Vogel, Heike; Jonas, Wenke; Woting, Anni; Blaut, Michael; Schurmann, Annette; Cedernaes, JonathanMolecular Metabolism (2016), 5 (12), 1175-1186CODEN: MMOEAS; ISSN:2212-8778. (Elsevier GmbH)Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown.In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-wt. men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02:45-07:00 h), and after two nights of normal sleep (NS; sleep opportunity 22:30-07:00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addn., participants underwent an oral glucose tolerance test following each sleep intervention.Microbiota compn. anal. (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes:Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P < 0.05) - previously all assocd. with metabolic perturbations in animal or human models. However, no PSD vs. NS effect on beta diversity or on fecal short-chain fatty acid concns. was found. Fasting and postprandial insulin sensitivity decreased after PSD vs. NS (all P < 0.05).Our findings demonstrate that short-term sleep loss induces subtle effects on human microbiota. To what extent the obsd. changes to the microbial community contribute to metabolic consequences of sleep loss warrants further investigations in larger and more prolonged sleep studies, to also assess how sleep loss impacts the microbiota in individuals who already are metabolically compromised.
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414Zhang, S. L.; Bai, L.; Goel, N.; Bailey, A.; Jang, C. J.; Bushman, F. D.; Meerlo, P.; Dinges, D. F.; Sehgal, A. Human and rat gut microbiome composition is maintained following sleep restriction. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, E1564– E1571, DOI: 10.1073/pnas.1620673114Google Scholar414https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitlGjtb4%253D&md5=9aec22e0fd2e866919821f3abfd6a440Human and rat gut microbiome composition is maintained following sleep restrictionZhang, Shirley L.; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J.; Bushman, Frederic D.; Meerlo, Peter; Dinges, David F.; Sehgal, AmitaProceedings of the National Academy of Sciences of the United States of America (2017), 114 (8), E1564-E1571CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is assocd. with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurol. and cognitive impairments. Shifts in gut microbiome compn. have also been assocd. with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examd. the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or compn. induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.
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415Anderson, J. R.; Carroll, I.; Azcarate-Peril, M. A.; Rochette, A. D.; Heinberg, L. J.; Peat, C.; Steffen, K.; Manderino, L. M.; Mitchell, J.; Gunstad, J. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults. Sleep Med. 2017, 38, 104– 107, DOI: 10.1016/j.sleep.2017.07.018Google Scholar415https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7gs1Krug%253D%253D&md5=0d012c9192a94fefff439edbf9f374deA preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adultsAnderson Jason R; Rochette Amber D; Manderino Lisa M; Carroll Ian; Azcarate-Peril M Andrea; Heinberg Leslie J; Peat Christine; Steffen Kristine; Mitchell James; Gunstad JohnSleep medicine (2017), 38 (), 104-107 ISSN:.OBJECTIVES: Inadequate sleep increases the risk for age-related cognitive decline and recent work suggests a possible role of the gut microbiota in this phenomenon. Partial sleep deprivation alters the human gut microbiome, and its composition is associated with cognitive flexibility in animal models. Given these findings, we examined the possible relationship among the gut microbiome, sleep quality, and cognitive flexibility in a sample of healthy older adults. METHODS: Thirty-seven participants (age 64.59 ± 7.54 years) provided a stool sample for gut microbial sequencing and completed the Pittsburgh Sleep Quality Index and Stroop Color Word Test as part of a larger project. RESULTS: Better sleep quality was associated with better Stroop performance and higher proportions of the gut microbial phyla Verrucomicrobia and Lentisphaerae. Stroop Word and Color-Word performance correlated with higher proportions of Verrucomicrobia and Lentisphaerae. Partial correlations suggested that the relationship between Lentisphaerae and Stroop Color-Word performance was better accounted for by sleep quality; sleep quality remained a significant predictor of Color-Word performance, independent of the Lentisphaerae proportion, while the relationship between Lentisphaerae and Stroop performance was non-significant. Verrucomicrobia and sleep quality were not associated with Stroop Word performance independent of one another. CONCLUSIONS: The current findings suggest a possible relationship among sleep quality, composition of the gut microbiome, and cognitive flexibility in healthy older adults. Prospective and experimental studies are needed to confirm these findings and determine whether improving microbiome health may buffer against sleep-related cognitive decline in older adults.
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416Krueger, J. M.; Opp, M. R. Sleep and Microbes. Int. Rev. Neurobiol. 2016, 131, 207– 225, DOI: 10.1016/bs.irn.2016.07.003Google Scholar416https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsV2gsLvJ&md5=dad2798ad92da44ed4d1658a5ccf585aSleep and microbesKrueger, J. M.; Opp, M. R.International Review of Neurobiology (2016), 131 (Gut Microbiome and Behavior), 207-225CODEN: IRNEAE; ISSN:0074-7742. (Elsevier)Sleep is profoundly altered during the course of infectious diseases. The typical response to infection includes an initial increase in nonrapid eye movement sleep (NREMS) followed by an inhibition in NREMS. REMS is inhibited during infections. Bacterial cell wall components, such as peptidoglycan and lipopolysaccharide, macrophage digests of these components, such as muramyl peptides, and viral products, such as viral double-stranded RNA, trigger sleep responses. They do so via pathogen-assocd. mol. pattern recognition receptors that, in turn, enhance cytokine prodn. Altered sleep and assocd. sleep-facilitated fever responses are likely adaptive responses to infection. Normal sleep in physiol. conditions may also be influenced by gut microbes because the microbiota is affected by circadian rhythms, stressors, diet, and exercise. Furthermore, sleep loss enhances translocation of viable bacteria from the intestine, which provides another means by which sleep-microbe interactions impact neurobiol.
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417Frey, D. J.; Fleshner, M.; Wright, K. P. The effects of 40 h of total sleep deprivation on inflammatory markers in healthy young adults. Brain, Behavior, and Immunity 2007, 21, 1050– 1057, DOI: 10.1016/j.bbi.2007.04.003Google Scholar417https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFSlsb3K&md5=37547bb61f385800507b6d12ba696a28The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adultsFrey, Danielle J.; Fleshner, Monika; Wright, Kenneth P.Brain, Behavior, and Immunity (2007), 21 (8), 1050-1057CODEN: BBIMEW; ISSN:0889-1591. (Elsevier B.V.)Inflammatory cytokines are released in response to stress, tissue damage, and infection. Acutely, this response is adaptive; however, chronic elevation of inflammatory proteins can contribute to health problems including cardiovascular, endocrine, mood, and sleep disorders. Few studies have examd. how sleep deprivation acutely affects inflammatory markers, which was the aim of the current study. Nineteen healthy men and women aged 28.05 ± 8.56 (mean ± SD) were totally sleep deprived for 40 h under const. routine conditions. Pro-inflammatory markers: intracellular adhesion mol.-1 (ICAM-1), E-selectin, vascular adhesion mol.-1 (VCAM-1), c-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) were assayed in plasma. Daytime levels during baseline (hours 1-15 of scheduled wakefulness) were compared to daytime levels during sleep deprivation (hours 25-39 of scheduled wakefulness), thus controlling for circadian phase within an individual. Repeated measures ANOVA with planned comparisons showed that 40 h of total sleep deprivation induced a significant increase in E-selectin, ICAM-1, IL-1β, and IL-1ra, a significant decrease in CRP and IL-6, and no significant change in VCAM-1. Alterations in circulating levels of pro- and anti-inflammatory cytokines and cell adhesion mols. during sleep deprivation were consistent with both increased and decreased inflammation. These findings suggest that one night of sleep loss triggers a stress response that includes stimulation of both pro- and anti-inflammatory proteins in the healthy young subjects tested under our exptl. conditions.
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418Kamada, N.; Seo, S. U.; Chen, G. Y.; Núñez, G. Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 2013, 13, 321– 335, DOI: 10.1038/nri3430Google Scholar418https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmsFahsr0%253D&md5=6b2f2776e4d63244ddc52296b78a7e3eRole of the gut microbiota in immunity and inflammatory diseaseKamada, Nobuhiko; Seo, Sang-Uk; Chen, Grace Y.; Nunez, GabrielNature Reviews Immunology (2013), 13 (5), 321-335CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. The mammalian intestine is colonized by trillions of microorganisms, most of which are bacteria that have co-evolved with the host in a symbiotic relationship. The collection of microbial populations that reside on and in the host is commonly referred to as the microbiota. A principal function of the microbiota is to protect the intestine against colonization by exogenous pathogens and potentially harmful indigenous microorganisms via several mechanisms, which include direct competition for limited nutrients and the modulation of host immune responses. Conversely, pathogens have developed strategies to promote their replication in the presence of competing microbiota. Breakdown of the normal microbial community increases the risk of pathogen infection, the overgrowth of harmful pathobionts and inflammatory disease. Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.
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419Yasuda, M.; Kato, S.; Yamanaka, N.; Iimori, M.; Matsumoto, K.; Utsumi, D.; Kitahara, Y.; Amagase, K.; Horie, S.; Takeuchi, K. 5-HT3 receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cells. Br. J. Pharmacol. 2013, 168, 1388– 1400, DOI: 10.1111/bph.12019Google Scholar419https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjvVWqsbw%253D&md5=4b61c17a5f35e37d17fe4b1c046082625-HT3 receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cellsYasuda, M.; Kato, S.; Yamanaka, N.; Iimori, M.; Matsumoto, K.; Utsumi, D.; Kitahara, Y.; Amagase, K.; Horie, S.; Takeuchi, K.British Journal of Pharmacology (2013), 168 (6), 1388-1400CODEN: BJPCBM; ISSN:1476-5381. (Wiley-Blackwell)Background and Purpose Chemotherapeutic agents, including 5-fluorouracil (5-FU), frequently cause intestinal mucositis resulting in severe diarrhoea and morphol. mucosal damage. 5-HT3 receptor antagonists are clin. effective in the treatment of nausea and emesis during cancer chemotherapy. Therefore we here have examd. the effects of 5-HT3 receptor antagonists on 5-FU-induced intestinal mucositis in mice. Exptl. Approach Intestinal mucositis was induced in male C57BL/6 mice by daily administration of 5-FU (50 mg·kg-1) for 5 days. Effects of 5-HT3 receptor antagonists, ramosetron (0.01-0.1 mg·kg-1) and ondansetron (5 mg·kg-1), on the accompanying histol., cytokine prodn. and apoptosis were assessed. Key Results Continuous administration of 5-FU to mice caused severe intestinal mucositis, which was histol. characterized by the shortening of villi and destruction of intestinal crypts, accompanied by body wt. loss and diarrhoea. Daily ramosetron administration dose-dependently reduced the severity of intestinal mucositis, body wt. loss and diarrhoea. Similar beneficial effects were obsd. with ondansetron. The no. of apoptotic, caspase-3- and caspase-8-activated cells increased 24 h after the first 5-FU administration, and these responses were reduced by ramosetron. The up-regulation of TNF-α, IL-1β and IL-6 following 5-FU treatment was also attenuated by ramosetron. Conclusions and Implications 5-HT3 receptor antagonists ameliorated 5-FU-induced intestinal mucositis in mice, and this action could result from suppression of apoptotic responses in the intestinal crypt cells via inhibition of cytokine expression. Thus, 5-HT3 receptor antagonists may be useful for preventing not only nausea and emesis but also intestinal mucositis during 5-FU chemotherapy.
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420Li, H.-L.; Lu, L.; Wang, X.-S.; Qin, L.-Y.; Wang, P.; Qiu, S.-P.; Wu, H.; Huang, F.; Zhang, B.-B.; Shi, H.-L. Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis. Frontiers in Cellular and Infection Microbiology 2017, 7, 455, DOI: 10.3389/fcimb.2017.00455Google Scholar420https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVOksLjN&md5=49a68aba1109c9d7c48bea4be7ef51b3Alteration of gut microbiota and inflammatory cytokine/chemokine profiles in 5-fluorouracil induced intestinal mucositisLi, Hong-Li; Lu, Lan; Wang, Xiao-Shuang; Qin, Li-Yue; Wang, Ping; Qiu, Shui-Ping; Wu, Hui; Huang, Fei; Zhang, Bei-Bei; Shi, Hai-Lian; Wu, Xiao-JunFrontiers in Cellular and Infection Microbiology (2017), 7 (), 455/1-455/14CODEN: FCIMAB; ISSN:2235-2988. (Frontiers Media S.A.)Disturbed homeostasis of gut microbiota has been suggested to be closely assocd. with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by wt. loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion mols. such as vascular cell adhesion mol.-1 (VCAM-1), intercellular adhesion mol.-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion mol.-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body wt. loss and colon shortening of 5-Fu treated mice. In addn., the fecal transplant from 5-Fu treated mice reduced body wt. and colon length of vancomycinpretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathol. process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.
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421Benton, D.; Williams, C.; Brown, A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 2007, 61, 355– 361, DOI: 10.1038/sj.ejcn.1602546Google Scholar421https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2s7ivVChtg%253D%253D&md5=53506d17e623536e3f6080844c41d60eImpact of consuming a milk drink containing a probiotic on mood and cognitionBenton D; Williams C; Brown AEuropean journal of clinical nutrition (2007), 61 (3), 355-61 ISSN:0954-3007.OBJECTIVE: The impact on mood and memory of consuming a probiotic containing milk drink, or a placebo, was examined as, previously, a poor mood has been found to correlate with the frequency of constipation. DESIGN: A double-blind placebo-controlled trial with random allocation of subjects. SETTING: Subjects went about their normal life in the community apart from three visits to the laboratory. SUBJECTS: One hundred and thirty-two healthy members of general population, mean age 61.8 years, volunteered in response to local media coverage. One hundred and twenty-four finished the trial. INTERVENTION: For a 3-week period, either a probiotic containing milk drink, or a placebo, were consumed daily. Mood and cognition were measured at baseline, and after 10 and 20 days of consumption. RESULTS: At baseline those who reported themselves to be less frequently constipated were more clearheaded, confident and elated. Although the taking of the probiotic did not generally change the mood, this appeared to be a reflection of the generally good mood in this sample. When those in the bottom third of the depressed/elated dimension at baseline were considered, they selectively responded by reporting themselves as happy rather than depressed after taking the probiotic. The intervention did not, however, influence the reported frequency of defaecation, probably a reflection of the initially low incidence of constipation. An unexpected and possibly chance finding was that the consumption of probiotics resulted in a slightly-poorer performance on two measures of memory. CONCLUSIONS: The consumption of a probiotic-containing yoghurt improved the mood of those whose mood was initially poor. This improvement in mood was not, however, associated with an increased frequency of defaecation.
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422Parkar, S. G.; Kalsbeek, A.; Cheeseman, J. F. Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health. Microorganisms 2019, 7, 41, DOI: 10.3390/microorganisms7020041Google Scholar422https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWntbbN&md5=38628e871023dc23d7f7a6421abf671bPotential role for the gut microbiota in modulating host circadian rhythms and metabolic healthParkar, G.; Kalsbeek, Andries; Cheeseman, James F.Microorganisms (2019), 7 (2), 41CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)This article reviews the current evidence assocg. gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of compn., their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivs., vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased prodn. of hydrogen sulfide and the resultant decreased prodn. of butyrate, in turn affect substrate oxidn. and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome assocd. with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis.
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423Zhao, D.; Yu, Y.; Shen, Y.; Liu, Q.; Zhao, Z.; Sharma, R.; Reiter, R. J. Melatonin Synthesis and Function: Evolutionary History in Animals and Plants. Front. Endocrinol. 2019, 10, 249, DOI: 10.3389/fendo.2019.00249Google Scholar423https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7is1Grug%253D%253D&md5=40cfef92a222457727f1c2af3d4e39b8Melatonin Synthesis and Function: Evolutionary History in Animals and PlantsZhao Dake; Zhao Dake; Zhao Dake; Yu Yang; Zhao Zhiwei; Shen Yong; Liu Qin; Sharma Ramaswamy; Reiter Russel JFrontiers in endocrinology (2019), 10 (), 249 ISSN:1664-2392.Melatonin is an ancient molecule that can be traced back to the origin of life. Melatonin's initial function was likely that as a free radical scavenger. Melatonin presumably evolved in bacteria; it has been measured in both α-proteobacteria and in photosynthetic cyanobacteria. In early evolution, bacteria were phagocytosed by primitive eukaryotes for their nutrient value. According to the endosymbiotic theory, the ingested bacteria eventually developed a symbiotic association with their host eukaryotes. The ingested α-proteobacteria evolved into mitochondria while cyanobacteria became chloroplasts and both organelles retained their ability to produce melatonin. Since these organelles have persisted to the present day, all species that ever existed or currently exist may have or may continue to synthesize melatonin in their mitochondria (animals and plants) and chloroplasts (plants) where it functions as an antioxidant. Melatonin's other functions, including its multiple receptors, developed later in evolution. In present day animals, via receptor-mediated means, melatonin functions in the regulation of sleep, modulation of circadian rhythms, enhancement of immunity, as a multifunctional oncostatic agent, etc., while retaining its ability to reduce oxidative stress by processes that are, in part, receptor-independent. In plants, melatonin continues to function in reducing oxidative stress as well as in promoting seed germination and growth, improving stress resistance, stimulating the immune system and modulating circadian rhythms; a single melatonin receptor has been identified in land plants where it controls stomatal closure on leaves. The melatonin synthetic pathway varies somewhat between plants and animals. The amino acid, tryptophan, is the necessary precursor of melatonin in all taxa. In animals, tryptophan is initially hydroxylated to 5-hydroxytryptophan which is then decarboxylated with the formation of serotonin. Serotonin is either acetylated to N-acetylserotonin or it is methylated to form 5-methoxytryptamine; these products are either methylated or acetylated, respectively, to produce melatonin. In plants, tryptophan is first decarboxylated to tryptamine which is then hydroxylated to form serotonin.
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424Wang, B.; Duan, R.; Duan, L. Prevalence of sleep disorder in irritable bowel syndrome: A systematic review with meta-analysis. Saudi J. Gastroenterol. 2018, 24, 141, DOI: 10.4103/sjg.SJG_603_17Google Scholar424https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MjitlKquw%253D%253D&md5=730bd07cbe5b513966dc95fae89e40b2Prevalence of sleep disorder in irritable bowel syndrome: A systematic review with meta-analysisWang Ben; Duan Ruqiao; Duan LipingSaudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association (2018), 24 (3), 141-150 ISSN:.Background/Aims: We conducted this meta-analysis to evaluate the prevalence of sleep disorder in irritable bowel syndrome (IBS) patients and study the association between IBS and sleep disorder. Materials and Methods: A systematic search was conducted by searching PubMed, Embase, and Cochrane library databases using the following search terms: "functional gastrointestinal disorders," "Sleep disturbance," "Sleep disorder," "insomnia," "Dysomnias," "irritable bowel syndrome," and "IBS." Studies evaluating the association between IBS and sleep disorder were identified. Data analysis was conducted using meta-analysis software Comprehensive Meta-Analysis (CMA) 2.0. Heterogeneity across studies was evaluated by χ(2)and I(2)statistics. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Sensitivity analysis was also performed by removing each single study separately. Results: The bibliographical search yielded a total of 2866 studies. Finally, 36 studies including 63620 participants were identified. The prevalence of sleep disorder in IBS was 37.6% (95% CI: 31.4% to 44.3%) based on this meta-analysis. The pooled odds ratio was 2.618 (95% CI: 2.052% to 3.341). Publication bias was not determined. Regarding the sensitivity analysis, the outcome was stable regardless of which study was removed. Conclusions: The prevalence of sleep disorder was higher in IBS compared to healthy controls and may be associated with the pathogenesis of IBS. The prevalence of sleep disorder in IBS may differ according to different areas, age, gender, occupation, and IBS diagnostic criteria. Further studies are needed to investigate any possible causal relationship between sleep disorder and IBS.
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425Miglis, M. G. Autonomic dysfunction in primary sleep disorders. Sleep Med. 2016, 19, 40– 49, DOI: 10.1016/j.sleep.2015.10.001Google Scholar425https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s%252FhsVGruw%253D%253D&md5=fd1b77b45703f3d7f7fff9a04148062dAutonomic dysfunction in primary sleep disordersMiglis Mitchell GSleep medicine (2016), 19 (), 40-9 ISSN:.The autonomic nervous system plays an important role in the coordination of many important physiologic functions during sleep. Many patients with untreated sleep disorders will describe symptoms of autonomic impairment, and a majority of patients with autonomic impairment have some form of sleep disorder. This article will explore possible explanations for this connection, as well as review the current literature on autonomic impairment in common primary sleep disorders including obstructive sleep apnea, insomnia, restless legs syndrome, periodic limb movement disorder, narcolepsy, and rapid eye movement sleep behavior disorder.
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426Tobaldini, E.; Costantino, G.; Solbiati, M.; Cogliati, C.; Kara, T.; Nobili, L.; Montano, N. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases. Neurosci Biobehav Rev. 2017, 74, 321– 329, DOI: 10.1016/j.neubiorev.2016.07.004Google Scholar426https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7osFOhuw%253D%253D&md5=bc2e172ba1b6eb6934d79334fb29fe4eSleep, sleep deprivation, autonomic nervous system and cardiovascular diseasesTobaldini Eleonora; Costantino Giorgio; Solbiati Monica; Cogliati Chiara; Kara Tomas; Nobili Lino; Montano NicolaNeuroscience and biobehavioral reviews (2017), 74 (Pt B), 321-329 ISSN:.Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.
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427Vgontzas, A. N.; Chrousos, G. P. Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. Endocrinol. Metab. Clin. North Am. 2002, 31, 15– 36, DOI: 10.1016/S0889-8529(01)00005-6Google Scholar427https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XkvFensL8%253D&md5=fbdba5b68852ab87b1f623ab49876c40Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disordersVgontzas, Alexandros N.; Chrousos, George P.Endocrinology and Metabolism Clinics of North America (2002), 31 (1), 15-36CODEN: ECNAER; ISSN:0889-8529. (W. B. Saunders Co.)A review. Sleep has an inhibitory effect on the hypothalamic-pituitary-adrenal (HPA) axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is assocd. with a 24-h increase of corticotropin (ACTH) and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. The proinflammatory cytokines IL-6 and TNF-α are increased in disorders assocd. with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia.
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428Schlereth, T.; Birklein, F. The sympathetic nervous system and pain. Neuromolecular Med. 2008, 10, 141– 147, DOI: 10.1007/s12017-007-8018-6Google Scholar428https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXpslSmu7g%253D&md5=aa6a85237f078eb184444d2422b85457The Sympathetic Nervous System and PainSchlereth, Tanja; Birklein, FrankNeuroMolecular Medicine (2008), 10 (3), 141-147CODEN: NMEEAN; ISSN:1535-1084. (Humana Press Inc.)The sympathetic nervous system (SNS) and pain interact on many levels of the neuraxis. In healthy subjects, activation of the SNS in the brain usually suppresses pain mainly by descending inhibition of nociceptive transmission in the spinal cord. Furthermore, some exptl. data even suggest that the SNS might control peripheral inflammation and nociceptive activation. However, even subtle changes in pathophysiol. can dramatically change the effect of SNS on pain, and vice versa. In the periphery, inflammation or nociceptive activation is enhanced, spinal descending inhibition is reversed to spinal facilitation, and finally the awareness of all these changes will induce anxiety, which furthermore amplifies pain perception, affects pain behavior, and depresses mood. Unraveling the detailed mol. mechanisms of how this interaction of SNS and pain is established in health and disease will help us to treat pain more successfully in the future.
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429Wong, R. K.; Yang, C.; Song, G. H.; Wong, J.; Ho, K. Y. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study. Dig. Dis. Sci. 2015, 60, 186– 194, DOI: 10.1007/s10620-014-3299-8Google Scholar429https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlanur%252FI&md5=d79ff1de2d0caca527789357176d18d6Melatonin Regulation as a Possible Mechanism for Probiotic (VSL#3) in Irritable Bowel Syndrome: A Randomized Double-Blinded Placebo StudyWong, Reuben K.; Yang, Cao; Song, Guang-Hui; Wong, Jennie; Ho, Khek-YuDigestive Diseases and Sciences (2015), 60 (1), 186-194CODEN: DDSCDJ; ISSN:0163-2116. (Springer)Background: Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. Aim: The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychol. and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. Methods: Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 wk. Subjects completed bowel and psychol. questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. Results: Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. Conclusions: VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin prodn., hence modulating IBS symptoms, in individuals with a normal circadian rhythm.
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430Zhao, E.; Tait, C.; Minacapelli, C. D.; Catalano, C.; Rustgi, V. K. Circadian Rhythms, the Gut Microbiome, and Metabolic Disorders. Gastro Hep Advances 2022, 1, 93– 105, DOI: 10.1016/j.gastha.2021.10.008Google ScholarThere is no corresponding record for this reference.
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431Liang, X.; Bushman, F. D.; FitzGerald, G. A. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc. Natl. Acad. Sci. U. S. A. 2015, 112, 10479– 10484, DOI: 10.1073/pnas.1501305112Google Scholar431https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1ygt7bP&md5=21b0d86495276282bf024e7bebab44d3Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clockLiang, Xue; Bushman, Frederic D.; FitzGerald, Garret A.Proceedings of the National Academy of Sciences of the United States of America (2015), 112 (33), 10479-10484CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)In mammals, multiple physiol., metabolic, and behavioral processes are subject to circadian rhythms, adapting to changing light in the environment. Here we analyzed circadian rhythms in the fecal microbiota of mice using deep sequencing, and found that the abs. amt. of fecal bacteria and the abundance of Bacteroidetes exhibited circadian rhythmicity, which was more pronounced in female mice. Disruption of the host circadian clock by deletion of Bmal1, a gene encoding a core mol. clock component, abolished rhythmicity in the fecal microbiota compn. in both genders. Bmal1 deletion also induced alterations in bacterial abundances in feces, with differential effects based on sex. Thus, although host behavior, such as time of feeding, is of recognized importance, here we show that sex interacts with the host circadian clock, and they collectively shape the circadian rhythmicity and compn. of the fecal microbiota in mice.
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432Paulose, J. K.; Wright, J. M.; Patel, A. G.; Cassone, V. M. Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity. PLoS One 2016, 11, e0146643 DOI: 10.1371/journal.pone.0146643Google Scholar432https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisVKgu78%253D&md5=66c63528753d2603bd2d71785a8ee81cHuman gut bacteria are sensitive to melatonin and express endogenous circadian rhythmicityPaulose, Jiffin K.; Wright, John M.; Patel, Akruti G.; Cassone, Vincent M.PLoS One (2016), 11 (1), e0146643/1-e0146643/13CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Circadian rhythms are fundamental properties of most eukaryotes, but evidence of biol. clocks that drive these rhythms in prokaryotes has been restricted to Cyanobacteria. In vertebrates, the gastrointestinal system expresses circadian patterns of gene expression, motility and secretion in vivo and in vitro, and recent studies suggest that the enteric microbiome is regulated by the host's circadian clock. However, it is not clear how the host's clock regulates the microbiome. Here, we demonstrate at least one species of commensal bacterium from the human gastrointestinal system, Enterobacter aerogenes, is sensitive to the neurohormone melatonin, which is secreted into the gastrointestinal lumen, and expresses circadian patterns of swarming and motility. Melatonin specifically increases the magnitude of swarming in cultures of E. aerogenes, but not in Escherichia coli or Klebsiella pneumoniae. The swarming appears to occur daily, and transformation of E. aerogenes with a flagellar motor-protein driven lux plasmid confirms a temp.-compensated circadian rhythm of luciferase activity, which is synchronized in the presence of melatonin. Altogether, these data demonstrate a circadian clock in a non-cyanobacterial prokaryote and suggest the human circadian system may regulate its microbiome through the entrainment of bacterial clocks.
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433Mukherji, A.; Kobiita, A.; Ye, T.; Chambon, P. Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 2013, 153, 812– 827, DOI: 10.1016/j.cell.2013.04.020Google Scholar433https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsFSmtb0%253D&md5=92e774e6925c70c2bf0ba544d0d0f8e2Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRsMukherji, Atish; Kobiita, Ahmad; Ye, Tao; Chambon, PierreCell (Cambridge, MA, United States) (2013), 153 (4), 812-827CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Alterations of symbiosis between microbiota and intestinal epithelial cells (IEC) are assocd. with intestinal and systemic pathologies. Interactions between bacterial products (MAMPs) and Toll-like receptors (TLRs) are known to be mandatory for IEC homeostasis, but how TLRs may time homeostatic functions with circadian changes is unknown. Our functional and mol. dissections of the IEC circadian clock demonstrate that its integrity is required for microbiota-IEC dialog. In IEC, the antiphasic expression of the RORα activator and RevErbα repressor clock output regulators generates a circadian rhythmic TLR expression that converts the temporally arrhythmic microbiota signaling into circadian rhythmic JNK and IKKβ activities, which prevents RevErbα activation by PPARα that would disrupt the circadian clock. Moreover, through activation of AP1 and NF-κB, these activities, together with RORα and Rev-Erbα, enable timing homeostatic functions of numerous genes with IEC circadian events. Interestingly, microbiota signaling deficiencies induce a prediabetic syndrome due to ileal corticosterone overprodn. consequent to clock disruption.
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434Paschos, G. K.; FitzGerald, G. A. Circadian Clocks and Metabolism: Implications for Microbiome and Aging. Trends Genet. 2017, 33, 760– 769, DOI: 10.1016/j.tig.2017.07.010Google Scholar434https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1ygu7rO&md5=7484d224885089e3d0ab0afd749b7e09Circadian Clocks and Metabolism: Implications for Microbiome and AgingPaschos, Georgios K.; FitzGerald, Garret A.Trends in Genetics (2017), 33 (10), 760-769CODEN: TRGEE2; ISSN:0168-9525. (Elsevier Ltd.)The circadian clock directs many aspects of metab., to sep. in time opposing metabolic pathways and optimize metabolic efficiency. The master circadian clock of the suprachiasmatic nucleus synchronizes to light, while environmental cues such as temp. and feeding, out of phase with the light schedule, may synchronize peripheral clocks. This misalignment of central and peripheral clocks may be involved in the development of disease and the acceleration of aging, possibly in a gender-specific manner. Here we discuss the interplay between the circadian clock and metab., the importance of the microbiome, and how they relate to aging.
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435Fernandez-Real, J. M.; Serino, M.; Blasco, G.; Puig, J.; Daunis-i-Estadella, J.; Ricart, W.; Burcelin, R.; Fernández-Aranda, F.; Portero-Otin, M. Gut Microbiota Interacts With Brain Microstructure and Function. J. Clin Endocrinol Metab 2015, 100, 4505– 4513, DOI: 10.1210/jc.2015-3076Google Scholar435https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XjtlSntr0%253D&md5=0cc5aed4e2adb94468aa404d91f622caGut microbiota interacts with brain microstructure and functionFernandez-Real, Jose-Manuel; Serino, Matteo; Blasco, Gerard; Puig, Josep; Daunis-i-Estadella, Josep; Ricart, Wifredo; Burcelin, Remy; Fernandez-Aranda, Fernando; Portero-Otin, ManuelJournal of Clinical Endocrinology and Metabolism (2015), 100 (12), 4505-4513CODEN: JCEMAZ; ISSN:0021-972X. (Endocrine Society)Context: Evidence from animals suggests that gut microbiota affects brain structure and function but evidence in humans is scarce. Objective: This study sought to evaluate potential interactions among gut microbiota compn., brain microstructure, and cognitive tests in obese and nonobese subjects. Design, Setting, and Participants: This was a cross-sectional study at a tertiary hospital including 20 consecutive obese and 19 nonobese subjects similar in age and sex. Main Outcome Measures: Gut microbiota (16S bacterial gene pyrosequencing), brain microstructure (diffusion tensor imaging of brain white and gray matter and R2* sequences in magnetic resonance imaging) and cognitive tests. Results: Hierarchical clustering revealed a specific gut microbiota-brain map profile for obese individuals who could be discriminated from nonobese subjects (accuracy of 0.81). Strikingly, Shannon index was linked to R2* and fractional anisotropy of the hypothalamus, caudate nucleus, and hippocampus, suggesting sparing of these brain structures with increased bacterial biodiversity. Microbiota profile also clustered with cognitive function. The relative abundance of Actinobacteria phylum was linked not only to magnetic resonance imaging diffusion tensor imaging variables in the thalamus, hypothalamus, and amygdala but also to cognitive test scores related to speed, attention, and cognitive flexibility. Conclusions: In sum, obesity status affects microbiota-brain microstructure and function crosstalk.
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436Carlson, A. L.; Xia, K.; Azcarate-Peril, M. A.; Goldman, B. D.; Ahn, M.; Styner, M. A.; Thompson, A. L.; Geng, X.; Gilmore, J. H.; Knickmeyer, R. C. Infant Gut Microbiome Associated With Cognitive Development. Biol. Psychiatry 2018, 83, 148– 159, DOI: 10.1016/j.biopsych.2017.06.021Google Scholar436https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cfmtFKhug%253D%253D&md5=da5db5d0f67c9c3f8f710957f5098af7Infant Gut Microbiome Associated With Cognitive DevelopmentCarlson Alexander L; Xia Kai; Gilmore John H; Azcarate-Peril M Andrea; Goldman Barbara D; Ahn Mihye; Styner Martin A; Thompson Amanda L; Geng Xiujuan; Knickmeyer Rebecca CBiological psychiatry (2018), 83 (2), 148-159 ISSN:.BACKGROUND: Studies in rodents provide compelling evidence that microorganisms inhabiting the gut influence neurodevelopment. In particular, experimental manipulations that alter intestinal microbiota impact exploratory and communicative behaviors and cognitive performance. In humans, the first years of life are a dynamic time in gut colonization and brain development, but little is known about the relationship between these two processes. METHODS: We tested whether microbial composition at 1 year of age is associated with cognitive outcomes using the Mullen Scales of Early Learning and with global and regional brain volumes using structural magnetic resonance imaging at 1 and 2 years of age. Fecal samples were collected from 89 typically developing 1-year-olds. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. RESULTS: Cluster analysis identified 3 groups of infants defined by their bacterial composition. Mullen scores at 2 years of age differed significantly between clusters. In addition, higher alpha diversity was associated with lower scores on the overall composite score, visual reception scale, and expressive language scale at 2 years of age. Exploratory analyses of neuroimaging data suggest the gut microbiome has minimal effects on regional brain volumes at 1 and 2 years of age. CONCLUSIONS: This is the first study to demonstrate associations between the gut microbiota and cognition in human infants. As such, it represents an essential first step in translating animal data into the clinic.
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437Polidano, C.; Zhu, A.; Bornstein, J. C. The relation between cesarean birth and child cognitive development. Sci. Rep. 2017, 7, 11483, DOI: 10.1038/s41598-017-10831-yGoogle Scholar437https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cbnvFCnug%253D%253D&md5=51bd54f42e44da3394ee875c78c1bab4The relation between cesarean birth and child cognitive developmentPolidano Cain; Zhu Anna; Bornstein Joel CScientific reports (2017), 7 (1), 11483 ISSN:.This is the first detailed study of the relation between cesarean birth and child cognitive development. We measure differences in child cognitive performance at 4 to 9 years of age between cesarean-born and vaginally-born children (n = 3,666) participating in the Longitudinal Study of Australian Children (LSAC). LSAC is a nationally representative birth cohort surveyed biennially. Using multivariate regression, we control for a large range of confounders related to perinatal risk factors and the socio-economic advantage associated with cesarean-born children. Across several measures, we find that cesarean-born children perform significantly below vaginally-born children, by up to a tenth of a standard deviation in national numeracy test scores at age 8-9. Estimates from a low-risk sub-sample and lower-bound analysis suggest that the relation is not spuriously related to unobserved confounding. Lower rates of breastfeeding and adverse child and maternal health outcomes that are associated with cesarean birth are found to explain less than a third of the cognitive gap, which points to the importance of other mechanisms such as disturbed gut microbiota. The findings underline the need for a precautionary approach in responding to requests for a planned cesarean when there are no apparent elevated risks from vaginal birth.
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438Chung, Y.-C.; Jin, H.-M.; Cui, Y.; Kim, D. S.; Jung, J. M.; Park, J.-I.; Jung, E.-S.; Choi, E.-K.; Chae, S.-W. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J. Funct. Foods 2014, 10, 465– 474, DOI: 10.1016/j.jff.2014.07.007Google Scholar438https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlamsrnL&md5=ab84d274bb605567faa4570a68a5e4a0Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adultsChung, Young-Chul; Jin, Hong-Mei; Cui, Yin; Kim, Dal Sik; Jung, Jin Mu; Park, Jong-Il; Jung, Eun-Soo; Choi, Eun-Kyung; Chae, Soo-WanJournal of Functional Foods (2014), 10 (), 465-474CODEN: JFFOAX; ISSN:1756-4646. (Elsevier Ltd.)Probiotics are consumed in a wide variety of fermented foods to improve health. This study was conducted to investigate the effects of Lactobacillus helveticus-fermented milk (LHFM), on cognitive function in healthy older adults. A 12-wk, double-blind, randomized controlled expt. was conducted. Cognitive tests (neuropsychol. and cognitive fatigue) and measurements of the perceived stress scale (PSS), geriatric depression scale-short form (GDS-SF), brain-derived neurotrophic factor (BDNF) and whole blood viscosity (WBV) were conducted before and after the expt. The administration of LHFM for 12 wk in healthy older adults produced improvement on cognitive tests compared to the placebo group. However, no significant effects were obsd. for PSS, GDS-SF, BDNF, and WBV. Thus, consumption of LHFM might be beneficial for improving cognitive function.
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439Tillisch, K.; Labus, J.; Kilpatrick, L.; Jiang, Z.; Stains, J.; Ebrat, B.; Guyonnet, D.; Legrain-Raspaud, S.; Trotin, B.; Naliboff, B. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 2013, 144, 1394– 1401.e4, DOI: 10.1053/j.gastro.2013.02.043Google Scholar439https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntV2hsbc%253D&md5=8e502d60712e23b3d1c4a0f95ced0dbdConsumption of Fermented Milk Product With Probiotic Modulates Brain ActivityTillisch, Kirsten; Labus, Jennifer; Kilpatrick, Lisa; Jiang, Zhiguo; Stains, Jean; Ebrat, Bahar; Guyonnet, Denis; Legrain Raspaud, Sophie; Trotin, Beatrice; Naliboff, Bruce; Mayer, Emeran A.Gastroenterology (2013), 144 (7), 1394-1401.e4CODEN: GASTAB; ISSN:0016-5085. (Elsevier)Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 wk by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 wk. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed.FMPP intake was assocd. with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) contg. affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was assocd. with changes in midbrain connectivity, which could explain the obsd. differences in activity during the task. Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation.
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440Smith, A. P.; Sutherland, D.; Hewlett, P. An Investigation of the Acute Effects of Oligofructose-Enriched Inulin on Subjective Wellbeing, Mood and Cognitive Performance. Nutrients 2015, 7, 8887– 8896, DOI: 10.3390/nu7115441Google Scholar440https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVKitrvF&md5=0216a2d1e0dd330812f879fcd3e0b822An investigation of the acute effects of oligofructose-enriched inulin on subjective wellbeing, mood and cognitive performanceSmith, Andrew P.; Sutherland, David; Hewlett, PaulNutrients (2015), 7 (11), 8887-8896CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)Inulin is a natural food component found in many plants that are part of the human diet (e.g., leeks, onions, wheat, garlic, chicory and artichokes). It is added to many foods and is used to increase dietary fiber, replace fats or carbohydrates, and as a prebiotic (a stimulant of beneficial bacteria in the colon). Oligofructose, which is also present in these foods, produces similar effects and most research has used a combination of these products. A previous study (Smith, 2005) investigated the effects of regular consumption of oligofructose-enriched inulin on wellbeing, mood, and cognitive performance in humans. The results showed that oligofructose-enriched inulin had no neg. effects but that it did not improve wellbeing, mood, or performance. The aim of the present study was to examine the acute effects of oligofructose-enriched inulin (5 g) over a 4 h period during which the participants remained in the lab. A double blind placebo (maltodextrin) controlled study (N = 47) was carried out with the order of conditions being counterbalanced and the two sessions a week apart. On each test day mood and cognitive performance were assessed at baseline (at 8:00) and then following inulin or placebo (at 11:00). Prior to the second test session (at 10:30) participants completed a questionnaire assessing their phys. symptoms and mental health during the test morning. The inulin and placebo were provided in powder form in 5 g sachets. Volunteers consumed one sachet in decaffeinated tea or decaffeinated coffee with breakfast (9:00). Questionnaire results showed that on the day that the inulin was consumed, participants felt happier, had less indigestion and were less hungry than when they consumed the placebo. As for performance and mood tasks, the most consistent effects were on the episodic memory tasks where consumption of inulin was assocd. with greater accuracy on a recognition memory task, and improved recall performance (immediate and delayed). Further research is required to identify the mechanisms that underlie this effect with glucose metab. being one candidate.
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441Lee, S.-H.; Yoon, S.-H.; Jung, Y.; Kim, N.; Min, U.; Chun, J.; Choi, I. Emotional well-being and gut microbiome profiles by enterotype. Sci. Rep. 2020, 10, 20736, DOI: 10.1038/s41598-020-77673-zGoogle Scholar441https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFShtrvP&md5=b631f1f52bec181eadc3b0aa7bcb82d4Emotional well-being and gut microbiome profiles by enterotypeLee, Sung-Ha; Yoon, Seok-Hwan; Jung, Yeonjae; Kim, Namil; Min, Uigi; Chun, Jongsik; Choi, IncheolScientific Reports (2020), 10 (1), 20736CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: With increasing attention being paid to improving emotional well-being, recent evidence points to gut microbiota as a key player in regulating mental and phys. health via bidirectional communication between the brain and gut. Here, we examine the assocn. between emotional well-being and gut microbiome profiles (i.e., gut microbiome compn., diversity, and the moderating role of the enterotypes) among healthy Korean adults (n = 83, mean age = 48.9, SD = 13.2). The research was performed using high-throughput 16S rRNA gene sequencing to obtain gut microbiome profiles, as well as a self-report survey that included the Pos. Affect Neg. Affect Schedule (PANAS). The cluster-based anal. identified two enterotypes dominated by the genera Bacteroides (n = 49) and Prevotella (n = 34). Generalized linear regression anal. reveals significant assocns. between pos. emotion and gut microbiome diversity (Shannon Index) among participants in the Prevotella dominant group, whereas no such relationship emerged among participants in the Bacteroides group. Moreover, a novel genus from the family Lachnospiraceae is assocd. with emotional well-being scores, both pos. and neg. Together, the current findings highlight the enterotype-specific links between the gut microbiota community and emotion in healthy adults and suggest the possible roles of the gut microbiome in promoting mental health.
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442Gros, D. F.; Antony, M. M.; McCabe, R. E.; Swinson, R. P. Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depression. J. Anxiety Disord. 2009, 23, 290– 296, DOI: 10.1016/j.janxdis.2008.08.004Google Scholar442https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M3htVWktQ%253D%253D&md5=5d733c6bb4cb72b961aedf020212c1f2Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depressionGros Daniel F; Antony Martin M; McCabe Randi E; Swinson Richard PJournal of anxiety disorders (2009), 23 (2), 290-6 ISSN:.High rates of irritable bowel syndrome (IBS) symptoms have been reported in individuals diagnosed with anxiety and depressive disorders. However, most studies have investigated these relations in a single disorder, rather than a heterogeneous group of patients, thereby not allowing for comparisons across anxiety disorders and depression, or for considering the effects of comorbidity. Thus, the present study investigated the symptoms of IBS in a diverse group of patients (N=357) by administering questionnaires and a diagnostic interview. A high frequency of IBS symptoms was found in patients with panic disorder, generalized anxiety disorder, and major depressive disorder. However, the frequency of IBS symptoms in patients with social anxiety disorder, specific phobia, and obsessive-compulsive disorder was comparable to rates found in community samples. In addition, anxiety sensitivity and illness attitudes and intrusiveness were predictive of elevated IBS symptomatology. Together, these findings emphasize the role physiological symptoms of anxiety and worry in the co-occurrence of the anxiety disorders and IBS.
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443Mayer, E. A.; Labus, J. S.; Tillisch, K.; Cole, S. W.; Baldi, P. Towards a systems view of IBS. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 592– 605, DOI: 10.1038/nrgastro.2015.121Google Scholar443https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVartb%252FO&md5=f4e08efb2d474e9dd01e6d651bc10d9dTowards a systems view of IBSMayer, Emeran A.; Labus, Jennifer S.; Tillisch, Kirsten; Cole, Steven W.; Baldi, PierreNature Reviews Gastroenterology & Hepatology (2015), 12 (10), 592-605CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)Despite an extensive body of reported information about peripheral and central mechanisms involved in the pathophysiol. of IBS symptoms, no comprehensive disease model has emerged that would guide the development of novel, effective therapies. In this Review, we will first describe novel insights into some key components of brain-gut interactions, starting with the emerging findings of distinct functional and structural brain signatures of IBS. We will then point out emerging correlations between these brain networks and genomic, gastrointestinal, immune and gut-microbiome-related parameters. We will incorporate this new information, as well as the reported extensive literature on various peripheral mechanisms, into a systems-based disease model of IBS, and discuss the implications of such a model for improved understanding of the disorder, and for the development of more-effective treatment approaches in the future.
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444Zhang, J.; Ma, L.; Chang, L.; Pu, Y.; Qu, Y.; Hashimoto, K. A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration. Translational Psychiatry 2020, 10, 186, DOI: 10.1038/s41398-020-00878-3Google Scholar444https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFemurzK&md5=61f60452ccdbade0de95b7c628eb1bcbA key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administrationZhang, Jiancheng; Ma, Li; Chang, Lijia; Pu, Yaoyu; Qu, Youge; Hashimoto, KenjiTranslational Psychiatry (2020), 10 (1), 186CODEN: TPRSCF; ISSN:2158-3188. (Nature Research)Abstr.: The vagus nerve plays a role in the cross talk between the brain and gut microbiota, which could be involved in depression. The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Here, we investigated the effects of subdiaphragmatic vagotomy (SDV) on the depression-like phenotype and the abnormal compn. of gut microbiota in mice after lipopolysaccharide (LPS) administration. LPS caused a depression-like phenotype, inflammation, increase in spleen wt., and downregulation of synaptic proteins in the medial prefrontal cortex (mPFC) in the sham-operated mice. In contrast, LPS did not produce a depression-like phenotype and downregulated synaptic proteins in the mPFC after SDV. The spleen wt. and plasma levels of pro-inflammatory cytokines in the SDV + LPS group were lower than those of the sham + LPS group. Interestingly, there were pos. correlations between the plasma levels of pro-inflammatory cytokines and spleen wt., suggesting a relationship between inflammatory events and spleen wt. Furthermore, LPS led to significant alterations in gut microbiota diversity in sham-operated mice, but not SDV-operated mice. In an unweighted UniFrac PCoA, the dots representing the sham + LPS group were located far away from the dots representing the other three groups. Our results suggest that LPS produces a depression-like phenotype, increases spleen wt., triggers inflammation, downregulates synaptic proteins in the mPFC, and leads to abnormal compn. of gut microbiota via the subdiaphragmatic vagus nerve. It is likely that the vagus nerve plays a crucial role in the brain-gut-microbiota axis.
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445Pu, Y.; Tan, Y.; Qu, Y.; Chang, L.; Wang, S.; Wei, Y.; Wang, X.; Hashimoto, K. A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes. Brain, Behavior, and Immunity 2021, 94, 318– 326, DOI: 10.1016/j.bbi.2020.12.032Google Scholar445https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXks1GmsLg%253D&md5=6fa3a523797005c53ffaae8eeadd5e13A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypesPu, Yaoyu; Tan, Yunfei; Qu, Youge; Chang, Lijia; Wang, Siming; Wei, Yan; Wang, Xingming; Hashimoto, KenjiBrain, Behavior, and Immunity (2021), 94 (), 318-326CODEN: BBIMEW; ISSN:0889-1591. (Elsevier Inc.)The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) regulates the cholinergic ascending anti-inflammatory pathway involved in depression. We previously reported that Chrna7 knock-out (KO) mice show depression-like phenotypes through systemic inflammation. In this study, we investigated whether fecal microbiota transplantation (FMT) from Chrna7 KO mice causes depression-like phenotypes in mice treated with an antibiotic cocktail (ABX). Chrna7 KO mice with depression-like phenotypes show an abnormal gut microbiota compn., although the alpha diversity and beta diversity were not altered. FMT from Chrna7 KO mice caused depression-like phenotypes, systemic inflammation, and downregulation of synaptic proteins in the prefrontal cortex (PFC) in the ABX-treated mice compared to FMT from the control mice. The Principal component anal. based on the OTU level showed that the FMT group from the KO mice were different from the FMT group from the control mice. We found differences in abundance for several bacteria in the FMT group from the KO mice at the taxonomic level when compared with the other group. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of depression-like phenotypes in the ABX-treated mice after FMT from Chrna7 KO mice. These data suggest that FMT from Chrna7 KO mice produce depression-like phenotypes in ABX-treated mice via the subdiaphragmatic vagus nerve. The brain-gut-microbiota axis assocn. with the subdiaphragmatic vagus nerve plays an important role in the development of depression.
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446Bruch, J. D. Intestinal infection associated with future onset of an anxiety disorder: Results of a nationally representative study. Brain. Behav. Immun. 2016, 57, 222– 226, DOI: 10.1016/j.bbi.2016.05.014Google Scholar446https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s%252FjtFGhsA%253D%253D&md5=c7c22b1e692bd2dad0e5d60738023742Intestinal infection associated with future onset of an anxiety disorder: Results of a nationally representative studyBruch Joseph DBrain, behavior, and immunity (2016), 57 (), 222-226 ISSN:.Recent research involving mice suggests a possible relationship between intestinal infection and future anxiety-like behavior. However, there has been little epidemiological research showing such a connection in humans. This study uses the Medical Expenditure Panel Survey (MEPS) to assess longitudinally the association between intestinal infection and later onset of an anxiety disorder, through a nationally representative sample. Six 2-year panel datasets, each comprised of 5 consecutive rounds, were pooled from 2007 to 2013 to gather records for all respondents 18years of age or older that did not have an anxiety disorder in Round 1 (n=63, 133 people). Within the study sample, there were 2577 individuals with an intestinal infection in Round 1 and 4239 individuals with an anxiety disorder that began in Round 2, 3, 4, or 5. Overall, intestinal infection in Round 1 was associated with a 1.34 (P<0.01) odds ratio of having an anxiety disorder that began in Round 2, 3, 4, or 5. Separate analyses were performed to determine whether the association applied to other infection types, including respiratory infection, urinary tract infection, hepatitis infection, and skin infection. Respiratory infection was associated with a 1.36 (P<0.01) odds ratio of having an anxiety disorder that began in Round 2, 3, 4, or 5; no other infection type showed a significant association. More research on human populations is needed to examine the apparent association and explore potential mechanisms by which gut pathogens might influence anxiety.
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447Kiecolt-Glaser, J. K.; Wilson, S. J.; Shrout, M. R.; Madison, A. A.; Andridge, R.; Peng, J.; Malarkey, W. B.; Bailey, M. T. The gut reaction to couples’ relationship troubles: A route to gut dysbiosis through changes in depressive symptoms. Psychoneuroendocrinology 2021, 125, 105132, DOI: 10.1016/j.psyneuen.2021.105132Google Scholar447https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXktFygtL8%253D&md5=e9c4ae7fed44cf1523cdc8ec6b5cc329The gut reaction to couples' relationship troubles: A route to gut dysbiosis through changes in depressive symptomsKiecolt-Glaser, Janice K.; Wilson, Stephanie J.; Shrout, M. Rosie; Madison, Annelise A.; Andridge, Rebecca; Peng, Juan; Malarkey, William B.; Bailey, Michael T.Psychoneuroendocrinology (2021), 125 (), 105132CODEN: PSYCDE; ISSN:0306-4530. (Elsevier Ltd.)The gut microbiota plays a role in a wide range of diseases and disorders, with low microbial diversity and richness emerging as notable risk factors. This longitudinal study addressed the impact of marital quality (assessed by the Couples Satisfaction Index) on changes in depressive symptoms, and gut diversity, richness, and permeability. On two occasions an av. of 90 days apart, 162 people provided stool and blood samples, and completed questionnaires. Depressive symptoms, assessed by the Center for Epidemiol. Studies Depression Scale (CES-D), increased from visit 1 to visit 2 in those with clin. significant relationship problems, in contrast to the lack of change among their more satisfied counterparts. These changes in depression were consequential: the gut microbiota's diversity and richness decreased in tandem with the increase in depressive symptoms. Lower relationship satisfaction also foreshadowed increases in lipopolysaccharide binding protein from visit 1 to visit 2, reflecting greater translocation of bacterial endotoxin from the gut to blood circulation, a process that fuels inflammation. Lower diversity and richness provide a pathway from depressive symptoms and marital distress to subsequent health risk.
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448Kim, H. N.; Yun, Y.; Ryu, S.; Chang, Y.; Kwon, M. J.; Cho, J.; Shin, H.; Kim, H. L. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain. Behav. Immun. 2018, 69, 374– 385, DOI: 10.1016/j.bbi.2017.12.012Google Scholar448https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1Mzlt1ChsQ%253D%253D&md5=d42ed7e6a1ec1dbc0c9b0433cec20765Correlation between gut microbiota and personality in adults: A cross-sectional studyKim Han-Na; Yun Yeojun; Ryu Seungho; Chang Yoosoo; Kwon Min-Jung; Cho Juhee; Shin Hocheol; Kim Hyung-LaeBrain, behavior, and immunity (2018), 69 (), 374-385 ISSN:.Personality affects fundamental behavior patterns and has been related with health outcomes and mental disorders. Recent evidence has emerged supporting a relationship between the microbiota and behavior, referred to as brain-gut relationships. Here, we first report correlations between personality traits and gut microbiota. This research was performed using the Revised NEO Personality Inventory and the sequencing data of the 16S rRNA gene in 672 adults. The diversity and the composition of the human gut microbiota exhibited significant difference when stratified by personality traits. We found that personality traits were significantly correlated with diversity of gut microbiota, while their differences were extremely subtle. High neuroticism and low conscientiousness groups were correlated with high abundance of Gammaproteobacteria and Proteobacteria, respectively when covariates, including age, sex, BMI and nutrient intake, were controlled. Additionally, high conscientiousness group also showed increased abundance of some universal butyrate-producing bacteria including Lachnospiraceae. This study was of observational and cross-sectional design and our findings must be further validated through metagenomic or metatranscriptomic methodologies, or metabolomics-based analyses. Our findings will contribute to elucidating potential links between the gut microbiota and personality, and provide useful insights toward developing and testing personality- and microbiota-based interventions for promoting health.
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449Valles-Colomer, M.; Falony, G.; Darzi, Y.; Tigchelaar, E. F.; Wang, J.; Tito, R. Y.; Schiweck, C.; Kurilshikov, A.; Joossens, M.; Wijmenga, C. The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology 2019, 4, 623– 632, DOI: 10.1038/s41564-018-0337-xGoogle Scholar449https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmtFKhsbo%253D&md5=7cda15fafdf7111f9a9b90136944511fThe neuroactive potential of the human gut microbiota in quality of life and depressionValles-Colomer, Mireia; Falony, Gwen; Darzi, Youssef; Tigchelaar, Ettje F.; Wang, Jun; Tito, Raul Y.; Schiweck, Carmen; Kurilshikov, Alexander; Joossens, Marie; Wijmenga, Cisca; Claes, Stephan; Van Oudenhove, Lukas; Zhernakova, Alexandra; Vieira-Silva, Sara; Raes, JeroenNature Microbiology (2019), 4 (4), 623-632CODEN: NMAICH; ISSN:2058-5276. (Nature Research)The relationship between gut microbial metab. and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota-gut-brain communication has mostly been explored in animal models, with human research lagging behind. Large-scale metagenomics studies could facilitate the translational process, but their interpretation is hampered by a lack of dedicated ref. databases and tools to study the microbial neuroactive potential. Surveying a large microbiome population cohort (Flemish Gut Flora Project, n = 1,054) with validation in independent data sets (ntotal = 1,070), we studied how microbiome features correlate with host quality of life and depression. Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently assocd. with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants. Using a module-based anal. framework, we assembled a catalog of neuroactive potential of sequenced gut prokaryotes. Gut-brain module anal. of fecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating pos. with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid prodn. in depression. Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.
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450Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D. R.; Fernandes, G. R.; Tap, J.; Bruls, T.; Batto, J.-M. Enterotypes of the human gut microbiome. Nature 2011, 473, 174– 180, DOI: 10.1038/nature09944Google Scholar450https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkvFeisLo%253D&md5=3f8dfb6b1250d9d913e9ecd03984d9d7Enterotypes of the human gut microbiomeArumugam, Manimozhiyan; Raes, Jeroen; Pelletier, Eric; Le Paslier, Denis; Yamada, Takuji; Mende, Daniel R.; Fernandes, Gabriel R.; Tap, Julien; Bruls, Thomas; Batto, Jean-Michel; Bertalan, Marcelo; Borruel, Natalia; Casellas, Francesc; Fernandez, Leyden; Gautier, Laurent; Hansen, Torben; Hattori, Masahira; Hayashi, Tetsuya; Kleerebezem, Michiel; Kurokawa, Ken; Leclerc, Marion; Levenez, Florence; Manichanh, Chaysavanh; Nielsen, H. Bjorn; Nielsen, Trine; Pons, Nicolas; Poulain, Julie; Qin, Junjie; Sicheritz-Ponten, Thomas; Tims, Sebastian; Torrents, David; Ugarte, Edgardo; Zoetendal, Erwin G.; Wang, Jun; Guarner, Francisco; Pedersen, Oluf; de Vos, Willem M.; Brunak, Soren; Dore, Joel; Weissenbach, Jean; Ehrlich, S. Dusko; Bork, Peer; Antolin, Maria; Artiguenave, Francois; Blottiere, Herve M.; Almeida, Mathieu; Brechot, Christian; Cara, Carlos; Chervaux, Christian; Cultrone, Antonella; Delorme, Christine; Denariaz, Gerard; Dervyn, Rozenn; Foerstner, Konrad U.; Friss, Carsten; van de Guchte, Maarten; Guedon, Eric; Haimet, Florence; Huber, Wolfgang; van Hylckama-Vlieg, Johan; Jamet, Alexandre; Juste, Catherine; Kaci, Ghalia; Knol, Jan; Lakhdari, Omar; Layec, Severine; Le Roux, Karine; Maguin, Emmanuelle; Merieux, Alexandre; Melo Minardi, Raquel; M'rini, Christine; Muller, Jean; Oozeer, Raish; Parkhill, Julian; Renault, Pierre; Rescigno, Maria; Sanchez, Nicolas; Sunagawa, Shinichi; Torrejon, Antonio; Turner, Keith; Vandemeulebrouck, Gaetana; Varela, Encarna; Winogradsky, Yohanan; Zeller, GeorgNature (London, United Kingdom) (2011), 473 (7346), 174-180CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Our knowledge of species and functional compn. of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced fecal metagenomes of individuals from four countries with previously published data sets, the authors identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. They also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited no. of well balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species compn., but abundant mol. functions are not necessarily provided by abundant species, highlighting the importance of a functional anal. to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the obsd. enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
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451Costello, E. K.; Lauber, C. L.; Hamady, M.; Fierer, N.; Gordon, J. I.; Knight, R. Bacterial community variation in human body habitats across space and time. Science 2009, 326, 1694– 1697, DOI: 10.1126/science.1177486Google Scholar451https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFGmsL7K&md5=bc016e97bdcd143c0d46e2b8d496953bBacterial Community Variation in Human Body Habitats Across Space and TimeCostello, Elizabeth K.; Lauber, Christian L.; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I.; Knight, RobScience (Washington, DC, United States) (2009), 326 (5960), 1694-1697CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Elucidating the biogeog. of bacterial communities on the human body is crit. for establishing healthy baselines from which to detect differences assocd. with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in seven to nine healthy adults on four occasions. We found that community compn. was detd. primarily by body habitat. Within habitats, interpersonal variability was high, whereas individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time; such trends may ultimately reveal how microbiome changes cause or prevent disease.
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452Wu, G. D.; Chen, J.; Hoffmann, C.; Bittinger, K.; Chen, Y. Y.; Keilbaugh, S. A.; Bewtra, M.; Knights, D.; Walters, W. A.; Knight, R. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011, 334, 105– 108, DOI: 10.1126/science.1208344Google Scholar452https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Gms77K&md5=da31735ba897d48e54758aeba1dfa913Linking Long-Term Dietary Patterns with Gut Microbial EnterotypesWu, Gary D.; Chen, Jun; Hoffmann, Christian; Bittinger, Kyle; Chen, Ying-Yu; Keilbaugh, Sue A.; Bewtra, Meenakshi; Knights, Dan; Walters, William A.; Knight, Rob; Sinha, Rohini; Gilroy, Erin; Gupta, Kernika; Baldassano, Robert; Nessel, Lisa; Li, Hongzhe; Bushman, Frederic D.; Lewis, James D.Science (Washington, DC, United States) (2011), 334 (6052), 105-108CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Diet strongly affects human health, partly by modulating gut microbiome compn. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly assocd. with long-term diets, particularly protein and animal fat (Bacteroides) vs. carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome compn. changed detectably within 24 h of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are assocd. with long-term diet.
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453Akkasheh, G.; Kashani-Poor, Z.; Tajabadi-Ebrahimi, M.; Jafari, P.; Akbari, H.; Taghizadeh, M.; Memarzadeh, M. R.; Asemi, Z.; Esmaillzadeh, A. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition 2016, 32, 315– 320, DOI: 10.1016/j.nut.2015.09.003Google Scholar453https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVeit7vO&md5=82bddd5d934e0e3ff75ab0ce7a4315aeClinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trialAkkasheh, Ghodarz; Kashani-Poor, Zahra; Tajabadi-Ebrahimi, Maryam; Jafari, Parvaneh; Akbari, Hossein; Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Asemi, Zatollah; Esmaillzadeh, AhmadNutrition (New York, NY, United States) (2016), 32 (3), 315-320CODEN: NUTRER; ISSN:0899-9007. (Elsevier Inc.)We are aware of no study examg. the effects of probiotic supplementation on symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). The present study was designed to det. the effects of probiotic intake on symptoms of depression and metabolic status in patients with MDD. This randomized, double-blind, placebo-controlled clin. trial included 40 patients with a diagnosis of MDD based on DSM-IV criteria whose age ranged between 20 and 55 y. Patients were randomly allocated into two groups to receive either probiotic supplements (n = 20) or placebo (n = 20) for 8 wk. Probiotic capsule consisted of three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 109 CFU/g), Lactobacillus casei (2 × 109 CFU/g), and Bifidobacterium bifidum (2 × 109 CFU/g). Fasting blood samples were taken at the beginning and end of the trial to quantify the relevant variables. All participants provided three dietary records (two weekdays and one weekend) and three phys. activity records during the intervention. Dietary intake of study participants was not significantly different between the two groups. After 8 wk of intervention, patients who received probiotic supplements had significantly decreased Beck Depression Inventory total scores (-5.7 ± 6.4 vs. -1.5 ± 4.8, P = 0.001) compared with the placebo. In addn., significant decreases in serum insulin levels (-2.3 ± 4.1 vs. 2.6 ± 9.3 μIU/mL, P = 0.03), homeostasis model assessment of insulin resistance (-0.6 ± 1.2 vs. 0.6 ± 2.1, P = 0.03), and serum hs-CRP concns. (-1138.7 ± 2274.9 vs. 188.4 ± 1455.5 ng/mL, P = 0.03) were obsd. after the probiotic supplementation compared with the placebo. Addnl., taking probiotics resulted in a significant rise in plasma total glutathione levels (1.8 ± 83.1 vs. -106.8 ± 190.7 μmol/L, P = 0.02) compared with the placebo. We did not find any significant change in fasting plasma glucose, homeostatic model assessment of beta cell function, quant. insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels. Probiotic administration in patients with MDD for 8 wk had beneficial effects on Beck Depression Inventory, insulin, homeostasis model assessment of insulin resistance, hs-CRP concns., and glutathione concns., but did not influence fasting plasma glucose, homeostatic model assessment of beta cell function, quant. insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels.
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454Wallace, C. J. K.; Milev, R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann. Gen. Psychiatry 2017, 16, 14, DOI: 10.1186/s12991-017-0138-2Google Scholar454https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czgvVSjtA%253D%253D&md5=3f6e3576cc50f596843b164ec596e6c1The effects of probiotics on depressive symptoms in humans: a systematic reviewWallace Caroline J K; Milev RoumenAnnals of general psychiatry (2017), 16 (), 14 ISSN:1744-859X.BACKGROUND: Patients suffering from depression experience significant mood, anxiety, and cognitive symptoms. Currently, most antidepressants work by altering neurotransmitter activity in the brain to improve these symptoms. However, in the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the "gut-brain axis." Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. The aim of this review is to analyze the current body of research assessing the effects of probiotics, on symptoms of depression in humans. METHODS: A systematic search of five databases was performed and study selection was completed using the preferred reporting items for systematic reviews and meta-analyses process. RESULTS: Ten studies met criteria and were analyzed for effects on mood, anxiety, and cognition. Five studies assessed mood symptoms, seven studies assessed anxiety symptoms, and three studies assessed cognition. The majority of the studies found positive results on all measures of depressive symptoms; however, the strain of probiotic, the dosing, and duration of treatment varied widely and no studies assessed sleep. CONCLUSION: The evidence for probiotics alleviating depressive symptoms is compelling but additional double-blind randomized control trials in clinical populations are warranted to further assess efficacy.
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455Le Morvan de Sequeira, C.; Hengstberger, C.; Enck, P.; Mack, I. Effect of Probiotics on Psychiatric Symptoms and Central Nervous System Functions in Human Health and Disease: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 621, DOI: 10.3390/nu14030621Google ScholarThere is no corresponding record for this reference.
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456Hill, C.; Guarner, F.; Reid, G.; Gibson, G. R.; Merenstein, D. J.; Pot, B.; Morelli, L.; Canani, R. B.; Flint, H. J.; Salminen, S. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology 2014, 11, 506– 514, DOI: 10.1038/nrgastro.2014.66Google Scholar456https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cfgs12ktQ%253D%253D&md5=471aa530d7d01da3fe859068ed919d75Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probioticHill Colin; Guarner Francisco; Reid Gregor; Gibson Glenn R; Merenstein Daniel J; Pot Bruno; Morelli Lorenzo; Canani Roberto Berni; Flint Harry J; Salminen Seppo; Calder Philip C; Sanders Mary EllenNature reviews. Gastroenterology & hepatology (2014), 11 (8), 506-14 ISSN:.An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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457Dahiya, D.; Nigam, P. S. Clinical Potential of Microbial Strains, Used in Fermentation for Probiotic Food, Beverages and in Synbiotic Supplements, as Psychobiotics for Cognitive Treatment through Gut-Brain Signaling. Microorganisms 2022, 10, 1687, DOI: 10.3390/microorganisms10091687Google ScholarThere is no corresponding record for this reference.
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458Zawistowska-Rojek, A.; Tyski, S. How to Improve Health with Biological Agents-Narrative Review. Nutrients 2022, 14, 1700, DOI: 10.3390/nu14091700Google Scholar458https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xhtlenu7zI&md5=ef05cd49a7506e5a1b3bc5bbc3225625How to Improve Health with Biological Agents-Narrative ReviewZawistowska-Rojek, Anna; Tyski, StefanNutrients (2022), 14 (9), 1700CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. The proper functioning of the human organism is dependent on a no. of factors. The health condition of the organism can be often enhanced through appropriate supplementation, as well as the application of certain biol. agents. Probiotics, i.e., live microorganisms that exert a beneficial effect on the health of the host when administered in adequate amts., are often used in commonly available dietary supplements or functional foods, such as yoghurts. Specific strains of microorganisms, administered in appropriate amts., may find application in the treatment of conditions such as various types of diarrhoea (viral, antibiotic-related, caused by Clostridioides difficile), irritable bowel syndrome, ulcerative colitis, Crohns disease, or allergic disorders. In contrast, live microorganisms capable of exerting influence on the nervous system and mental health through interactions with the gut microbiome are referred to as psychobiotics. Live microbes are often used in combination with prebiotics to form synbiotics, which stimulate growth and/or activate the metab. of the healthy gut microbiome. Prebiotics may serve as a substrate for the growth of probiotic strains or fermn. processes. Compared to prebiotic substances, probiotic microorganisms are more tolerant of environmental conditions, such as oxygenation, pH, or temp. in a given organism. It is also worth emphasizing that the health of the host may be influenced not only by live microorganisms, but also by their metabolites or cell components, which are referred to as postbiotics and paraprobiotics. This work presents the mechanisms of action employed by probiotics, prebiotics, synbiotics, postbiotics, paraprobiotics, and psychobiotics, together with the results of studies confirming their effectiveness and impact on consumer health.
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459Gibson, G. R.; Hutkins, R.; Sanders, M. E.; Prescott, S. L.; Reimer, R. A.; Salminen, S. J.; Scott, K.; Stanton, C.; Swanson, K. S.; Cani, P. D. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology 2017, 14, 491– 502, DOI: 10.1038/nrgastro.2017.75Google Scholar459https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cnotVSjtw%253D%253D&md5=2290a998bde9275fdaa2be7aa7ddad72Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebioticsGibson Glenn R; Hutkins Robert; Sanders Mary Ellen; Prescott Susan L; Reimer Raylene A; Salminen Seppo J; Scott Karen; Stanton Catherine; Swanson Kelly S; Cani Patrice D; Verbeke Kristin; Reid GregorNature reviews. Gastroenterology & hepatology (2017), 14 (8), 491-502 ISSN:.In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.
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460Swanson, K. S.; Gibson, G. R.; Hutkins, R.; Reimer, R. A.; Reid, G.; Verbeke, K.; Scott, K. P.; Holscher, H. D.; Azad, M. B.; Delzenne, N. M. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nature Reviews Gastroenterology & Hepatology 2020, 17, 687– 701, DOI: 10.1038/s41575-020-0344-2Google Scholar460https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38fosF2gsg%253D%253D&md5=d44b595e57356e2fc8ccfa771dce6b34The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbioticsSwanson Kelly S; Gibson Glenn R; Hutkins Robert; Reimer Raylene A; Reid Gregor; Verbeke Kristin; Verbeke Kristin; Scott Karen P; Holscher Hannah D; Azad Meghan B; Delzenne Nathalie M; Sanders Mary EllenNature reviews. Gastroenterology & hepatology (2020), 17 (11), 687-701 ISSN:.In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host". The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.
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461Salminen, S.; Collado, M. C.; Endo, A.; Hill, C.; Lebeer, S.; Quigley, E. M. M.; Sanders, M. E.; Shamir, R.; Swann, J. R.; Szajewska, H. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology 2021, 18, 649– 667, DOI: 10.1038/s41575-021-00440-6Google Scholar461https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c%252FgtlWlsA%253D%253D&md5=76d676b987bba5600ef08a2268b98b73The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbioticsSalminen Seppo; Collado Maria Carmen; Endo Akihito; Hill Colin; Hill Colin; Lebeer Sarah; Quigley Eamonn M M; Sanders Mary Ellen; Shamir Raanan; Shamir Raanan; Swann Jonathan R; Swann Jonathan R; Szajewska Hania; Vinderola GabrielNature reviews. Gastroenterology & hepatology (2021), 18 (9), 649-667 ISSN:.In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term 'postbiotics' is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products.
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462Sarkar, A.; Lehto, S. M.; Harty, S.; Dinan, T. G.; Cryan, J. F.; Burnet, P. W. J. Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals. Trends Neurosci. 2016, 39, 763– 781, DOI: 10.1016/j.tins.2016.09.002Google Scholar462https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhslels7fI&md5=2b8196a74542b35e478de6c67784cf93Psychobiotics and the Manipulation of Bacteria-Gut-Brain SignalsSarkar, Amar; Lehto, Soili M.; Harty, Siobhan; Dinan, Timothy G.; Cryan, John F.; Burnet, Philip W. J.Trends in Neurosciences (2016), 39 (11), 763-781CODEN: TNSCDR; ISSN:0166-2236. (Elsevier Ltd.)Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut-brain signalling mechanisms enabling psychobiotic effects, such as metabolite prodn. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.
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463Long-Smith, C.; O’Riordan, K. J.; Clarke, G.; Stanton, C.; Dinan, T. G.; Cryan, J. F. Microbiota-Gut-Brain Axis: New Therapeutic Opportunities. Annu. Rev. Pharmacol Toxicol 2020, 60, 477– 502, DOI: 10.1146/annurev-pharmtox-010919-023628Google Scholar463https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslCgu7nJ&md5=65468af6e88f3e9beda5f7da23a715edMicrobiota-Gut-Brain Axis: New Therapeutic OpportunitiesLong-Smith, Caitriona; O'Riordan, Kenneth J.; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.Annual Review of Pharmacology and Toxicology (2020), 60 (), 477-502CODEN: ARPTDI; ISSN:0362-1642. (Annual Reviews)The traditional fields of pharmacol. and toxicol. are beginning to consider the substantial impact our gut microbiota has on host physiol. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addn. to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochem. signaling, direct enteric nervous system routes and the vagus nerve, and the prodn. of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurol. disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clin. management of brain disorders.
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464Pferschy-Wenzig, E. M.; Pausan, M. R.; Ardjomand-Woelkart, K.; Röck, S.; Ammar, R. M.; Kelber, O.; Moissl-Eichinger, C.; Bauer, R. Medicinal Plants and Their Impact on the Gut Microbiome in Mental Health: A Systematic Review. Nutrients 2022, 14, 2111, DOI: 10.3390/nu14102111Google Scholar464https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsVCqsr7F&md5=16c71833085699501bb0bea9aa7e0573Medicinal Plants and Their Impact on the Gut Microbiome in Mental Health: A Systematic ReviewPferschy-Wenzig, Eva-Maria; Pausan, Manuela R.; Ardjomand-Woelkart, Karin; Roeck, Stefanie; Ammar, Ramy M.; Kelber, Olaf; Moissl-Eichinger, Christine; Bauer, RudolfNutrients (2022), 14 (10), 2111CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Various neurocognitive and mental health-related conditions have been assocd. with the gut microbiome, implicating a microbiome-gut-brain axis (MGBA). The aim of this systematic review was to identify, categorize, and review clin. evidence supporting medicinal plants for the treatment of mental disorders and studies on their interactions with the gut microbiota. This review included medicinal plants for which clin. studies on depression, sleeping disorders, anxiety, or cognitive dysfunction as well as scientific evidence of interaction with the gut microbiome were available. The studies were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Eighty-five studies met the inclusion criteria and covered thirty mental health-related medicinal plants with data on interaction with the gut microbiome. Only a few studies have been specifically designed to assess how herbal prepns. affect MGBA-related targets or pathways. However, many studies provide hints of a possible interaction with the MGBA, such as an increased abundance of health-beneficial microorganisms, anti-inflammatory effects, or MGBA-related pathway effects by gut microbial metabolites. Data for Panax ginseng, Schisandra chinensis, and Salvia rosmarinus indicate that the interaction of their constituents with the gut microbiota could mediate mental health benefits. Studies specifically assessing the effects on MGBA-related pathways are still required for most medicinal plants.
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465PitchBook. https://www.pitchbook.com/ (accessed March 30, 2023).Google ScholarThere is no corresponding record for this reference.
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466Black, C. J.; Ford, A. C. Global burden of irritable bowel syndrome: trends, predictions and risk factors. Nature Reviews Gastroenterology & Hepatology 2020, 17, 473– 486, DOI: 10.1038/s41575-020-0286-8Google Scholar466https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zlvVSnsQ%253D%253D&md5=f3bdedacf74908abb87ab505df660d03Global burden of irritable bowel syndrome: trends, predictions and risk factorsBlack Christopher J; Ford Alexander C; Black Christopher J; Ford Alexander CNature reviews. Gastroenterology & hepatology (2020), 17 (8), 473-486 ISSN:.Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction worldwide, defined according to patterns of gastrointestinal symptoms as described by the Rome diagnostic criteria. However, these criteria, developed with reference to research conducted largely in Western populations, might be limited in their applicability to other countries and cultures. Epidemiological data show a wide variation in the prevalence of IBS globally and more rigorous studies are needed to accurately determine any differences that might exist between countries as well as the potential explanations. The effects of IBS on the individual, in terms of their quality of life, and on health-care delivery and society, in terms of economic costs, are considerable. Although the magnitude of these effects seems to be comparable between nations, their precise nature can vary based on the existence of societal and cultural differences. The pathophysiology of IBS is complex and incompletely understood; genetics, diet and the gut microbiome are all recognized risk factors, but the part they play might be influenced by geography and culture, and hence their relative importance might vary between countries. This Review aims to provide an overview of the burden of IBS in a global context, to discuss future implications for the care of people with IBS worldwide, and to identify key areas for further research.
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467Fecal Microbiota Transplantation. https://www.idsociety.org/public-health/emerging-clinical-issues/emerging-clinical-issues/fecal-microbiota-transplantation/ (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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468BiomeBank announces world first regulatory approval for donor derived microbiome drug. https://www.biomebank.com/news/media-release/biomebank-announces-world-first-regulatory-approval-for-donor-derived-microbiome-drug/ (accessed November 22, 2022).Google ScholarThere is no corresponding record for this reference.
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469Ferring Receives U.S. FDA Approval for REBYOTA (fecal microbiota, live-jslm) – A Novel First-in-Class Microbiota-Based Live Biotherapeutic. https://ferringusa.com/?press=ferring-receives-u-s-fda-approval-for-rebyota-fecal-microbiota-live-jslm-a-novel-first-in-class-microbiota-based-live-biotherapeutic (accessed December 6, 2022).Google ScholarThere is no corresponding record for this reference.
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470Clinical Trials. https://www.clinicaltrials.gov/ (accessed January 27, 2023).Google ScholarThere is no corresponding record for this reference.
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471Fijan, S. Microorganisms with claimed probiotic properties: an overview of recent literature. Int. J. Environ. Res. Public Health 2014, 11, 4745– 4767, DOI: 10.3390/ijerph110504745Google Scholar471https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cjmt1CjsQ%253D%253D&md5=665bec4cd83ddfc93d8208a5f212d019Microorganisms with claimed probiotic properties: an overview of recent literatureFijan SabinaInternational journal of environmental research and public health (2014), 11 (5), 4745-67 ISSN:.Probiotics are defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Health benefits have mainly been demonstrated for specific probiotic strains of the following genera: Lactobacillus, Bifidobacterium, Saccharomyces, Enterococcus, Streptococcus, Pediococcus, Leuconostoc, Bacillus, Escherichia coli. The human microbiota is getting a lot of attention today and research has already demonstrated that alteration of this microbiota may have far-reaching consequences. One of the possible routes for correcting dysbiosis is by consuming probiotics. The credibility of specific health claims of probiotics and their safety must be established through science-based clinical studies. This overview summarizes the most commonly used probiotic microorganisms and their demonstrated health claims. As probiotic properties have been shown to be strain specific, accurate identification of particular strains is also very important. On the other hand, it is also demonstrated that the use of various probiotics for immunocompromised patients or patients with a leaky gut has also yielded infections, sepsis, fungemia, bacteraemia. Although the vast majority of probiotics that are used today are generally regarded as safe and beneficial for healthy individuals, caution in selecting and monitoring of probiotics for patients is needed and complete consideration of risk-benefit ratio before prescribing is recommended.
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472Effect of Two Probiotic Formulations on Mental Health and Mood Biomarkers in Adults With Depressive Symptoms. https://clinicaltrials.gov/ct2/show/NCT05564767?term=NCT05564767&draw=2&rank=1 (accessed November 27, 2022).Google ScholarThere is no corresponding record for this reference.
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473Effects of Probiotics on Gut Microbiota, Endocannabinoid and Immune Activation and Symptoms of Fatigue in Dancers. https://clinicaltrials.gov/ct2/show/NCT05567653?term=NCT05567653&draw=2&rank=1 (accessed November 27, 2022).Google ScholarThere is no corresponding record for this reference.
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474Probiotics on Sleep Among Adults Study. https://clinicaltrials.gov/ct2/show/NCT04767997?term=NCT04767997&draw=2&rank=1 (accessed November 27, 2022).Google ScholarThere is no corresponding record for this reference.
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475Rode, J.; Edebol Carlman, H. M. T.; König, J.; Repsilber, D.; Hutchinson, A. N.; Thunberg, P.; Andersson, P.; Persson, J.; Kiselev, A.; Lathrop Stern, L. Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial. Front Nutr 2022, 9, 827182, DOI: 10.3389/fnut.2022.827182Google Scholar475https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2Mnit1Oktg%253D%253D&md5=992d10e4fde63393ce50a0df69755f33Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical TrialRode Julia; Edebol Carlman Hanna M T; Konig Julia; Repsilber Dirk; Hutchinson Ashley N; Salomon Benita; Brummer Robert J; Thunberg Per; Mohammed Ahmed Abdulilah; Andersson Pernilla; Persson Jonas; Kiselev Andrey; Lathrop Stern Lori; Labus Jennifer SFrontiers in nutrition (2022), 9 (), 827182 ISSN:2296-861X.Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited. Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 10(9) CFU/day) affected functional brain responses in healthy subjects during an emotional attention task. Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed. Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention. Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest. Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].
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476Patterson, E.; Griffin, S. M.; Ibarra, A.; Ellsiepen, E.; Hellhammer, J. Lacticaseibacillus paracasei Lpc-37® improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study). Neurobiol Stress 2020, 13, 100277, DOI: 10.1016/j.ynstr.2020.100277Google Scholar476https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitVWgsLvF&md5=88dbb2663f829cffce4519fe835e874eLacticaseibacillus paracasei Lpc-37 improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study)Patterson, Elaine; Griffin, Sile M.; Ibarra, Alvin; Ellsiepen, Emilia; Hellhammer, JulianeNeurobiology of Stress (2020), 13 (), 100277CODEN: NSETCA; ISSN:2352-2895. (Elsevier Inc.)Chronic stress is a risk-factor for the development of mood and stress-related disorders. Clin. evidence indicates that probiotics can influence the stress response and mood. The Sisu study investigated whether Lacticaseibacillus paracasei Lpc-37 (Lpc-37) could modulate stress, mood and well-being. Prior to a two-week run-in period, 120 healthy adults (18-45 y) were stratified for sex and chronic stress and randomized to either 1.75 x 1010 colony forming units (CFU) of Lpc-37 or placebo (1:1) per day for 5 wk. The primary objective was the effect of Lpc-37 on heart rate (HR) in response to the Trier Social Stress Test (TSST). Secondary objectives were assessed by biomarkers and self-report scales over the study. The primary hypothesis was not met in either the Intention-to-Treat (ITT) or Per Protocol (PP) population, but Lpc-37 reduced the increase in HR in participants with low chronic stress (LCS) and increased HR in participants with high chronic stress (HCS) during the TSST. Supporting significant efficacy in the PP population (n = 113), Lpc-37 reduced perceived stress following intervention. More significant effects were identified within the subgroups where Lpc-37 reduced exhaustion during the TSST and normalized cortisol levels at 8pm in participants with LCS, reduced perceived stress also in females, and increased perceived health and sleep-related recovery in participants with HCS. Adverse events (AEs) were similar between groups, there were no severe AEs, and vital signs remained unchanged. Overall, Lpc-37 reduced perceived stress compared to placebo. Other beneficial effects within biomarkers related to stress indicate that the effects of Lpc-37 may be differentially dependent on sex and chronic stress. (ClinicalTrials.gov: NCT03494725).
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477Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects. https://www.clinicaltrials.gov/ct2/show/NCT03494725?term=NCT03494725&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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478The Cognitive Effects of 6 Weeks Administration With a Probiotic. https://www.clinicaltrials.gov/ct2/show/NCT03601559?term=NCT03601559&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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479Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects. https://www.clinicaltrials.gov/ct2/show/NCT03615651?term=NCT03615651&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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480Lactobacillus Plantarum DR7 for Gut-Brain-Axis Benefits (DR7). https://www.clinicaltrials.gov/ct2/show/NCT03370458?term=NCT03370458&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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481Sur, D.; Manna, B.; Niyogi, S. K.; Ramamurthy, T.; Palit, A.; Nomoto, K.; Takahashi, T.; Shima, T.; Tsuji, H.; Kurakawa, T. Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized, double-blind placebo-controlled field trial in an urban slum. Epidemiology and Infection 2011, 139, 919– 926, DOI: 10.1017/S0950268810001780Google Scholar481https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MvmtlWktw%253D%253D&md5=18d9556544808794f0dc81193a23d533Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized, double-blind placebo-controlled field trial in an urban slumSur D; Manna B; Niyogi S K; Ramamurthy T; Palit A; Nomoto K; Takahashi T; Shima T; Tsuji H; Kurakawa T; Takeda Y; Nair G B; Bhattacharya S KEpidemiology and infection (2011), 139 (6), 919-26 ISSN:.Acute diarrhoea remains a major public health challenge in developing countries. We examined the role of a probiotic in the prevention of acute diarrhoea to discover if there was an effect directed towards a specific aetiology. A double-blind, randomized, controlled field trial involving 3758 children aged 1-5 years was conducted in an urban slum community in Kolkata, India. Participants were given either a probiotic drink containing Lactobacillus casei strain Shirota or a nutrient drink daily for 12 weeks. They were followed up for another 12 weeks. The primary outcome of this study was the occurrence of first episodes of diarrhoea. We assessed this during 12 weeks of intake of study agent and also for 12 weeks of follow-up. There were 608 subjects with diarrhoea in the probiotic group and 674 subjects in the nutrient group during the study period of 24 weeks. The level of protective efficacy for the probiotic was 14% (95% confidence interval 4-23, P<0·01 in adjusted model). The reduced occurrence of acute diarrhoea in the probiotic group compared to nutrient group was not associated with any specific aetiology. No adverse event was observed in children of either probiotic or nutrient groups. The study suggests that daily intake of a probiotic drink can play a role in prevention of acute diarrhoea in young children in a community setting of a developing country.
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482Cottrell, J.; Koenig, K.; Perfekt, R.; Hofmann, R.; For the Loperamide–Simethicone Acute Diarrhoea Study, T. Comparison of Two Forms of Loperamide–Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial. Drugs R&D 2015, 15, 363– 373, DOI: 10.1007/s40268-015-0111-yGoogle ScholarThere is no corresponding record for this reference.
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483Skrzydło-Radomańska, B.; Prozorow-Król, B.; Cichoż-Lach, H.; Majsiak, E.; Bierła, J. B.; Kanarek, E.; Sowińska, A.; Cukrowska, B. The Effectiveness and Safety of Multi-Strain Probiotic Preparation in Patients with Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Controlled Study. Nutrients 2021, 13, 756, DOI: 10.3390/nu13030756Google Scholar483https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtFGisrrO&md5=daf5ccef30be66efaa9941a085951d88The effectiveness and safety of multi-strain probiotic preparation in patients with diarrhea-predominant irritable bowel syndrome: a randomized controlled studySkrzydlo-Radomanska, Barbara; Prozorow-Krol, Beata; Cichoz-Lach, Halina; Majsiak, Emilia; Bierla, Joanna Beata; Kanarek, Ewelina; Sowinska, Agnieszka; Cukrowska, BozenaNutrients (2021), 13 (3), 756CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)The aim of this randomized double-blind placebo-controlled study was to evaluate the effectiveness and safety of multi-strain probiotic in adults with diarrhea-predominant irritable bowel syndrome (IBS-D). The patients were randomized to receive a mixt. of Lactobacillus, Bifidobacterium, and Streptococcus thermophilus strains or placebo for eight weeks. Primary endpoints included changes in symptom severity and improvement assessed with the IBS Severity Scoring System (IBS-SSS) and Global Improvement Scale (IBS-GIS). The probiotic in comparison with placebo significantly improved the IBS symptom severity (the change of total IBS-SSS score from baseline -165.8 ± 78.9 in the probiotic group and -105.6 ± 60.2 in the placebo group, p = 0.005) and in the specific scores related to the severity of pain (p = 0.015) and the quality of life (p = 0.016) after eight weeks of intervention. The probiotic group indicated an improvement in symptoms with the use of the IBS-GIS compared with the placebo group after four (p = 0.04) and eight weeks (p = 0.003). The occurrence of adverse events did not differ between study groups. In conclusion, the multi-strain probiotic intervention resulted in a significant improvement in IBS symptoms evaluated with the use of both IBS-SSS and IBS-GIS scales. The results suggest that the studied probiotic prepn. is well tolerated and safe and can offer benefits for patients with IBS-D. (registration no. in Clinicaltrials.gov NCT 04662957).
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484Quigley, E. M. M.; Markinson, L.; Stevenson, A.; Treasure, F. P.; Lacy, B. E. Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome. Aliment. Pharmacol. Ther. 2023, 57, 81– 93, DOI: 10.1111/apt.17310Google Scholar484https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFalsLfF&md5=9d42fc333ad4607a2a0d0a361274ae6fRandomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndromeQuigley, Eamonn M. M.; Markinson, Louise; Stevenson, Alex; Treasure, F. Peter; Lacy, Brian E.Alimentary Pharmacology and Therapeutics (2023), 57 (1), 81-93CODEN: APTHEN; ISSN:0269-2813. (Wiley-Blackwell)MRx1234 is a live biotherapeutic product that contains a strain of Blautia hydrogenotrophica. It is in development for the treatment of irritable bowel syndrome (IBS). To assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS-C) or diarrhoea (IBS-D) Methods : We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients aged 18-70 years in two parallel cohorts (IBS-C; IBS-D) were randomised (1:1) to MRx1234 or placebo for 8 wk. The primary efficacy endpoint was overall responder rate-a composite of improved bowel habit (IBS-C: stool frequency; IBS-D: stool consistency) and abdominal pain intensity-for ≥50% of the treatment period in each cohort. Statistical testing was at a one-sided 0.10 significance level. Of 366 randomised patients (164 IBS-C; 202 IBS-D), 365 received any study medication (177 MRx1234, 188 placebo). Numerically, although not statistically significantly different, more patients who received MRx1234 than placebo were overall responders in the IBS-C (25.0% vs. 17.1%) and IBS-D (23.4% vs. 17.8%) cohorts. Similar results were obsd. in the addnl. combined cohort anal. (24.1% vs. 17.5%; p = 0.063). For the components of the primary endpoint, significantly more patients on MRx1234 than placebo reported improvement in bowel habit in the IBS-C, IBS-D and combined cohorts, while improvements in abdominal pain were obsd. in each cohort. The safety profile of MRx1234 was similar to placebo. MRx1234 has the potential to become a novel, safe treatment option for patients with IBS-C or IBS-D, and for those who have mixed symptoms or transition between subtypes. #NCT03721107.
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485Effect of Lactobacillus Gasseri DSM 27123 on Functional Constipation in Healthy Women. https://www.clinicaltrials.gov/ct2/show/NCT02592200?term=NCT02592200&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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486Dietary Supplementation Effects on Bowel Movement Frequency and Intestinal Biological Markers in Seniors Presenting Slowed Intestinal Transit. https://www.clinicaltrials.gov/ct2/show/NCT04304170?term=NCT04304170&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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487Multi Strain Probiotic Preparation in Patients With Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT04662957?term=NCT04662957&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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488The Effect of Probiotic Supported Yogurt Consumption on Gastrointestinal Symptoms. https://www.clinicaltrials.gov/ct2/show/NCT05566171?term=NCT05566171&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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489B. Lactis HN019 for Functional Constipation (CTT). https://www.clinicaltrials.gov/ct2/show/NCT01463293?term=NCT01463293&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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490Effects of Cultura Yoghurt in Relation to Transit Time and Digestive Discomfort in Healthy Women and Men. https://www.clinicaltrials.gov/ct2/show/NCT01102036?term=NCT01102036&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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491A Trial for New Treatment of Adult Participants With Irritable Bowel Syndrome. https://clinicaltrials.gov/ct2/show/NCT03721107?term=NCT03721107&draw=2&rank=1 (accessed Feb 16, 2023).Google ScholarThere is no corresponding record for this reference.
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492Randomized Controlled Field Trial of a Probiotics to Assess Its Role in Preventig Diarrhoea (Yakult). https://www.clinicaltrials.gov/ct2/show/NCT00534170?term=NCT00534170&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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493Probiotics and Hospital Outcome in the Elderly (PROAGE). https://www.clinicaltrials.gov/ct2/show/NCT00794924?term=NCT00794924&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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494Evaluation of the Efficacy of Two Probiotic Strains for Irritable Bowel Syndrome (14PIHL). https://www.clinicaltrials.gov/ct2/show/NCT02213172?term=NCT02213172&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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495A Comparison of Three Medications to Treat Diarrhea in Adults. https://www.clinicaltrials.gov/ct2/show/NCT00807326?term=NCT00807326&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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496A Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT05054309?term=NCT05054309&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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497Study to Evaluate a Probiotic in Healthy Subjects With a History of Abdominal Discomfort and Bloating. https://www.clinicaltrials.gov/ct2/show/NCT01099696?term=NCT01099696&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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498Efficacy of a Multi-strain Probiotic in the Treatment of Irritable Bowel Syndrome (IBS). https://www.clinicaltrials.gov/ct2/show/NCT01887834?term=NCT01887834&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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499Trial to Evaluate Dietary Supplements to Maintain Gut Health During Travel (P3). https://www.clinicaltrials.gov/ct2/show/NCT04605783?term=NCT04605783&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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500To Study the Efficacy and Safety of L. Plantarum UALp-05TM in Diarrhea- Predominant-irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT04950296?term=NCT04950296&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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501Saccharomyces Cerevisiae for Irritable Bowel Syndrome (IBS). https://www.clinicaltrials.gov/ct2/show/NCT05149599?term=NCT05149599&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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502Johnstone, N.; Milesi, C.; Burn, O.; van den Bogert, B.; Nauta, A.; Hart, K.; Sowden, P.; Burnet, P. W. J.; Cohen Kadosh, K. Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18–25 years) with corresponding changes in gut bacterial composition. Sci. Rep. 2021, 11, 8302, DOI: 10.1038/s41598-021-87865-wGoogle Scholar502https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXpt1Wkurk%253D&md5=46c02b64c8e170d6225768d3f2d3ef4eAnxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18-25 years) with corresponding changes in gut bacterial compositionJohnstone, Nicola; Milesi, Chiara; Burn, Olivia; van den Bogert, Bartholomeus; Nauta, Arjen; Hart, Kathryn; Sowden, Paul; Burnet, Philip W. J.; Cohen Kadosh, KathrinScientific Reports (2021), 11 (1), 8302CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Current research implicates pre- and probiotic supplementation as a potential tool for improving symptomol. in phys. and mental ailments, which makes it an attractive concept for clinicians and consumers alike. Here we focus on the transitional period of late adolescence and early adulthood during which effective interventions, such as nutritional supplementation to influence the gut microbiota, have the potential to offset health-related costs in later life. We examd. multiple indexes of mood and well-being in 64 healthy females in a 4-wk double blind, placebo controlled galacto-oligosaccharides (GOS) prebiotic supplement intervention and obtained stool samples at baseline and follow-up for gut microbiota sequencing and analyses. We report effects of the GOS intervention on self-reported high trait anxiety, attentional bias, and bacterial abundance, suggesting that dietary supplementation with a GOS prebiotic may improve indexes of pre-clin. anxiety. Gut microbiota research has captured the imagination of the scientific and lay community alike, yet we are now at a stage where this early enthusiasm will need to be met with rigorous research in humans. Our work makes an important contribution to this effort by combining a psychobiotic intervention in a human sample with comprehensive behavioral and gut microbiota measures.
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503Parilli-Moser, I.; Domínguez-López, I.; Trius-Soler, M.; Castellví, M.; Bosch, B.; Castro-Barquero, S.; Estruch, R.; Hurtado-Barroso, S.; Lamuela-Raventós, R. M. Consumption of peanut products improves memory and stress response in healthy adults from the ARISTOTLE study: A 6-month randomized controlled trial. Clin. Nutr. 2021, 40, 5556– 5567, DOI: 10.1016/j.clnu.2021.09.020Google Scholar503https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlantbjF&md5=2adc0ba0d3a56ab9ccd080ea8288c72eConsumption of peanut products improves memory and stress response in healthy adults from the ARISTOTLE study: A 6-month randomized controlled trialParilli-Moser, Isabella; Dominguez-Lopez, Ines; Trius-Soler, Marta; Castellvi, Magda; Bosch, Beatriz; Castro-Barquero, Sara; Estruch, Ramon; Hurtado-Barroso, Sara; Lamuela-Raventos, Rosa M.Clinical Nutrition (2021), 40 (11), 5556-5567CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)Peanuts are rich in bioactive compds. that may have a pos. impact on memory and stress response.To evaluate the effect of regular consumption of peanut products on cognitive functions and stress response in healthy young adults.A three-arm parallel-group randomized controlled trial was conducted in 63 healthy young adults that consumed 25 g/day of skin roasted peanuts (SRP, n = 21), 32 g/d of peanut butter (PB, n = 23) or 32 g/d of a control butter made from peanut oil (free of phenolic compds. and fiber) (CB, n = 19) for six months. Polyphenol intake, cognitive functions, and anxiety and depression scores were evaluated using validated tests. Fecal short-chain fatty acids (SCFAs) and plasma and fecal fatty acids were assessed by chromatog. methods. Urinary cortisol was quantified by an enzymic method.Comparing the two interventions with the control, a significant redn. in anxiety scores was obsd. in the SRP compared to the CB group. After the intervention, consumers of SRP and PB had an improved immediate memory (p = 0.046 and p = 0.011). Lower anxiety scores were assocd. with SRP and PB (p < 0.001 and p = 0.002, resp.) and lower depression scores with SRP, PB and CB (p = 0.007, p = 0.003 and p = 0.032, resp.). Memory functions and stress response were significantly correlated with polyphenol intake, fecal SCFAs, plasma and fecal very long chain satd. fatty acids (VLCSFAs).Regular peanut and peanut butter consumption may enhance memory function and stress response in a healthy young population. These effects seem to be assocd. with the intake of peanut polyphenols, increased levels of fecal SCFAs, and unexpectedly, VLCSFAs, which were also present in the control product.
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504Prebiotics and Stress Reduction in Women. https://www.clinicaltrials.gov/ct2/show/NCT05372601?term=NCT05372601&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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505Evaluating the Effects of Prebiotics on Sleep, the Gut Microbiome, Cognition, Immune Function and Stress. https://www.clinicaltrials.gov/ct2/show/NCT05239845?term=NCT05239845&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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506Healthy Prebiotic and Postbiotic Effects of Peanuts and Peanut Butter: College Intervention Trial (ARISTOTLE). https://www.clinicaltrials.gov/ct2/show/NCT04324749?term=NCT04324749&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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507Polyphenols, Prebiotics, the Gut Microbiome and Stress. https://www.clinicaltrials.gov/ct2/show/NCT05528575?term=NCT05528575&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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508Prebiotics and Mental Health: Behavioural. https://www.clinicaltrials.gov/ct2/show/NCT04616937?term=NCT04616937&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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509Selling, J.; Swann, P.; Madsen, L. R., 2nd; Oswald, J. Improvement in Gastroesophageal Reflux Symptoms From a Food-grade Maltosyl-isomaltooligosaccharide Soluble Fiber Supplement: A Case Series. Integr. Med. 2018, 17, 40– 42Google Scholar509https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7htlShtw%253D%253D&md5=8cc979543313d4e4486c5c9d55ceb387Improvement in Gastroesophageal Reflux Symptoms From a Food-grade Maltosyl-isomaltooligosaccharide Soluble Fiber Supplement: A Case SeriesSelling John; Swann Peter; Madsen Lee R 2nd; Oswald JackIntegrative medicine (Encinitas, Calif.) (2018), 17 (5), 40-42 ISSN:1546-993X.Gastroesophageal reflux disease (GERD) is a very common medical condition. Symptom improvement from ingested prebiotic soluble fiber has not been reported previously. In fact, a related soluble fiber, fructooligosaccharides, has been shown to worsen GERD. We report on a series of 24 patients with GERD, 88% of which improved after several weeks of daily consumption of a specific maltosyl-isomaltooligosaccharide (MIMO) fermented prebiotic soluble fiber. We also report on 2 proton pump inhibitor (PPI)-dependent patients with GERD who, after beginning daily MIMO, were able to eliminate PPI therapy. The hypotheses explaining the mechanism for GERD improvement with MIMO is discussed. To the best of our knowledge, these cases are the first time any prebiotic soluble fiber has been reported to improve or eliminate symptoms of GERD and enable patients with GERD to decrease or eliminate their PPI therapy.
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510Ansell, J.; Butts, C. A.; Paturi, G.; Eady, S. L.; Wallace, A. J.; Hedderley, D.; Gearry, R. B. Kiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled study. Nutr. Res. (N.Y.) 2015, 35, 401– 408, DOI: 10.1016/j.nutres.2015.04.005Google Scholar510https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnt1ersb4%253D&md5=a18d0435a7b48f860f0215c05b43775aKiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled studyAnsell, Juliet; Butts, Christine A.; Paturi, Gunaranjan; Eady, Sarah L.; Wallace, Alison J.; Hedderley, Duncan; Gearry, Richard B.Nutrition Research (New York, NY, United States) (2015), 35 (5), 401-408CODEN: NTRSDC; ISSN:0271-5317. (Elsevier)The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, double-blind, placebo-controlled study, we examd. the effects of Actazin and Gold, kiwifruit-derived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14-day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were obsd. in stool form as detd. by use of the Bristol stool scale. In a subgroup anal. of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the no. of daily bowel movements by greater than 1 bowel movement per wk. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup anal. of responders. This study demonstrated that Actazin and Gold produced clin. meaningful increases in bowel movements in healthy individuals.
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511Blatchford, P.; Stoklosinski, H.; Eady, S.; Wallace, A.; Butts, C.; Gearry, R.; Gibson, G.; Ansell, J. Consumption of kiwifruit capsules increases Faecalibacterium prausnitzii abundance in functionally constipated individuals: a randomised controlled human trial. J. Nutr Sci. 2017, 6, e52, DOI: 10.1017/jns.2017.52Google Scholar511https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXls12gu7g%253D&md5=dc4a812ca413cc495e808a9e192fe605Consumption of kiwifruit capsules increases Faecalibacterium prausnitziiabundance in functionally constipated individuals: a randomised controlledhuman trialBlatchford, Paul; Stoklosinski, Halina; Eady, Sarah; Wallace, Alison; Butts, Christine; Gearry, Richard; Gibson, Glenn; Ansell, JulietJournal of Nutritional Science (2017), 6 (), e52/1-e52/10CODEN: JNSOAI; ISSN:2048-6790. (Cambridge University Press)This study investigated the impact of ACTAZINTM green (2400 and 600 mg) and LivauxTM (2400 mg) gold kiwifruit supplements on faecal microbial compn. and metabolites in healthy and functionally constipated (FC) participants. The participants were recruited into the healthy group (n 20; one of whom did not complete the study) and the FC group (n 9), each of whom consumed all the treatments and a placebo (isomalt) for 4 wk in a randomised cross-over design interspersed with 2-wk washout periods. Modiflcation of faecal microbiota compn. and metab. was detd. by 16S rRNA gene sequencing and GC, and colonic pH was calcd. using SmartPill wireless motility capsules. A total of thirty-two taxa were measured at greater than 1% abundance in at least one sample, ten of which differed signiflcantly between the baseline healthy and FC groups. Speciflcally, Bacteroidales and Roseburia spp. were signiflcantly more abundant (P < 0.05) in the healthy group and taxa including Ruminococcaceae, Dorea spp. and Akkermansia spp. were signiflcantly more abundant (P < 0.05) in the FC group. In the FC group, Faecalibacterium prausnitzii abundance signiflcantly increased (P = 0.024) from 3.4 to 7.0% following LivauxTM supplementation, with eight of the nine participants showing a net increase. Lower proportions of F. prausnitzii are often assocd. with gastrointestinal disorders. The discovery that LivauxTM supplementation increased F. prausnitzii abundance offers a potential strategy for improving gut microbiota compn., as F. prausnitzii is a butyrate producer and has also been shown to exert anti-inflammatory effects in many studies.
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512SILK, D. B. A.; DAVIS, A.; VULEVIC, J.; TZORTZIS, G.; GIBSON, G. R. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment. Pharmacol. Ther. 2009, 29, 508– 518, DOI: 10.1111/j.1365-2036.2008.03911.xGoogle Scholar512https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjslaltbg%253D&md5=09dbece5e9a12382749ee12439f7ace8Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndromeSilk, D. B. A.; Davis, A.; Vulevic, J.; Tzortzis, G.; Gibson, G. R.Alimentary Pharmacology and Therapeutics (2009), 29 (5), 508-518CODEN: APTHEN; ISSN:0269-2813. (Wiley-Blackwell)Background: Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). Aim: To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. Methods: In all, 44 patients with Rome II pos. IBS completed a 12-wk single center parallel crossover controlled clin. trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. Results: The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clin. parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). Conclusion: The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.
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513Tolerability Study of a Novel Microbiome Therapeutic in Subjects With Gastroesophageal Reflux Disease. https://www.clinicaltrials.gov/ct2/show/NCT04491734?term=NCT04491734&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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514Utility of the Administration of Chesnut and Quebracho Extract for Irritable Bowel Syndrome Diarrhea Predominant. https://www.clinicaltrials.gov/ct2/show/NCT05207618?term=NCT05207618&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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515Evaluation of the Efficacy of a New Specific Infant Formula in Case of Functional Constipation. https://www.clinicaltrials.gov/ct2/show/NCT05340712?term=NCT05340712&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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516ReFerm. https://referm.dk/ (accessed November 27, 2022).Google ScholarThere is no corresponding record for this reference.
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517Effect of Postbiotic Product on Colonic Barriers in IBS. https://www.clinicaltrials.gov/ct2/show/NCT05475314?term=NCT05475314&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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518Pilot Study to Assess the Effect of a Postbiotic Blend on Moderate Self-reported Anxiety (Anx). https://www.clinicaltrials.gov/ct2/show/NCT05562739?term=NCT05562739&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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519Evaluating the Safety and Efficacy of the Probiotic Bifidobacterium Longum ES1 and the Post Biotic Heat-treated Bifidobacterium Longum ES1 (HT-ES1) on IBS Symptom Severity in Patients With Diarrhoea Predominant Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT05339243?term=NCT05339243&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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520König, J.; Brummer, R. J. Faecal microbiota transplantation in IBS ─ new evidence for success?. Nature Reviews Gastroenterology & Hepatology 2020, 17, 199– 200, DOI: 10.1038/s41575-020-0282-zGoogle Scholar520https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB387ntVWqtg%253D%253D&md5=e30412f63f904df76eeec7def1975769Faecal microbiota transplantation in IBS - new evidence for success?Konig Julia; Brummer Robert JanNature reviews. Gastroenterology & hepatology (2020), 17 (4), 199-200 ISSN:.There is no expanded citation for this reference.
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521El-Salhy, M.; Winkel, R.; Casen, C.; Hausken, T.; Gilja, O. H.; Hatlebakk, J. G. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology 2022, 163, 982– 994.e14, DOI: 10.1053/j.gastro.2022.06.020Google Scholar521https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MjmtVejtA%253D%253D&md5=c454e89729d7379ea07f3be3ea52a0e0Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After TransplantationEl-Salhy Magdy; Winkel Renate; Casen Christina; Hausken Trygve; Gilja Odd Helge; Hatlebakk Jan GunnarGastroenterology (2022), 163 (4), 982-994.e14 ISSN:.BACKGROUND & AIMS: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS) are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects. METHODS: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed 5 questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index were analyzed using 16S ribosomal RNA gene polymerase chain reaction DNA amplification/probe hybridization covering the V3 to V9 regions. RESULTS: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The dysbiosis index decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded. CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events. This study was registered at www. CLINICALTRIALS: gov (NCT03822299).
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522Effects of Faecal Microbiota Transplantation in Patients With IBS. https://www.clinicaltrials.gov/ct2/show/NCT03822299?term=NCT03822299&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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524RCE With FMT in the Treatment of Childhood Constipation. https://www.clinicaltrials.gov/ct2/show/NCT05035784?term=NCT05035784&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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525FMT Capsules in Treatment of Patients With Insomnia Clinical Research. https://www.clinicaltrials.gov/ct2/show/NCT05427331?term=NCT05427331&draw=2&rank=1 (accessed November 28, 2022).Google ScholarThere is no corresponding record for this reference.
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526Haridy, R. Australia gives world-first regulatory approval to fecal transplant therapy. https://newatlas.com/medical/first-approval-fecal-transplant-gut-microbiome-therapy/ (accessed November 22, 2022).Google ScholarThere is no corresponding record for this reference.
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527Shepherd, T. A coup for poo: why the world’s first faecal transplant approval matters. The Guardian , November 12, 2022. https://www.theguardian.com/australia-news/2022/nov/13/a-coup-for-poo-why-the-worlds-first-faecal-transplant-approval-matters (accessed November 22, 2022).Google ScholarThere is no corresponding record for this reference.
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528FDA Approves First Fecal Microbiota Product. https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product (accessed December 2, 2022).Google ScholarThere is no corresponding record for this reference.
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529Shaffer, J. P.; Nothias, L.-F.; Thompson, L. R.; Sanders, J. G.; Salido, R. A.; Couvillion, S. P.; Brejnrod, A. D.; Lejzerowicz, F.; Haiminen, N.; Huang, S. Standardized multi-omics of Earth’s microbiomes reveals microbial and metabolite diversity. Nat. Microbiol. 2022, 7, 2128, DOI: 10.1038/s41564-022-01266-xGoogle Scholar529https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFOlsbrE&md5=6e1699fe35109ff8f4c0ad138a0fb2bfStandardized multi-omics of Earth's microbiomes reveals microbial and metabolite diversityShaffer, Justin P.; Nothias, Louis-Felix; Thompson, Luke R.; Sanders, Jon G.; Salido, Rodolfo A.; Couvillion, Sneha P.; Brejnrod, Asker D.; Lejzerowicz, Franck; Haiminen, Niina; Huang, Shi; Lutz, Holly L.; Zhu, Qiyun; Martino, Cameron; Morton, James T.; Karthikeyan, Smruthi; Nothias-Esposito, Melissa; Duhrkop, Kai; Bocker, Sebastian; Kim, Hyun Woo; Aksenov, Alexander A.; Bittremieux, Wout; Minich, Jeremiah J.; Marotz, Clarisse; Bryant, MacKenzie M.; Sanders, Karenina; Schwartz, Tara; Humphrey, Greg; Vasquez-Baeza, Yoshiki; Tripathi, Anupriya; Parida, Laxmi; Carrieri, Anna Paola; Beck, Kristen L.; Das, Promi; Gonzalez, Antonio; McDonald, Daniel; Ladau, Joshua; Karst, Soeren M.; Albertsen, Mads; Ackermann, Gail; DeReus, Jeff; Thomas, Torsten; Petras, Daniel; Shade, Ashley; Stegen, James; Song, Se Jin; Metz, Thomas O.; Swafford, Austin D.; Dorrestein, Pieter C.; Jansson, Janet K.; Gilbert, Jack A.; Knight, Rob; the Earth Microbiome Project 500 ConsortiumNature Microbiology (2022), 7 (12), 2128-2150CODEN: NMAICH; ISSN:2058-5276. (Nature Portfolio)Abstr.: Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics anal. of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liq. chromatog.-tandem mass spectrometry and gas chromatog. mass spectrometry). We used standardized protocols and anal. methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addn. to a ref. database for metagenomic and metabolomic data, we provide a framework for incorporating addnl. studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We addnl. show the power of certain chem., in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chem. ecol., and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment.
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530Zmora, N.; Zilberman-Schapira, G.; Suez, J.; Mor, U.; Dori-Bachash, M.; Bashiardes, S.; Kotler, E.; Zur, M.; Regev-Lehavi, D.; Brik, R. B.-Z. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell 2018, 174, 1388– 1405.e21, DOI: 10.1016/j.cell.2018.08.041Google Scholar530https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1Omu7bK&md5=908d0d3ebeb82249aea33d32ed64f363Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome FeaturesZmora, Niv; Zilberman-Schapira, Gili; Suez, Jotham; Mor, Uria; Dori-Bachash, Mally; Bashiardes, Stavros; Kotler, Eran; Zur, Maya; Regev-Lehavi, Dana; Brik, Rotem Ben-Zeev; Federici, Sara; Cohen, Yotam; Linevsky, Raquel; Rothschild, Daphna; Moor, Andreas E.; Ben-Moshe, Shani; Harmelin, Alon; Itzkovitz, Shalev; Maharshak, Nitsan; Shibolet, Oren; Shapiro, Hagit; Pevsner-Fischer, Meirav; Sharon, Itai; Halpern, Zamir; Segal, Eran; Elinav, EranCell (Cambridge, MA, United States) (2018), 174 (6), 1388-1405.e21CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-assocd. gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.
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531Zhu, G.; Zhao, J.; Zhang, H.; Chen, W.; Wang, G. Probiotics for mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Foods 2021, 10, 1672, DOI: 10.3390/foods10071672Google Scholar531https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXislCgu77M&md5=0ec20655d738b06303e4d76b36346b2bProbiotics for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-AnalysisZhu, Guangsu; Zhao, Jianxin; Zhang, Hao; Chen, Wei; Wang, GangFoods (2021), 10 (7), 1672CODEN: FOODBV; ISSN:2304-8158. (MDPI AG)Accumulating evidence from animal studies supports the potential role of probiotics and prebiotics in alleviating neurodegenerative diseases. However, whether dietary supplementation with probiotics improves cognitive function in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) is unclear. We searched literature databases for relevant randomized control trials and compared the outcomes between control/placebo and intervention groups. The results of the included studies were meta-analyzed using a random-effects model, with standardized mean differences (SMDs) and 95% confidence intervals (CIs) calcd. as summary statistics. We also performed a risk-of-bias assessment, sensitivity anal. and subgroup anal. Among the 294 articles identified, eight articles involving 174 patients with AD and 446 with MCI were included in the qual. synthesis and seven studies were meta-analyzed. Our anal. detected high between-group heterogeneity (SMD = 0.43, 95% CI -0.02-0.88, p < 0.0001, I2 = 86.4%) in cognitive function across the included studies. Subgroup analyses identified a significant effect of probiotics on cognitive function only in the studies involving people with MCI (I2 = 44%, p = 0.15 for heterogeneity, p = 0.0002 for overall effect). Our findings suggest that dietary supplementation with probiotics improves cognitive function, esp. in people with MCI.
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532Białecka-Dębek, A.; Granda, D.; Szmidt, M. K.; Zielińska, D. Gut microbiota, probiotic interventions, and cognitive function in the elderly: a review of current knowledge. Nutrients 2021, 13, 2514, DOI: 10.3390/nu13082514Google Scholar532https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVKgtrrL&md5=48c20a31877f490c3061c55c7c23fe11Gut Microbiota, Probiotic Interventions, and Cognitive Function in the Elderly: A Review of Current KnowledgeBialecka-Debek, Agata; Granda, Dominika; Szmidt, Maria Karolina; Zielinska, DorotaNutrients (2021), 13 (8), 2514CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Changes in the compn. and proportions of the gut microbiota may be assocd. with numerous diseases, including cognitive impairment. Over the recent years, the growing interest in this relation is obsd., but there are still many unknowns, esp. in the elderly. To the best of our knowledge, this is the first work that synthesizes and critically evaluates existing evidence on the possible assocn. between human gut microbiota and cognitive function in the elderly. For this purpose, comprehensive literature searches were conducted using the electronic databases PubMed, Google Scholar, and ScienceDirect. The gut microbiota of cognitively healthy and impaired elderly people may differ in the diversity and abundance of individual taxes, but specific taxes cannot be identified. However, some tendencies to changing the Firmicutes/Bacteroidetes ratio can be identified. Currently, clin. trials involving probiotics, prebiotics, and synbiotics supplementation have shown that there are premises for the claim that these factors can improve cognitive functions, however there is no single intervention beneficial to the elderly population. More reliable evidence from large-scale, long-period RCT is needed. Despite proposing several potential mechanisms of the gut microbiota's influence on the cognitive function impairment, prospective research on this topic is extremely difficult to conduct due to numerous confounding factors that may affect the gut microbiota. Heterogeneity of research outcomes impairs insight into these relations.
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533Munawar, N.; Ahsan, K.; Muhammad, K.; Ahmad, A.; Anwar, M. A.; Shah, I.; Al Ameri, A. K.; Al Mughairbi, F. Hidden role of gut microbiome dysbiosis in schizophrenia: Antipsychotics or psychobiotics as therapeutics?. Int. J. Mol. Sci. 2021, 22, 7671, DOI: 10.3390/ijms22147671Google Scholar533https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVWiurnI&md5=7826b70c91ab23b267058b2d5e8d2acbHidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics?Munawar, Nayla; Ahsan, Khansa; Muhammad, Khalid; Ahmad, Aftab; Anwar, Munir A.; Shah, Iltaf; Al Ameri, Ahlam Khalifa; Al Mughairbi, FadwaInternational Journal of Molecular Sciences (2021), 22 (14), 7671CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)A review. Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiol. Mounting evidence indicates the involvement of genetics and epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, and environmental influence in the disease, but a single root cause and mechanism involved has yet to be conclusively detd. Consequently, the identification of diagnostic markers and the development of psychotic drugs for the treatment of schizophrenia faces a high failure rate. This article surveys the etiol. of schizophrenia with a particular focus on gut microbiota regulation and the microbial signaling system that correlates with the brain through the vagus nerve, enteric nervous system, immune system, and prodn. of postbiotics. Gut microbially produced mols. may lay the groundwork for further investigations into the role of gut microbiota dysbiosis and the pathophysiol. of schizophrenia. Current treatment of schizophrenia is limited to psychotherapy and antipsychotic drugs that have significant side effects. Therefore, alternative therapeutic options merit exploration. The use of psychobiotics alone or in combination with antipsychotics may promote the development of novel therapeutic strategies. In view of the individual gut microbiome structure and personalized response to antipsychotic drugs, a tailored and targeted manipulation of gut microbial diversity naturally by novel prebiotics (non-digestible fiber) may be a successful alternative therapeutic for the treatment of schizophrenia patients.
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534Cohen Kadosh, K.; Basso, M.; Knytl, P.; Johnstone, N.; Lau, J. Y. F.; Gibson, G. R. Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultation. Transl Psychiatry 2021, 11, 352, DOI: 10.1038/s41398-021-01422-7Google Scholar534https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c7osFKjtA%253D%253D&md5=7cb3ed10800b0f4e82de45e83fc925a4Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultationCohen Kadosh Kathrin; Basso Melissa; Knytl Paul; Johnstone Nicola; Lau Jennifer Y F; Gibson Glenn RTranslational psychiatry (2021), 11 (1), 352 ISSN:.The human gut microbiome influence on brain function and mental health is an emerging area of intensive research. Animal and human research indicates adolescence as a sensitive period when the gut-brain axis is fine-tuned, where dietary interventions to change the microbiome may have long-lasting consequences for mental health. This study reports a systematic review and meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, with discussion of a consultation on the acceptability of psychobiotic interventions for mental health management amongst youth with lived experience. Six databases were searched for controlled trials in human samples (age range: 10-24 years) seeking to reduce anxiety. Post intervention outcomes were extracted as standard mean differences (SMDs) and pooled based on a random-effects model. 5416 studies were identified: 14 eligible for systematic review and 10 eligible for meta-analysis (total of 324 experimental and 293 control subjects). The meta-analysis found heterogeneity I(2) was 12% and the pooled SMD was -0.03 (95% CI: -0.21, 0.14), indicating an absence of effect. One study presented with low bias risk, 5 with high, and 4 with uncertain risk. Accounting for risk, sensitivities analysis revealed a SMD of -0.16 (95% CI: -0.38, 0.07), indicative of minimal efficacy of psychobiotics for anxiety treatment in humans. There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding, and addressing the wider context, and would be welcomed by anxious youths.
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535Osadchiy, V.; Martin, C. R.; Mayer, E. A. The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications. Clin. Gastroenterol. Hepatol. 2019, 17, 322– 332, DOI: 10.1016/j.cgh.2018.10.002Google Scholar535https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1ymsrbE&md5=d1132fc4ba579bf4cd053d30824a3ee6The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical ImplicationsOsadchiy, Vadim; Martin, Clair R.; Mayer, Emeran A.Clinical Gastroenterology and Hepatology (2019), 17 (2), 322-332CODEN: CGHLAW; ISSN:1542-3565. (Elsevier)A review. Based largely on results from preclin. studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.We reviewed the preclin. and clin. literature related to the topic of brain gut microbiome interactions.Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.
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536Cussotto, S.; Strain, C. R.; Fouhy, F.; Strain, R. G.; Peterson, V. L.; Clarke, G.; Stanton, C.; Dinan, T. G.; Cryan, J. F. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology (Berl.) 2019, 236, 1671– 1685, DOI: 10.1007/s00213-018-5006-5Google Scholar536https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3ivVOqtQ%253D%253D&md5=f6d5677771d94453b101efb585dd9f9eDifferential effects of psychotropic drugs on microbiome composition and gastrointestinal functionCussotto Sofia; Strain Conall R; Fouhy Fiona; Strain Ronan G; Peterson Veronica L; Clarke Gerard; Stanton Catherine; Dinan Timothy G; Cryan John F; Cussotto Sofia; Peterson Veronica L; Cryan John F; Strain Conall R; Fouhy Fiona; Strain Ronan G; Stanton Catherine; Clarke Gerard; Stanton Catherine; Dinan Timothy GPsychopharmacology (2019), 236 (5), 1671-1685 ISSN:.RATIONALE: Growing evidence supports a role for the microbiota in regulating gut-brain interactions and, thus, psychiatric disorders. Despite substantial scientific efforts to delineate the mechanism of action of psychotropic medications at a central nervous system (CNS) level, there remains a critical lack of understanding on how these drugs might affect the microbiota and gut physiology. OBJECTIVES: We investigated the antimicrobial activity of psychotropics against two bacterial strain residents in the human gut, Lactobacillus rhamnosus and Escherichia coli. In addition, we examined the impact of chronic treatment with these drugs on microbiota and intestinal parameters in the rat. RESULTS: In vitro fluoxetine and escitalopram showed differential antimicrobial effects. Lithium, valproate and aripiprazole administration significantly increased microbial species richness and diversity, while the other treatments were not significantly different from controls. At the genus level, several species belonging to Clostridium, Peptoclostridium, Intestinibacter and Christenellaceae were increased following treatment with lithium, valproate and aripiprazole when compared to the control group. Animals treated with escitalopram, venlafaxine, fluoxetine and aripiprazole exhibited an increased permeability in the ileum. CONCLUSIONS: These data show that psychotropic medications differentially influence the composition of gut microbiota in vivo and that fluoxetine and escitalopram have specific antimicrobial activity in vitro. Interestingly, drugs that significantly altered gut microbial composition did not increase intestinal permeability, suggesting that the two factors are not causally linked. Overall, unravelling the impact of psychotropics on gastrointestinal and microbiota measures offers the potential to provide critical insight into the mechanism of action and side effects of these medications.
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Abstract
Figure 1
Figure 1. Timeline of major research and development milestones related to the microbiome. (12−30,39,49−80)
Figure 2
Figure 2. Journal and patent publication trends on gut microbiome research related to mental and gut health according to the CAS Content Collection. Inset: microbiome vs proteome document yearly trends.
Figure 3
Figure 3. Top countries publishing journal articles (A) and patents (B) related to gut microbiome research in mental and gut health.
Figure 4
Figure 4. Flow of patent filings related to gut microbiome research in mental and gut health from different patent assignee locations (left) to various patent offices of filing (right). The abbreviations on the right indicate the patent offices of United States (US), Australia (AU), World Intellectual Property Organization (WO), Canada (CA), Austria (AT), European Patent Office (EP), Israel (IL), Norway (NO), Hong Kong (HK), Mexico (MX), Japan (JP), Brazil (BR), Spain (ES), India (IN), Russian Federation (RU), China (CN), and Korea (KR).
Figure 5
Figure 5. Key concepts in the scientific publications relevant to the gut microbiome research in mental and gut health. (A) Number of publications exploring key concepts related to gut microbiome research in mental and gut health. (B) Trends in key concepts presented in the articles related to gut microbiome research in mental and gut health during the years 2016–2021. Percentages are calculated with yearly publication numbers for each key concept, normalized by the total number of publications for the same concept in the same time period.
Figure 6
Figure 6. Gut-microbiota-participant bacteria.
Figure 7
Figure 7. Representation (as number of records) of the gut bacteria phyla and species in the CAS Content Collection.
Figure 8
Figure 8. Distribution of the publications in the CAS Content Collection related to gut microbiome-associated diseases.
Figure 9
Figure 9. Trends in the number of publications concerning gut microbiome-related diseases during the years 2016–2021. Percentages are calculated with yearly publication numbers for each disease, normalized by the total number of publications for the same disease in the same time period.
Figure 10
Figure 10. Correlation between major classes of gut bacteria with mental and gastrointestinal disorders, as reflected in the number of associated records in the CAS Content Collection.
Figure 11
Figure 11. Trends in the therapeutic strategies applied for the treatment of mental and gastrointestinal disorders, as presented in the documents related to gut microbiome research during the years 2017–2021. Percentages are calculated with yearly publication numbers for each type of therapeutic intervention normalized by the total number of publications for the same intervention in the same time period.
Figure 12
Figure 12. Exemplary gut microbiome metabolites and their mechanism of action in gut–brain communications.
Figure 13
Figure 13. Gut microbiome metabolite classes and their roles in digestive system functions.
Figure 14
Figure 14. Top universities, research institutes, and hospitals publications (1967–2022) related to gut microbiome research in mental and gastrointestinal health: (A) journal publications and (B) patents.
Figure 15
Figure 15. Overall capital raised and deal counts of venture capital investment for the prebiotic, probiotic, and the microbiome field ($) (source: pitchbook.com).
Figure 16
Figure 16. (Left) The percentage and number of analyzed global organizations utilizing probiotics for mental disorders and DGBI treatment. (Right) The percentage and number of analyzed global organizations utilizing prebiotics for mental disorders and DGBI treatment.
Figure 17
Figure 17. (Left) The percentage and number of analyzed global organizations utilizing postbiotics for mental disorders and DGBI treatment. (Right) The percentage and number of analyzed global organizations utilizing fecal transplant for mental disorders and DGBI treatment.
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References
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1Schopf, J. W. Disparate rates, differing fates: tempo and mode of evolution changed from the Precambrian to the Phanerozoic. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 6735– 6742, DOI: 10.1073/pnas.91.15.67351https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXlslGjtr4%253D&md5=31cf08a8c7c02f915feadc74ded5ef7bDisparate rates, differing fates: tempo and mode of evolution changed from the Precambrian to the PhanerozoicSchopf, J. WilliamProceedings of the National Academy of Sciences of the United States of America (1994), 91 (15), 6735-42CODEN: PNASA6; ISSN:0027-8424.Over the past quarter century, detailed genus- and species-level similarities in cellular morphol. between described taxa of Precambrian microfossils and extant cyanobacteria have been noted and regarded as biol. and taxonomically significant by numerous workers worldwide. Such similarities are particularly well documented for members of the Oscillatoriaceae and Chroococcaceae, the two most abundant and widespread Precambrian cyanobacterial families. For species of two addnl. families, the Entophysalidaceae and Pleurocapsaceae, species-level morphol. similarities are supported by in-depth fossil-modern comparisons of environment, taphonomy, development, and behavior. Morphol. and probably physiol. as well, such cyanobacterial "living fossils" have exhibited an extraordinarily slow (hypobradytelic) rate of evolutionary change, evidently a result of the broad ecol. tolerance characteristic of many members of the group and a striking example of G G. Simpson's [Simpson, G. G. (1944) Tempo and Mode in Evolution (Columbia Univ. Press, New York)] "rule of the survival of the relatively unspecialized.". In both tempo and mode of evolution, much of the Precambrian history of life-that dominated by microscopic cyanobacteria and related prokaryotes-appears to have differed markedly from the more recent Phanerozoic evolution of megascopic, horotelic, adaptationally specialized eukaryotes.
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2Averill, C.; Anthony, M. A.; Baldrian, P.; Finkbeiner, F.; van den Hoogen, J.; Kiers, T.; Kohout, P.; Hirt, E.; Smith, G. R.; Crowther, T. W. Defending Earth’s terrestrial microbiome. Nat. Microbiol. 2022, 7, 1717, DOI: 10.1038/s41564-022-01228-32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFCgurjP&md5=6f52ece9458ac70645ac49ffb979f409Defending Earth's terrestrial microbiomeAverill, Colin; Anthony, Mark A.; Baldrian, Petr; Finkbeiner, Felix; van den Hoogen, Johan; Kiers, Toby; Kohout, Petr; Hirt, Eliane; Smith, Gabriel Reuben; Crowther, Tom W.Nature Microbiology (2022), 7 (11), 1717-1725CODEN: NMAICH; ISSN:2058-5276. (Nature Portfolio)Abstr.: Microbial life represents the majority of Earth's biodiversity. Across disparate disciplines from medicine to forestry, scientists continue to discover how the microbiome drives essential, macro-scale processes in plants, animals and entire ecosystems. Yet, there is an emerging realization that Earth's microbial biodiversity is under threat. Here we advocate for the conservation and restoration of soil microbial life, as well as active incorporation of microbial biodiversity into managed food and forest landscapes, with an emphasis on soil fungi. We analyze 80 expts. to show that native soil microbiome restoration can accelerate plant biomass prodn. by 64% on av., across ecosystems. Enormous potential also exists within managed landscapes, as agriculture and forestry are the dominant uses of land on Earth. Along with improving and stabilizing yields, enhancing microbial biodiversity in managed landscapes is a crit. and underappreciated opportunity to build reservoirs, rather than deserts, of microbial life across our planet. As markets emerge to engineer the ecosystem microbiome, we can avert the mistakes of aboveground ecosystem management and avoid microbial monocultures of single high-performing microbial strains, which can exacerbate ecosystem vulnerability to pathogens and extreme events. Harnessing the planet's breadth of microbial life has the potential to transform ecosystem management, but it requires that we understand how to monitor and conserve the Earth's microbiome.
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3O’Hara, A. M.; Shanahan, F. The gut flora as a forgotten organ. EMBO reports 2006, 7, 688– 693, DOI: 10.1038/sj.embor.74007313https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XmsVanurg%253D&md5=4976fe244704b626436ac3ac00f28c99The gut flora as a forgotten organO'Hara, Ann M.; Shanahan, FergusEMBO Reports (2006), 7 (7), 688-693CODEN: ERMEAX; ISSN:1469-221X. (Nature Publishing Group)A review. The intestinal microflora is a pos. health asset that crucially influences the normal structural and functional development of the mucosal immune system. Mucosal immune responses to resident intestinal microflora require precise control and an immunosensory capacity for distinguishing commensal from pathogenic bacteria. In genetically susceptible individuals, some components of the flora can become a liability and contribute to the pathogenesis of various intestinal disorders, including inflammatory bowel diseases. It follows that manipulation of the flora to enhance the beneficial components represents a promising therapeutic strategy. The flora has a collective metabolic activity equal to a virtual organ within an organ, and the mechanisms underlying the conditioning influence of the bacteria on mucosal homeostasis and immune responses are beginning to be unravelled. An improved understanding of this hidden organ will reveal secrets that are relevant to human health and to several infectious, inflammatory and neoplastic disease processes.
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4Bäckhed, F.; Ley, R. E.; Sonnenburg, J. L.; Peterson, D. A.; Gordon, J. I. Host-bacterial mutualism in the human intestine. Science 2005, 307, 1915– 1920, DOI: 10.1126/science.11048164https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2M7lvVKlsg%253D%253D&md5=3f7557c5ea4d355c758e9bce97f544e9Host-bacterial mutualism in the human intestineBackhed Fredrik; Ley Ruth E; Sonnenburg Justin L; Peterson Daniel A; Gordon Jeffrey IScience (New York, N.Y.) (2005), 307 (5717), 1915-20 ISSN:.The distal human intestine represents an anaerobic bioreactor programmed with an enormous population of bacteria, dominated by relatively few divisions that are highly diverse at the strain/subspecies level. This microbiota and its collective genomes (microbiome) provide us with genetic and metabolic attributes we have not been required to evolve on our own, including the ability to harvest otherwise inaccessible nutrients. New studies are revealing how the gut microbiota has coevolved with us and how it manipulates and complements our biology in ways that are mutually beneficial. We are also starting to understand how certain keystone members of the microbiota operate to maintain the stability and functional adaptability of this microbial organ.
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5Cénit, M. C.; Matzaraki, V.; Tigchelaar, E. F.; Zhernakova, A. Rapidly expanding knowledge on the role of the gut microbiome in health and disease. Biochim. Biophys. Acta 2014, 1842, 1981– 1992, DOI: 10.1016/j.bbadis.2014.05.0235https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXpvVart74%253D&md5=46e82a3c41ac32b0a78c4c253b8365d9Rapidly expanding knowledge on the role of the gut microbiome in health and diseaseCenit, M. C.; Matzaraki, V.; Tigchelaar, E. F.; Zhernakova, A.Biochimica et Biophysica Acta, Molecular Basis of Disease (2014), 1842 (10), 1981-1992CODEN: BBADEX; ISSN:0925-4439. (Elsevier B. V.)A review. The human gut is colonized by a wide diversity of micro-organisms, which are now known to play a key role in the human host by regulating metabolic functions and immune homeostasis. Many studies have indicated that the genomes of the authors' gut microbiota, known as the gut microbiome or the authors' "other genome" could play an important role in immune-related, complex diseases, and growing evidence supports a causal role for gut microbiota in regulating predisposition to diseases. A comprehensive anal. of the human gut microbiome is thus important to unravel the exact mechanisms by which the gut microbiota are involved in health and disease. Recent advances in next-generation sequencing technol., along with the development of metagenomics and bioinformatics tools, have provided opportunities to characterize the microbial communities. Furthermore, studies using germ-free animals have shed light on how the gut microbiota are involved in autoimmunity. In this review the authors describe the different approaches used to characterize the human microbiome, review current knowledge about the gut microbiome, and discuss the role of gut microbiota in immune homeostasis and autoimmunity. Finally, the authors indicate how this knowledge could be used to improve human health by manipulating the gut microbiota. This article is part of a Special Issue entitled: From Genome to Function.
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6Vrancken, G.; Gregory, A. C.; Huys, G. R. B.; Faust, K.; Raes, J. Synthetic ecology of the human gut microbiota. Nature Reviews Microbiology 2019, 17, 754– 763, DOI: 10.1038/s41579-019-0264-86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvV2ktrbF&md5=d93899ca06271b82c58a83b2bfa455a9Synthetic ecology of the human gut microbiotaVrancken, Gino; Gregory, Ann C.; Huys, Geert R. B.; Faust, Karoline; Raes, JeroenNature Reviews Microbiology (2019), 17 (12), 754-763CODEN: NRMACK; ISSN:1740-1526. (Nature Research)Despite recent advances in sequencing and culturing, a deep knowledge of the wiring and functioning of the human gut ecosystem and its microbiota as a community is still missing. A holistic mechanistic understanding will require study of the gut microbiota as an interactive and spatially organized biol. system, which is difficult to do in complex natural communities. Synthetic gut microbial ecosystems can function as model systems to further current understanding of the compn., stability and functional activities of the microbiota. In this Review, we provide an overview of the current synthetic ecol. strategies that can be used towards a more comprehensive understanding of the human gut ecosystem. Such approaches that integrate in vitro expts. using cultured isolates with math. modeling will enable the ultimate goal: translating mechanistic and ecol. knowledge into novel and effective therapies.
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7Hasan, N.; Yang, H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019, 7, e7502, DOI: 10.7717/peerj.7502There is no corresponding record for this reference.
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8Pariente, N.; York, A. Milestones in human microbiota research. https://www.nature.com/immersive/d42859-019-00041-z/index.html (accessed October 6, 2022).There is no corresponding record for this reference.
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9Malla, M. A.; Dubey, A.; Kumar, A.; Yadav, S.; Hashem, A.; Abd_Allah, E. F. Exploring the Human Microbiome: The Potential Future Role of Next-Generation Sequencing in Disease Diagnosis and Treatment. Front. Immunol. 2019, 9, 02868, DOI: 10.3389/fimmu.2018.02868There is no corresponding record for this reference.
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10Berg, G.; Rybakova, D.; Fischer, D.; Cernava, T.; Vergès, M.-C. C.; Charles, T.; Chen, X.; Cocolin, L.; Eversole, K.; Corral, G. H. Microbiome definition re-visited: old concepts and new challenges. Microbiome 2020, 8, 103, DOI: 10.1186/s40168-020-00875-010https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38nms1Sgug%253D%253D&md5=834e4c5e1470b19c81ccbbaf181b37d1Microbiome definition re-visited: old concepts and new challengesBerg Gabriele; Rybakova Daria; Cernava Tomislav; Fischer Doreen; Schloter Michael; Verges Marie-Christine Champomier; Maguin Emmanuelle; Charles Trevor; Charles Trevor; Chen Xiaoyulong; Cocolin Luca; Schelkle Bettina; Eversole Kellye; Corral Gema Herrero; Kazou Maria; Kinkel Linda; Lange Lene; Lima Nelson; Loy Alexander; Wagner Michael; Macklin James A; Mauchline Tim; McClure Ryan; Mitter Birgit; Sessitsch Angela; Ryan Matthew; Sarand Inga; Smidt Hauke; van Overbeek Leo; Roume Hugo; Kiran G Seghal; Selvin Joseph; Souza Rafael Soares Correa de; Singh Brajesh K; Singh Brajesh K; Walsh AaronMicrobiome (2020), 8 (1), 103 ISSN:.The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term "microbiome." Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role. Video Abstract.
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11Butler, M. I.; Mörkl, S.; Sandhu, K. V.; Cryan, J. F.; Dinan, T. G. The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Santé Mentale: que Devrions-Nous dire à nos Patients?. Can. J. Psychiatry. 2019, 64, 747– 760, DOI: 10.1177/070674371987416811https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mrps1KlsA%253D%253D&md5=bd5b0b7edcb3e31a64274c036a7bee18The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Sante Mentale : que Devrions-Nous dire a nos Patients?Butler Mary I; Morkl Sabrina; Dinan Timothy G; Morkl Sabrina; Sandhu Kiran V; Cryan John FCanadian journal of psychiatry. Revue canadienne de psychiatrie (2019), 64 (11), 747-760 ISSN:.The gut microbiome as a potential therapeutic target for mental illness is a hot topic in psychiatry. Trillions of bacteria reside in the human gut and have been shown to play a crucial role in gut-brain communication through an influence on neural, immune, and endocrine pathways. Patients with various psychiatric disorders including depression, bipolar disorder, schizophrenia, and autism spectrum disorder have been shown to have significant differences in the composition of their gut microbiome. Enhancing beneficial bacteria in the gut, for example, through the use of probiotics, prebiotics, or dietary change, has the potential to improve mood and reduce anxiety in both healthy people and patient groups. Much attention is being given to this subject in the general media, and patients are becoming increasingly interested in the potential to treat mental illness with microbiome-based therapies. It is imperative that those working with people with mental illness are aware of the rationale and current evidence base for such treatment strategies. In this review, we provide an overview of the gut microbiome, what it is, and what it does in relation to gut-brain communication and psychological function. We describe the fundamental principles and basic techniques used in microbiome-gut-brain axis research in an accessible way for a clinician audience. We summarize the current evidence in relation to microbiome-based strategies for various psychiatric disorders and provide some practical advice that can be given to patients seeking to try a probiotic for mental health benefit.
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12Corliss, J. O. Three Centuries of Protozoology: A Brief Tribute to its Founding Father, A. van Leeuwenhoek of Delft. Journal of Protozoology 1975, 22, 3– 7, DOI: 10.1111/j.1550-7408.1975.tb00934.x12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaE2M7hs1GhtQ%253D%253D&md5=879a6323e91fa81ac855aad29b9a525bThree centuries of protozoology: a brief tribute to its founding father, A. van Leeuwenhoek of DelftCorliss J OThe Journal of protozoology (1975), 22 (1), 3-7 ISSN:0022-3921.It was exactly 300 years ago this month (August 1974) that the 17th century modest draper from Delft, Holland--Antony van Leeuwenhoek--discovered protozoa. Describing them, often with amazing accuracy considering the optical equipment he was using (simply a home-made "glorified" hand lens), in letters to the Royal Society of London, he established himself, certainly, as the founding father of protozoology. It is particularly appropriate for an assemblage of protozoologists to pay homage to this intrepid "philosopher in little things," a man with an insatiable curiosity about his wee animalcules, on the tricentenary of his discovery of them, since it was an event of such long-lasting significance.
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13Leidy, J. A flora and fauna within living animals. Smithsonian Institution: WA, 1853.There is no corresponding record for this reference.
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14Savage, D. C. Microbial biota of the human intestine: a tribute to some pioneering scientists. Curr. Issues Intest. Microbiol. 2001, 2, 1– 1514https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3MnmsVOlsw%253D%253D&md5=75a3c7bab223cbc390e38f4b8d9644daMicrobial biota of the human intestine: a tribute to some pioneering scientistsSavage D CCurrent issues in intestinal microbiology (2001), 2 (1), 1-15 ISSN:1466-531X.Research on the indigenous intestinal microbiota of man was initiated well before the end of the 19th Century. The work continued at a slow but steady pace throughout the first half of the 20th Century. Findings from the effort had little impact on medicine and other aspects of human biology, however, until the 6th decade of the 20th Century. During that decade, research in the area was begun by eight groups of investigators, each of which was led by one or two senior scientists with great experimental talent, creativity and foresight. Their findings added new dimension to knowledge of the microbiota and initiated an explosion of interest in research in the field that has continued to the present day. The research of the groups during the 1960's is described in this review as a tribute to the senior scientists who had such critical impact on this important field of study.
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15Pariente, N. A field is born. 2019. https://www.nature.com/articles/d42859-019-00006-2.There is no corresponding record for this reference.
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16Micheli, P. A. Nova plantarum genera iuxta Tournefortii methodum disposita ; 1729.There is no corresponding record for this reference.
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17Drews, G. The roots of microbiology and the influence of Ferdinand Cohn on microbiology of the 19th century. FEMS Microbiol. Rev. 2000, 24, 225– 249, DOI: 10.1111/j.1574-6976.2000.tb00540.x17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXjslOru7g%253D&md5=402d7cf8cd6b2bf3509d72761ad9e6a9The roots of microbiology and the influence of Ferdinand Cohn on microbiology of the 19th centuryDrews, G.FEMS Microbiology Reviews (2000), 24 (3), 225-249CODEN: FMREE4; ISSN:0168-6445. (Elsevier Science B.V.)The beginning of modern microbiol. can be traced back to the 1870s, and it was based on the development of new concepts that originated during the two preceding centuries on the role of microorganisms, new exptl. methods, and discoveries in chem., physics, and evolutionary cell biol. The crucial progress was the isolation and growth on solid media of clone cultures arising from single cells and the demonstration that these pure cultures have specific, inheritable characteristics and metabolic capacities. The doctrine of the spontaneous generation of microorganisms, which stimulated research for a century, lost its role as an important concept. Microorganisms were discovered to be causative agents of infectious diseases and of specific metabolic processes. Microscopy techniques advanced studies on microorganisms. The discovery of sexuality and development in microorganisms and Darwin's theory of evolution contributed to the founding of microbiol. as a science. Ferdinand Cohn (1828-1898), a pioneer in the developmental biol. of lower plants, considerably promoted the taxonomy and physiol. of bacteria, discovered the heat-resistant endospores of bacilli, and was active in applied microbiol.
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18Boundless. Koch’s Postulates. https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/10%3A_Epidemiology/10.1%3A_Principles_of_Epidemiology/10.1D%3A__Kochs_Postulates (accessed October 6, 2022).There is no corresponding record for this reference.
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19Metchnikoff, E. Prolongation of Life: Optimistic Studies ; 1923.There is no corresponding record for this reference.
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20Sonnenborn, U. Escherichia coli strain Nissle 1917─from bench to bedside and back: history of a special Escherichia coli strain with probiotic properties. FEMS Microbiol. Lett. 2016, 363, fnw212, DOI: 10.1093/femsle/fnw212There is no corresponding record for this reference.
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21Tan, S. Y.; Tatsumura, Y. Alexander Fleming (1881–1955): Discoverer of penicillin. Singapore Med. J. 2015, 56, 366– 367, DOI: 10.11622/smedj.201510521https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC287gtVKisQ%253D%253D&md5=49579a42a8642f0f8f09c8c49e00a60eAlexander Fleming (1881-1955): Discoverer of penicillinTan Siang Yong; Tatsumura YvonneSingapore medical journal (2015), 56 (7), 366-7 ISSN:0037-5675.There is no expanded citation for this reference.
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22Almeida, A.; Mitchell, A. L.; Boland, M.; Forster, S. C.; Gloor, G. B.; Tarkowska, A.; Lawley, T. D.; Finn, R. D. A new genomic blueprint of the human gut microbiota. Nature 2019, 568, 499– 504, DOI: 10.1038/s41586-019-0965-122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmslKhu7s%253D&md5=4871997c22d8542f9df02ad2c0066e61A new genomic blueprint of the human gut microbiotaAlmeida, Alexandre; Mitchell, Alex L.; Boland, Miguel; Forster, Samuel C.; Gloor, Gregory B.; Tarkowska, Aleksandra; Lawley, Trevor D.; Finn, Robert D.Nature (London, United Kingdom) (2019), 568 (7753), 499-504CODEN: NATUAS; ISSN:0028-0836. (Nature Research)The compn. of the human gut microbiota is linked to health and disease, but knowledge of individual microbial species is needed to decipher their biol. roles. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. We identify 1952 uncultured candidate bacterial species by reconstructing 92,143 metagenome-assembled genomes from 11,850 human gut microbiomes. These uncultured genomes substantially expand the known species repertoire of the collective human gut microbiota, with a 281% increase in phylogenetic diversity. Although the newly identified species are less prevalent in well-studied populations compared to ref. isolate genomes, they improve classification of understudied African and South American samples by >200%. These candidate species encode hundreds of newly identified biosynthetic gene clusters and possess a distinctive functional capacity that might explain their elusive nature. Our work expands the known diversity of uncultured gut bacteria, which provides unprecedented resoln. for taxonomic and functional characterization of the intestinal microbiota.
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23Hungate, R. E., Chapter IV A Roll Tube Method for Cultivation of Strict Anaerobes. In Methods in Microbiology, Vol. 3; Norris, J. R., Ribbons, D. W., Eds.; Academic Press, 1969; pp 117– 132.There is no corresponding record for this reference.
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24Cat, L. A. The Decade Of The Microbiome. https://www.forbes.com/sites/linhanhcat/2019/12/31/decade-of-the-microbiome/?sh=7e621a679961 (accessed October 11, 2022).There is no corresponding record for this reference.
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25NIH Human Microbiome Project. https://www.hmpdacc.org/overview/ (accessed October 6, 2022).There is no corresponding record for this reference.
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26MetaHIT. https://www.gutmicrobiotaforhealth.com/metahit/ (accessed October 6, 2022).There is no corresponding record for this reference.
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27Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K. S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464, 59– 65, DOI: 10.1038/nature0882127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXislahsLc%253D&md5=7116690033a12ae47bbe53c77f768e91A human gut microbial gene catalogue established by metagenomic sequencingQin, Junjie; Li, Ruiqiang; Raes, Jeroen; Arumugam, Manimozhiyan; Burgdorf, Kristoffer Solvsten; Manichanh, Chaysavanh; Nielsen, Trine; Pons, Nicolas; Levenez, Florence; Yamada, Takuji; Mende, Daniel R.; Li, Junhua; Xu, Junming; Li, Shaochuan; Li, Dongfang; Cao, Jianjun; Wang, Bo; Liang, Huiqing; Zheng, Huisong; Xie, Yinlong; Tap, Julien; Lepage, Patricia; Bertalan, Marcelo; Batto, Jean-Michel; Hansen, Torben; Le Paslier, Denis; Linneberg, Allan; Nielsen, H. Bjoern; Pelletier, Eric; Renault, Pierre; Sicheritz-Ponten, Thomas; Turner, Keith; Zhu, Hongmei; Yu, Chang; Li, Shengting; Jian, Min; Zhou, Yan; Li, Yingrui; Zhang, Xiuqing; Li, Songgang; Qin, Nan; Yang, Huanming; Wang, Jian; Brunak, Soeren; Dore, Joel; Guarner, Francisco; Kristiansen, Karsten; Pedersen, Oluf; Parkhill, Julian; Weissenbach, Jean; Antolin, Maria; Artiguenave, Francois; Blottiere, Herve; Borruel, Natalia; Bruls, Thomas; Casellas, Francesc; Chervaux, Christian; Cultrone, Antonella; Delorme, Christine; Denariaz, Gerard; Dervyn, Rozenn; Forte, Miguel; Friss, Carsten; van de Guchte, Maarten; Guedon, Eric; Haimet, Florence; Jamet, Alexandre; Juste, Catherine; Kaci, Ghalia; Kleerebezem, Michiel; Knol, Jan; Kristensen, Michel; Layec, Severine; Le Roux, Karine; Leclerc, Marion; Maguin, Emmanuelle; Melo Minardi, Raquel; Oozeer, Raish; Rescigno, Maria; Sanchez, Nicolas; Tims, Sebastian; Torrejon, Toni; Varela, Encarna; de Vos, Willem; Winogradsky, Yohanan; Zoetendal, Erwin; Bork, Peer; Ehrlich, S. Dusko; Wang, JunNature (London, United Kingdom) (2010), 464 (7285), 59-65CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. This report describes the Illumina-based metagenomic sequencing, assembly, and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from fecal samples of 124 European individuals. The gene set, ∼150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbors between 1000 and 1150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. The minimal gut metagenome and the minimal gut bacterial genome are defined and described in terms of functions present in all individuals and most bacteria, resp. Sequence data are deposited in the European Short Read Archive with accession no. ERA000116.
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28Proctor, Lita M. The Human Microbiome Project in 2011 and Beyond. Cell Host Microbe 2011, 10, 287– 291, DOI: 10.1016/j.chom.2011.10.00128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlKisbbL&md5=ca57d3202f3891c261a4b3c7b7d449daThe Human Microbiome Project in 2011 and BeyondProctor, Lita M.Cell Host & Microbe (2011), 10 (4), 287-291CODEN: CHMECB; ISSN:1931-3128. (Cell Press)A review. The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. The authors highlight Human Microbiome Project (HMP) resources, including 600 microbial ref. genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed.
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29Birney, E.; Stamatoyannopoulos, J. A.; Dutta, A.; Guigó, R.; Gingeras, T. R.; Margulies, E. H.; Weng, Z.; Snyder, M.; Dermitzakis, E. T.; Stamatoyannopoulos, J. A. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007, 447, 799– 816, DOI: 10.1038/nature0587429https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXms1Wjsb0%253D&md5=727de4c5a83d3f75af54e31f974472a7Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectBirney, Ewan; Stamatoyannopoulos, John A.; Dutta, Anindya; Guigo, Roderic; Gingeras, Thomas R.; Margulies, Elliott H.; Weng, Zhiping; Snyder, Michael; Dermitzakis, Emmanouil T.; Stamatoyannopoulos, John A.; Thurman, Robert E.; Kuehn, Michael S.; Taylor, Christopher M.; Neph, Shane; Koch, Christoph M.; Asthana, Saurabh; Malhotra, Ankit; Adzhubei, Ivan; Greenbaum, Jason A.; Andrews, Robert M.; Flicek, Paul; Boyle, Patrick J.; Cao, Hua; Carter, Nigel P.; Clelland, Gayle K.; Davis, Sean; Day, Nathan; Dhami, Pawandeep; Dillon, Shane C.; Dorschner, Michael O.; Fiegler, Heike; Giresi, Paul G.; Goldy, Jeff; Hawrylycz, Michael; Haydock, Andrew; Humbert, Richard; James, Keith D.; Johnson, Brett E.; Johnson, Ericka M.; Frum, Tristan T.; Rosenzweig, Elizabeth R.; Karnani, Neerja; Lee, Kirsten; Lefebvre, Gregory C.; Navas, Patrick A.; Neri, Fidencio; Parker, Stephen C. J.; Sabo, Peter J.; Sandstrom, Richard; Shafer, Anthony; Vetrie, David; Weaver, Molly; Wilcox, Sarah; Yu, Man; Collins, Francis S.; Dekker, Job; Lieb, Jason D.; Tullius, Thomas D.; Crawford, Gregory E.; Sunyaev, Shamil; Noble, William S.; Dunham, Ian; Dutta, Anindya; Guigo, Roderic; Denoeud, France; Reymond, Alexandre; Kapranov, Philipp; Rozowsky, Joel; Zheng, Deyou; Castelo, Robert; Frankish, Adam; Harrow, Jennifer; Ghosh, Srinka; Sandelin, Albin; Hofacker, Ivo L.; Baertsch, Robert; Keefe, Damian; Flicek, Paul; Dike, Sujit; Cheng, Jill; Hirsch, Heather A.; Sekinger, Edward A.; Lagarde, Julien; Abril, Josep F.; Shahab, Atif; Flamm, Christoph; Fried, Claudia; Hackermueller, Joerg; Hertel, Jana; Lindemeyer, Manja; Missal, Kristin; Tanzer, Andrea; Washietl, Stefan; Korbel, Jan; Emanuelsson, Olof; Pedersen, Jakob S.; Holroyd, Nancy; Taylor, Ruth; Swarbreck, David; Matthews, Nicholas; Dickson, Mark C.; Thomas, Daryl J.; Weirauch, Matthew T.; Gilbert, James; Drenkow, Jorg; Bell, Ian; Zhao, Xiao Dong; Srinivasan, K. G.; Sung, Wing-Kin; Ooi, Hong Sain; Chiu, Kuo Ping; Foissac, Sylvain; Alioto, Tyler; Brent, Michael; Pachter, Lior; Tress, Michael L.; Valencia, Alfonso; Choo, Siew Woh; Choo, Chiou Yu; Ucla, Catherine; Manzano, Caroline; Wyss, Carine; Cheung, Evelyn; Clark, Taane G.; Brown, James B.; Ganesh, Madhavan; Patel, Sandeep; Tammana, Hari; Chrast, Jacqueline; Henrichsen, Charlotte N.; Kai, Chikatoshi; Kawai, Jun; Nagalakshmi, Ugrappa; Wu, Jiaqian; Lian, Zheng; Lian, Jin; Newburger, Peter; Zhang, Xueqing; Bickel, Peter; Mattick, John S.; Carninci, Piero; Hayashizaki, Yoshihide; Weissman, Sherman; Dermitzakis, Emmanouil T.; Margulies, Elliott H.; Hubbard, Tim; Myers, Richard M.; Rogers, Jane; Stadler, Peter F.; Lowe, Todd M.; Wei, Chia-Lin; Ruan, Yijun; Snyder, Michael; Birney, Ewan; Struhl, Kevin; Gerstein, Mark; Antonarakis, Stylianos E.; Gingeras, Thomas R.; Brown, James B.; Flicek, Paul; Fu, Yutao; Keefe, Damian; Birney, Ewan; Denoeud, France; Gerstein, Mark; Green, Eric D.; Kapranov, Philipp; Karaoez, Ulas; Myers, Richard M.; Noble, William S.; Reymond, Alexandre; Rozowsky, Joel; Struhl, Kevin; Siepel, Adam; Stamatoyannopoulos, John A.; Taylor, Christopher M.; Taylor, James; Thurman, Robert E.; Tullius, Thomas D.; Washietl, Stefan; Zheng, Deyou; Liefer, Laura A.; Wetterstrand, Kris A.; Good, Peter J.; Feingold, Elise A.; Guyer, Mark S.; Collins, Francis S.; Margulies, Elliott H.; Cooper, Gregory M.; Asimenos, George; Thomas, Daryl J.; Dewey, Colin N.; Siepel, Adam; Birney, Ewan; Keefe, Damian; Hou, Minmei; Taylor, James; Nikolaev, Sergey; Montoya-Burgos, Juan I.; Loeytynoja, Ari; Whelan, Simon; Pardi, Fabio; Massingham, Tim; Brown, James B.; Huang, Haiyan; Zhang, Nancy R.; Bickel, Peter; Holmes, Ian; Mullikin, James C.; Ureta-Vidal, Abel; Paten, Benedict; Seringhaus, Michael; Church, Deanna; Rosenbloom, Kate; Kent, W. James; Stone, Eric A.; Gerstein, Mark; Antonarakis, Stylianos E.; Batzoglou, Serafim; Goldman, Nick; Hardison, Ross C.; Haussler, David; Miller, Webb; Pachter, Lior; Green, Eric D.; Sidow, Arend; Weng, Zhiping; Trinklein, Nathan D.; Fu, Yutao; Zhang, Zhengdong D.; Karaoez, Ulas; Barrera, Leah; Stuart, Rhona; Zheng, Deyou; Ghosh, Srinka; Flicek, Paul; King, David C.; Taylor, James; Ameur, Adam; Enroth, Stefan; Bieda, Mark C.; Koch, Christoph M.; Hirsch, Heather A.; Wei, Chia-Lin; Cheng, Jill; Kim, Jonghwan; Bhinge, Akshay A.; Giresi, Paul G.; Jiang, Nan; Liu, Jun; Yao, Fei; Sung, Wing-Kin; Chiu, Kuo Ping; Vega, Vinsensius B.; Lee, Charlie W. H.; Ng, Patrick; Shahab, Atif; Sekinger, Edward A.; Yang, Annie; Moqtaderi, Zarmik; Zhu, Zhou; Xu, Xiaoqin; Squazzo, Sharon; Oberley, Matthew J.; Inman, David; Singer, Michael A.; Richmond, Todd A.; Munn, Kyle J.; Rada-Iglesias, Alvaro; Wallerman, Ola; Komorowski, Jan; Clelland, Gayle K.; Wilcox, Sarah; Dillon, Shane C.; Andrews, Robert M.; Fowler, Joanna C.; Couttet, Phillippe; James, Keith D.; Lefebvre, Gregory C.; Bruce, Alexander W.; Dovey, Oliver M.; Ellis, Peter D.; Dhami, Pawandeep; Langford, Cordelia F.; Carter, Nigel P.; Vetrie, David; Kapranov, Philipp; Nix, David A.; Bell, Ian; Patel, Sandeep; Rozowsky, Joel; et al.Nature (London, United Kingdom) (2007), 447 (7146), 799-816CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)We report the generation and anal. of functional data from multiple, diverse expts. performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a no. of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examn. of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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30Riesenfeld, C. S.; Schloss, P. D.; Handelsman, J. Metagenomics: Genomic Analysis of Microbial Communities. Annu. Rev. Genet. 2004, 38, 525– 552, DOI: 10.1146/annurev.genet.38.072902.09121630https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXltlyjtg%253D%253D&md5=84d6562bb905baacfe91982a2151722dMetagenomics: Genomic analysis of microbial communitiesRiesenfeld, Christian S.; Schloss, Patrick D.; Handelsman, JoAnnual Review of Genetics (2004), 38 (), 525-552CODEN: ARVGB7; ISSN:0066-4197. (Annual Reviews Inc.)A review. Uncultured microorganisms comprise the majority of the planet's biol. diversity. Microorganisms represent two of the three domains of life and contain vast diversity that is the product of an estd. 3.8 billion years of evolution. In many environments, as many as 99% of the microorganisms cannot be cultured by std. techniques, and the uncultured fraction includes diverse organisms that are only distantly related to the cultured ones. Therefore, culture-independent methods are essential to understand the genetic diversity, population structure, and ecol. roles of the majority of microorganisms. Metagenomics, or the culture-independent genomic anal. of an assemblage of microorganisms, has potential to answer fundamental questions in microbial ecol. This review describes progress toward understanding the biol. of uncultured Bacteria, Archaea, and viruses through metagenomic analyses.
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31Jandhyala, S. M.; Talukdar, R.; Subramanyam, C.; Vuyyuru, H.; Sasikala, M.; Nageshwar Reddy, D. Role of the normal gut microbiota. World J. Gastroenterol. 2015, 21, 8787– 8803, DOI: 10.3748/wjg.v21.i29.878731https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XosVSlsw%253D%253D&md5=b0cd06c0ec390547e6248afb8e782139Role of the normal gut microbiotaJandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Reddy, D. NageshwarWorld Journal of Gastroenterology (2015), 21 (29), 8787-8803CODEN: WJGAF2; ISSN:2219-2840. (Baishideng Publishing Group Inc.)Relation between the gut microbiota and human health is being increasingly recognized. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metab., xenobiotic and drug metab., maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like mols. that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.
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32Tomas, J.; Wrzosek, L.; Bouznad, N.; Bouet, S.; Mayeur, C.; Noordine, M. L.; Honvo-Houeto, E.; Langella, P.; Thomas, M.; Cherbuy, C. Primocolonization is associated with colonic epithelial maturation during conventionalization. FASEB J. 2013, 27, 645– 655, DOI: 10.1096/fj.12-21686132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXit1Skur0%253D&md5=311f2c67cbf2a56fdc02893385a4190bPrimocolonization is associated with colonic epithelial maturation during conventionalizationTomas, Julie; Wrzosek, Laura; Bouznad, Nassim; Bouet, Stephan; Mayeur, Camille; Noordine, Marie-Louise; Honvo-Houeto, Edith; Langella, Philippe; Thomas, Muriel; Cherbuy, ClaireFASEB Journal (2013), 27 (2), 645-655, 10.1096/fj.12-216861CODEN: FAJOEC; ISSN:0892-6638. (Federation of American Societies for Experimental Biology)Interaction between the gut microbiota and the host starts immediately after birth with the progressive colonization of the sterile intestine. Our aim was to investigate the interactions taking place in the colonic epithelium after the first exposure to gut microbiota. Germ-free (GF) rats were inoculated with two different microbiotas: the first, obtained from suckling rats, was rich in primocolonizing bacteria and the second, obtained from adult rats, was representative of a mature microbiota. Once transferred into GF rats, these two microbiotas evolved such that they converged, and recapitulated the primocolonization pattern, mimicking the chronol. scheme of implantation following birth. The two microbiotas induced common responses in the colonic epithelium: a transitory proliferative phase followed by a compensatory phase characterized by increases in the abundance of p21Cip1 and p27Kip1 and in the no. of goblet cells. The effects of the two microbiotas diverged only through their effects on colonic transporters. Analyses of solute carriers and aquaporins revealed that functional maturation was more pronounced following exposure to adult microbiota than suckling microbiota. The colon matured in parallel with the evolution of the microbiota compn., and we therefore suggest a link between intestinal events regulating homeostasis of the colon and modulation of microbial compn.
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33Caballero, S.; Pamer, E. G. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu. Rev. Immunol. 2015, 33, 227– 256, DOI: 10.1146/annurev-immunol-032713-12023833https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVSisL3M&md5=9f613a189ee2cb8447e3e7330eb4bc4dMicrobiota-Mediated Inflammation and Antimicrobial Defense in the IntestineCaballero, Silvia; Pamer, Eric G.Annual Review of Immunology (2015), 33 (), 227-256CODEN: ARIMDU; ISSN:0732-0582. (Annual Reviews)The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucleic acid sequencing platforms, new computational and bioinformatics tools, and full-genome characterization of several hundred commensal bacterial species facilitated studies of the microbiota and revealed that differences in microbiota compn. can be assocd. with inflammatory, metabolic, and infectious diseases, that each human is colonized by a distinct bacterial flora, and that the microbiota can be manipulated to reduce and even cure some diseases. Different bacterial species induce distinct immune cell populations that can play pro- and anti-inflammatory roles, and thus the compn. of the microbiota dets., in part, the level of resistance to infection and susceptibility to inflammatory diseases. This review summarizes recent work characterizing commensal microbes that contribute to the antimicrobial defense/inflammation axis.
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34Magnúsdóttir, S.; Ravcheev, D.; de Crécy-Lagard, V.; Thiele, I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Frontiers in Genetics 2015, 6, 148, DOI: 10.3389/fgene.2015.0014834https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MfgvVWltA%253D%253D&md5=4f500bfea9a3f72d0e88539d7e3ccfcfSystematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbesMagnusdottir Stefania; Ravcheev Dmitry; Thiele Ines; de Crecy-Lagard ValerieFrontiers in genetics (2015), 6 (), 148 ISSN:1664-8021.The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40-65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements.
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35Mayer, E. A.; Knight, R.; Mazmanian, S. K.; Cryan, J. F.; Tillisch, K. Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 2014, 34, 15490– 15496, DOI: 10.1523/JNEUROSCI.3299-14.201435https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2M3nvVKktw%253D%253D&md5=94069bb4e4d54c2afed184e28851a2c6Gut microbes and the brain: paradigm shift in neuroscienceMayer Emeran A; Knight Rob; Mazmanian Sarkis K; Cryan John F; Tillisch KirstenThe Journal of neuroscience : the official journal of the Society for Neuroscience (2014), 34 (46), 15490-6 ISSN:.The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject.
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36Clarke, G.; Grenham, S.; Scully, P.; Fitzgerald, P.; Moloney, R. D.; Shanahan, F.; Dinan, T. G.; Cryan, J. F. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 2013, 18, 666– 673, DOI: 10.1038/mp.2012.7736https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXot1aku7w%253D&md5=46c3ff1746ad758d4af322c058f8b4cbThe microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent mannerClarke, G.; Grenham, S.; Scully, P.; Fitzgerald, P.; Moloney, R. D.; Shanahan, F.; Dinan, T. G.; Cryan, J. F.Molecular Psychiatry (2013), 18 (6), 666-673CODEN: MOPSFQ; ISSN:1359-4184. (Nature Publishing Group)Bacterial colonization of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclin. tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concn. of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonized control animals. Moreover, this alteration is sex specific in contrast with the immunol. and neuroendocrine effects which are evident in both sexes. Concns. of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonization of the GF animals post weaning is insufficient to reverse the CNS neurochem. consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addn., reduced anxiety in GF animals is also normalized following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochem., but not behavioral, profile is resistant to restoration of a normal gut flora in later life. Mol. Psychiatry (2013) 18, 666-673; doi:10.1038/mp.2012.77; published online 12 June 2012.
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37Bray, N. The microbiota–gut–brain axis. https://www.nature.com/articles/d42859-019-00021-3 (accessed October 6, 2022).There is no corresponding record for this reference.
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38Dinan, T. G.; Cryan, J. F. The impact of gut microbiota on brain and behaviour: implications for psychiatry. Curr. Opin. Clin. Nutr. Metab. Care 2015, 18, 552– 558, DOI: 10.1097/MCO.000000000000022138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC283itlCitw%253D%253D&md5=66e25889e8960eb947e2384e8782ebb3The impact of gut microbiota on brain and behaviour: implications for psychiatryDinan Timothy G; Cryan John FCurrent opinion in clinical nutrition and metabolic care (2015), 18 (6), 552-8 ISSN:.PURPOSE OF REVIEW: The gut microbiota has become a focus of research for those interested in the brain and behaviour. Here, we profile the gut microbiota in a variety of neuropsychiatric syndromes. RECENT FINDINGS: Multiple routes of communication between the gut and brain have been established and these include the vagus nerve, immune system, short chain fatty acids and tryptophan. Developmentally, those born by caesarean section have a distinctly different microbiota in early life to those born per vaginum. At the other extreme, individuals who age with considerable ill-heath tend to show narrowing in microbial diversity. Recently, the gut microbiota has been profiled in a variety of conditions including autism, major depression and Parkinson's disease. There is still debate as to whether or not these changes are core to the pathophysiology or merely epiphenomenal. SUMMARY: The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.
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39Bravo, J. A.; Forsythe, P.; Chew, M. V.; Escaravage, E.; Savignac, H. M.; Dinan, T. G.; Bienenstock, J.; Cryan, J. F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 16050– 16055, DOI: 10.1073/pnas.110299910839https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1ekt7nF&md5=f87375fac8abc7761ef696afb9b42a59Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerveBravo, Javier A.; Forsythe, Paul; Chew, Marianne V.; Escaravage, Emily; Savignac, Helene M.; Dinan, Timothy G.; Bienenstock, John; Cryan, Ohn F.Proceedings of the National Academy of Sciences of the United States of America (2011), 108 (38), 16050-16055, S16050/1-S16050/7CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiol. and psychol. processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant redns. in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addn., L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone. and anxiety- and depression-related behavior. Moreover, the neurochem. and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress- related disorders such as anxiety and depression.
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40Cohen-Sacks, H.; Elazar, V.; Gao, J.; Golomb, A.; Adwan, H.; Korchov, N.; Levy, R. J.; Berger, M. R.; Golomb, G. Delivery and expression of pDNA embedded in collagen matrices. J. Controlled Release 2004, 95, 309– 320, DOI: 10.1016/j.jconrel.2003.11.00140https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhsVCms7w%253D&md5=7cee5279df6c140cab54b64d33b4bb13Delivery and expression of pDNA embedded in collagen matricesCohen-Sacks, Hagit; Elazar, Victoria; Gao, Jianchuan; Golomb, Assaf; Adwan, Hassan; Korchov, Nikoly; Levy, Robert J.; Berger, Martin R.; Golomb, GershonJournal of Controlled Release (2004), 95 (2), 309-320CODEN: JCREEC; ISSN:0168-3659. (Elsevier)Collagen matrixes can be used as non-viral biocompatible gene carriers for localized implantable gene therapy. Collagen matrixes embedding pDNA with enhanced binding through condensing agent linkage to the matrix or to the pDNA have been formulated, and characterized in various systems. PDNA and condensed pDNA were released intact from the matrixes within 1-2 days. In vitro transfection with collagen matrixes contg. pDNA (luciferase encoding), pDNA in liposome (LIP), and pDNA with polyethylenimine (PEI) resulted in significantly higher expression levels in comparison to naked pDNA. PDNA-LIP matrixes exhibited a dose response transfection of NIH 3T3, 293, MDA-MB-231 and smooth muscle cells (SMCs) in cell cultures. Subdermal implantations of collagen-polylysine-pDNA matrixes in rats resulted in significantly higher gene expression levels in comparison to non-condensed pDNA matrixes. Perivascular treatment with pDNA matrix and of naked pDNA soln. in balloon-injured rat carotid arteries resulted in significant expression. In conclusion, a facile method for embedding cationic formulations of pDNA in collagen matrixes was developed. These bioactive matrixes seem to be suitable for tissue engineering and local gene therapy strategies.
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41Rutsch, A.; Kantsjö, J. B.; Ronchi, F. The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. Front. Immunol. 2020, 11, 604179, DOI: 10.3389/fimmu.2020.60417941https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitVCnsL8%253D&md5=ae2dc7a2f0e92a3158a44011755e4cdcThe gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathologyRutsch, Andrina; Kantsjo, Johan B.; Ronchi, FrancescaFrontiers in Immunology (2020), 11 (), 604179CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. The human microbiota has a fundamental role in host physiol. and pathol. Gut microbial alteration, also known as dysbiosis, is a condition assocd. not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiol. and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gutbrain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and assocd. with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressivelike disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the prodn. of proinflammatory cytokines (interleukin-1b and interleukin-1β) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.
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42Drossman, D. A.; Hasler, W. L. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology 2016, 150, 1257– 1261, DOI: 10.1053/j.gastro.2016.03.03542https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28bmsFyhsQ%253D%253D&md5=27727046d3fb8623210eb13dcae74c85Rome IV-Functional GI Disorders: Disorders of Gut-Brain InteractionDrossman Douglas A; Hasler William LGastroenterology (2016), 150 (6), 1257-61 ISSN:.There is no expanded citation for this reference.
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43Perez-Muñoz, M. E.; Arrieta, M.-C.; Ramer-Tait, A. E.; Walter, J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 2017, 5, 48, DOI: 10.1186/s40168-017-0268-443https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1critlWquw%253D%253D&md5=ed193fdc5a2e0d6896d48b5d74a43cd7A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiomePerez-Munoz Maria Elisa; Walter Jens; Arrieta Marie-Claire; Arrieta Marie-Claire; Ramer-Tait Amanda E; Walter JensMicrobiome (2017), 5 (1), 48 ISSN:.After more than a century of active research, the notion that the human fetal environment is sterile and that the neonate's microbiome is acquired during and after birth was an accepted dogma. However, recent studies using molecular techniques suggest bacterial communities in the placenta, amniotic fluid, and meconium from healthy pregnancies. These findings have led many scientists to challenge the "sterile womb paradigm" and propose that microbiome acquisition instead begins in utero, an idea that would fundamentally change our understanding of gut microbiota acquisition and its role in human development. In this review, we provide a critical assessment of the evidence supporting these two opposing hypotheses, specifically as it relates to (i) anatomical, immunological, and physiological characteristics of the placenta and fetus; (ii) the research methods currently used to study microbial populations in the intrauterine environment; (iii) the fecal microbiome during the first days of life; and (iv) the generation of axenic animals and humans. Based on this analysis, we argue that the evidence in support of the "in utero colonization hypothesis" is extremely weak as it is founded almost entirely on studies that (i) used molecular approaches with an insufficient detection limit to study "low-biomass" microbial populations, (ii) lacked appropriate controls for contamination, and (iii) failed to provide evidence of bacterial viability. Most importantly, the ability to reliably derive axenic animals via cesarean sections strongly supports sterility of the fetal environment in mammals. We conclude that current scientific evidence does not support the existence of microbiomes within the healthy fetal milieu, which has implications for the development of clinical practices that prevent microbiome perturbations after birth and the establishment of future research priorities.
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44Dominguez-Bello, M. G.; Costello, E. K.; Contreras, M.; Magris, M.; Hidalgo, G.; Fierer, N.; Knight, R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 11971– 11975, DOI: 10.1073/pnas.100260110744https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cnlslKksg%253D%253D&md5=0aaa3ce83c3d727862accea6cbc2401aDelivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newbornsDominguez-Bello Maria G; Costello Elizabeth K; Contreras Monica; Magris Magda; Hidalgo Glida; Fierer Noah; Knight RobProceedings of the National Academy of Sciences of the United States of America (2010), 107 (26), 11971-5 ISSN:.Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.
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45Hill, C. J.; Lynch, D. B.; Murphy, K.; Ulaszewska, M.; Jeffery, I. B.; O’Shea, C. A.; Watkins, C.; Dempsey, E.; Mattivi, F.; Tuohy, K. Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome 2017, 5, 4, DOI: 10.1186/s40168-016-0213-y45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1c7msFykug%253D%253D&md5=37ab7baa46268117464df0482f93e01aEvolution of gut microbiota composition from birth to 24 weeks in the INFANTMET CohortHill Cian J; Lynch Denise B; Murphy Kiera; Jeffery Ian B; Ross R Paul; O' Toole Paul W; Hill Cian J; Lynch Denise B; Murphy Kiera; Ross R Paul; Ryan C Anthony; O' Toole Paul W; Stanton Catherine; Murphy Kiera; Watkins Claire; Stanton Catherine; Ulaszewska Marynka; Mattivi Fulvio; Tuohy Kieran; O'Shea Carol Anne; Dempsey Eugene; Ryan C AnthonyMicrobiome (2017), 5 (1), 4 ISSN:.BACKGROUND: The gut is the most extensively studied niche of the human microbiome. The aim of this study was to characterise the initial gut microbiota development of a cohort of breastfed infants (n = 192) from 1 to 24 weeks of age. METHODS: V4-V5 region 16S rRNA amplicon Illumina sequencing and, in parallel, bacteriological culture. The metabolomic profile of infant urine at 4 weeks of age was also examined by LC-MS. RESULTS: Full-term (FT), spontaneous vaginally delivered (SVD) infants' microbiota remained stable at both phylum and genus levels during the 24-week period examined. FT Caesarean section (CS) infants displayed an increased faecal abundance of Firmicutes (p < 0.01) and lower abundance of Actinobacteria (p < 0.001) after the first week of life compared to FT-SVD infants. FT-CS infants gradually progressed to harbouring a microbiota closely resembling FT-SVD (which remained stable) by week 8 of life, which was maintained at week 24. The gut microbiota of preterm (PT) infants displayed a significantly greater abundance of Proteobacteria compared to FT infants (p < 0.001) at week 1. Metabolomic analysis of urine at week 4 indicated PT-CS infants have a functionally different metabolite profile than FT (both CS and SVD) infants. Co-inertia analysis showed co-variation between the urine metabolome and the faecal microbiota of the infants. Tryptophan and tyrosine metabolic pathways, as well as fatty acid and bile acid metabolism, were found to be affected by delivery mode and gestational age. CONCLUSIONS: These findings confirm that mode of delivery and gestational age both have significant effects on early neonatal microbiota composition. There is also a significant difference between the metabolite profile of FT and PT infants. Prolonged breastfeeding was shown to have a significant effect on the microbiota composition of FT-CS infants at 24 weeks of age, but interestingly not on that of FT-SVD infants. Twins had more similar microbiota to one another than between two random infants, reflecting the influence of similarities in both host genetics and the environment on the microbiota..
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46Vatanen, T.; Jabbar, K. S.; Ruohtula, T.; Honkanen, J.; Avila-Pacheco, J.; Siljander, H.; Stražar, M.; Oikarinen, S.; Hyöty, H.; Ilonen, J. Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism. Cell 2022, 185, 4921– 4936.e4915, DOI: 10.1016/j.cell.2022.11.02346https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtFOktr7P&md5=1185b098b457b0ef3cfe3ea2f2d498c0Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolismVatanen, Tommi; Jabbar, Karolina S.; Ruohtula, Terhi; Honkanen, Jarno; Avila-Pacheco, Julian; Siljander, Heli; Strazar, Martin; Oikarinen, Sami; Hyoty, Heikki; Ilonen, Jorma; Mitchell, Caroline M.; Yassour, Moran; Virtanen, Suvi M.; Clish, Clary B.; Plichta, Damian R.; Vlamakis, Hera; Knip, Mikael; Xavier, Ramnik J.Cell (Cambridge, MA, United States) (2022), 185 (26), 4921-4936.e15CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The perinatal period represents a crit. window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 yr of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes assocd. with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite assocns. not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular-but not extensively hydrolyzed-formula were distinct from those of exclusively breastfed infants. Taken together, our integrative anal. expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life.
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47Baleato, C. L.; Ferguson, J. J. A.; Oldmeadow, C.; Mishra, G. D.; Garg, M. L. Plant-Based Dietary Patterns versus Meat Consumption and Prevalence of Impaired Glucose Intolerance and Diabetes Mellitus: A Cross-Sectional Study in Australian Women. Nutrients 2022, 14, 4152, DOI: 10.3390/nu1419415247https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xis1yltr%252FJ&md5=3ba139d4a14dc5178154790ac8c366b9Plant-Based Dietary Patterns versus Meat Consumption and Prevalence of Impaired Glucose Intolerance and Diabetes Mellitus: A Cross-Sectional Study in Australian WomenBaleato, Courtney L.; Ferguson, Jessica J. A.; Oldmeadow, Christopher; Mishra, Gita D.; Garg, Manohar L.Nutrients (2022), 14 (19), 4152CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)This study aimed to compare the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) among Australian women following plant-based diets (PBD) compared to regular meat eaters. A cross sectional anal. of the mid-aged cohort (1946-1951) of the Australian Longitudinal Study on Women's Health was conducted on completers of Survey 7 in 2013 with complete FFQ data available (n = 9102). Dietary patterns were categorized as PBD (vegan, lacto-ovo vegetarian, pesco-vegetarian, semi-vegetarian) and regular meat eaters. Meat eaters were further categorized into high and low consumption and outcomes included self-reported prevalence of IGT and DM. Participants were identified as regular meat eaters (n = 8937) and PBD (n = 175). Prevalence of IGT was lower in PBD (0-1.2%) compared to regular meat eaters (9.1%). Consolidation of PBD to a single group (vegetarians) indicated a lower prevalence of DM in vegetarians compared to regular meat eaters (3.9% vs. 9.1%). Women consuming meat daily/multiple times per day had significantly higher odds of IGT (OR 1.5, 95%CI 1.1 to 2.1, p = 0.02). Individuals consuming processed meat daily/multiple times per day had significantly higher odds of DM compared to those consuming less than daily (Odds ratio (OR) 1.7, 95% confidence interval (CI) 1.3 to 2.3, p < 0.0001). After adjustment for covariates, statistical significance was lost largely due to the addn. of BMI to the model. Prevalence of IGT and DM were lower in women following PBD and higher in high consumers of meat and processed meat. The relationship between meat consumption and IGT/diabetes status appears to be mediated, at least in part, by an increase in body mass index (BMI). Future studies are warranted to investigate the mechanisms and other lifestyle factors underpinning the assocn. between high meat consumption and increased risk of IGT and DM.
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48Keaver, L.; Ruan, M.; Chen, F.; Du, M.; Ding, C.; Wang, J.; Shan, Z.; Liu, J.; Zhang, F. F. Plant- and animal-based diet quality and mortality among US adults: a cohort study. Br. J. Nutr. 2021, 125, 1405– 1415, DOI: 10.1017/S000711452000367048https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtFaisLbF&md5=8f55f34569e6b7dd7575a1a841dffd7dPlant- and animal-based diet quality and mortality among US adults: a cohort studyKeaver, Laura; Ruan, Mengyuan; Chen, Fan; Du, Mengxi; Ding, Chenyueyi; Wang, Jiaqi; Shan, Zhilei; Liu, Junxiu; Zhang, Fang FangBritish Journal of Nutrition (2021), 125 (12), 1405-1415CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)Not all plant-based and animal foods exert the same health effects due to their various nutrient compns. We aimed to assess the quality of plant-based v. animal foods in relation to mortality in a prospective cohort study. Using data collected from a nationally representative sample of 36 825 adults in the National Health and Nutrition Examn. Survey 1999-2014, we developed a de novo Comprehensive Diet Quality Index (cDQI) that assesses the quality of seventeen foods based on the healthfulness and sep. scored the quality of eleven plant-based foods in a plant-based Diet Quality Index (pDQI) and six animal foods in an animal-based Diet Quality Index (aDQI). Mortality from all causes, heart disease and cancer were obtained from linkage to the National Death Index up to 31 Dec. 2015. Cox proportional hazard models were used to est. hazard ratios (HR) and 95 % CI after multivariable adjustments. During a median follow-up of 8·3 years, 4669 all-cause deaths occurred, including 798 deaths due to heart disease and 1021 due to cancer. Compared with individuals in the lowest quartile, those in the highest quartile of cDQI had a lower risk of all-cause mortality (HR 0·75, 95 % CI 0·65, 0·86; P trend < 0·001), which largely reflected the inverse relationship between quality of plant-based foods (pDQI) and all-cause mortality (HR 0·66, 95 % CI 0·58, 0·74; P trend < 0·001). No independent assocn. was found for the quality of animal foods (aDQI) and mortality. Our results suggest that consuming healthy plant-based foods is assocd. with lower all-cause mortality among US adults.
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49O’Mahony, S. M.; Marchesi, J. R.; Scully, P.; Codling, C.; Ceolho, A.-M.; Quigley, E. M. M.; Cryan, J. F.; Dinan, T. G. Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses. Biol. Psychiatry 2009, 65, 263– 267, DOI: 10.1016/j.biopsych.2008.06.02649https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M%252FntlSrug%253D%253D&md5=5fc242a46520953c886d1a25e854f9a0Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnessesO'Mahony Siobhain M; Marchesi Julian R; Scully Paul; Codling Caroline; Ceolho Anne-Marie; Quigley Eamonn M M; Cryan John F; Dinan Timothy GBiological psychiatry (2009), 65 (3), 263-7 ISSN:.BACKGROUND: Adverse early life events are associated with a maladaptive stress response system and might increase the vulnerability to disease in later life. Several disorders have been associated with early life stress, ranging from depression to irritable bowel syndrome. This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable. METHODS: The purpose of this study was to assess the effect of early life stress on the brain-gut axis. Male rat pups were stressed by separating them from their mothers for 3 hours daily between postnatal days 2-12. The control group was left undisturbed with their mothers. Behavior, immune response, stress sensitivity, visceral sensation, and fecal microbiota were analyzed. RESULTS: The early life stress increased the number of fecal boli in response to a novel stress. Plasma corticosterone was increased in the maternally separated animals. An increase in the systemic immune response was noted in the stressed animals after an in vitro lipopolysaccharide challenge. Increased visceral sensation was seen in the stressed group. There was an alteration of the fecal microbiota when compared with the control group. CONCLUSIONS: These results show that this form of early life stress results in an altered brain-gut axis and is therefore an important model for investigating potential mechanistic insights into stress-related disorders including depression and IBS.
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50Jernberg, C.; Löfmark, S.; Edlund, C.; Jansson, J. K. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology (Reading) 2010, 156, 3216– 3223, DOI: 10.1099/mic.0.040618-050https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsFCiur3F&md5=56649fa26b86128690cb19944423b1adLong-term impacts of antibiotic exposure on the human intestinal microbiotaJernberg, Cecilia; Loefmark, Sonja; Edlund, Charlotta; Jansson, Janet K.Microbiology (Reading, United Kingdom) (2010), 156 (11), 3216-3223CODEN: MROBEO; ISSN:1350-0872. (Society for General Microbiology)A review. Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that the impacts of some antibiotics remain for extended periods of time. In addn., antibiotic-resistant strains can persist in the human host environment in the absence of selective pressure. Both mol.- and cultivation-based approaches have revealed ecol. disturbances in the microbiota after antibiotic administration, in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question. A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic-resistant pathogenic strains.
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51Caporaso, J. G.; Kuczynski, J.; Stombaugh, J.; Bittinger, K.; Bushman, F. D.; Costello, E. K.; Fierer, N.; Peña, A. G.; Goodrich, J. K.; Gordon, J. I. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods 2010, 7, 335– 336, DOI: 10.1038/nmeth.f.30351https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXksFalurg%253D&md5=0f3e337921b1cc48bc697f0ee92bf5b8QIIME allows analysis of high-throughput community sequencing dataCaporaso, J. Gregory; Kuczynski, Justin; Stombaugh, Jesse; Bittinger, Kyle; Bushman, Frederic D.; Costello, Elizabeth K.; Fierer, Noah; Pena, Antonio Gonzalez; Goodrich, Julia K.; Gordon, Jeffrey I.; Huttley, Gavin A.; Kelley, Scott T.; Knights, Dan; Koenig, Jeremy E.; Ley, Ruth E.; Lozupone, Catherine A.; McDonald, Daniel; Muegge, Brian D.; Pirrung, Meg; Reeder, Jens; Sevinsky, Joel R.; Turnbaugh, Peter J.; Walters, William A.; Widmann, Jeremy; Yatsunenko, Tanya; Zaneveld, Jesse; Knight, RobNature Methods (2010), 7 (5), 335-336CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)There is no expanded citation for this reference.
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52Tang, L. Sequence-based identification of human-associated microbiota. https://www.nature.com/articles/d42859-019-00011-5 (accessed October 24, 2022).There is no corresponding record for this reference.
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53Collins, S. M.; Surette, M.; Bercik, P. The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 2012, 10, 735– 742, DOI: 10.1038/nrmicro287653https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhtlylt7%252FJ&md5=097611d85e63be4c96cb92f83be0367dThe interplay between the intestinal microbiota and the brainCollins, Stephen M.; Surette, Michael; Bercik, PremyslNature Reviews Microbiology (2012), 10 (11), 735-742CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)A review. The intestinal microbiota consists of a vast bacterial community that resides primarily in the lower gut and lives in a symbiotic relationship with the host. A bidirectional neurohumoral communication system, known as the gut-brain axis, integrates the host gut and brain activities. Here, we describe the recent advances in our understanding of how the intestinal microbiota communicates with the brain via this axis to influence brain development and behavior. We also review how this extended communication system might influence a broad spectrum of diseases, including irritable bowel syndrome, psychiatric disorders and demyelinating conditions such as multiple sclerosis.
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54Lagier, J.-C.; Armougom, F.; Million, M.; Hugon, P.; Pagnier, I.; Robert, C.; Bittar, F.; Fournous, G.; Gimenez, G.; Maraninchi, M. Microbial culturomics: paradigm shift in the human gut microbiome study. Clinical Microbiology and Infection 2012, 18, 1185– 1193, DOI: 10.1111/1469-0691.1202354https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1Gru7bP&md5=e7f57683de2adea0585015247a6dd5feMicrobial culturomics: paradigm shift in the human gut microbiome studyLagier, J.-C.; Armougom, F.; Million, M.; Hugon, P.; Pagnier, I.; Robert, C.; Bittar, F.; Fournous, G.; Gimenez, G.; Maraninchi, M.; Trape, J.-F.; Koonin, E. V.; La Scola, B.; Raoult, D.Clinical Microbiology and Infection (2012), 18 (12), 1185-1193CODEN: CMINFM; ISSN:1198-743X. (Wiley-Blackwell)Abstr. : Comprehensive detn. of the microbial compn. of the gut microbiota and the relationships with health and disease are major challenges in the 21st century. Metagenomic anal. of the human gut microbiota detects mostly uncultured bacteria. We studied stools from two lean Africans and one obese European, using 212 different culture conditions (microbial culturomics), and tested the colonies by using mass spectrometry and 16S rRNA amplification and sequencing. In parallel, we analyzed the same three samples by pyrosequencing 16S rRNA amplicons targeting the V6 region. The 32 500 colonies obtained by culturomics have yielded 340 species of bacteria from seven phyla and 117 genera, including two species from rare phyla (Deinococcus-Thermus and Synergistetes), five fungi, and a giant virus (Senegalvirus). The microbiome identified by culturomics included 174 species never described previously in the human gut, including 31 new species and genera for which the genomes were sequenced, generating c. 10 000 new unknown genes (ORFans), which will help in future mol. studies. Among these, the new species Microvirga massiliensis has the largest bacterial genome so far obtained from a human, and Senegalvirus is the largest virus reported in the human gut. Concurrent metagenomic anal. of the same samples produced 698 phylotypes, including 282 known species, 51 of which overlapped with the microbiome identified by culturomics. Thus, culturomics complements metagenomics by overcoming the depth bias inherent in metagenomic approaches.
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55Smith, P. M.; Howitt, M. R.; Panikov, N.; Michaud, M.; Gallini, C. A.; Bohlooly, Y. M.; Glickman, J. N.; Garrett, W. S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013, 341, 569– 573, DOI: 10.1126/science.124116555https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFyjsr3P&md5=8d7d91434f35758f764d89ab48527cacThe Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell HomeostasisSmith, Patrick M.; Howitt, Michael R.; Panikov, Nicolai; Michaud, Monia; Gallini, Carey Ann; Bohlooly-Y, Mohammad; Glickman, Jonathan N.; Garrett, Wendy S.Science (Washington, DC, United States) (2013), 341 (6145), 569-573CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Regulatory T cells (Tregs) that express the transcription factor Foxp3 are crit. for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific mols. that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, the authors posited that more prevalent factors exist that regulate the no. and function of colonic Tregs. The authors detd. that short-chain fatty acids, gut microbiota-derived bacterial fermn. products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. This study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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56Atarashi, K.; Tanoue, T.; Oshima, K.; Suda, W.; Nagano, Y.; Nishikawa, H.; Fukuda, S.; Saito, T.; Narushima, S.; Hase, K. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013, 500, 232– 236, DOI: 10.1038/nature1233156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFShsbfJ&md5=ae3e310120459e75a80926aca55d4f2fTreg induction by a rationally selected mixture of Clostridia strains from the human microbiotaAtarashi, Koji; Tanoue, Takeshi; Oshima, Kenshiro; Suda, Wataru; Nagano, Yuji; Nishikawa, Hiroyoshi; Fukuda, Shinji; Saito, Takuro; Narushima, Seiko; Hase, Koji; Kim, Sangwan; Fritz, Joelle V.; Wilmes, Paul; Ueha, Satoshi; Matsushima, Kouji; Ohno, Hiroshi; Olle, Bernat; Sakaguchi, Shimon; Taniguchi, Tadatsugu; Morita, Hidetoshi; Hattori, Masahira; Honda, KenyaNature (London, United Kingdom) (2013), 500 (7461), 232-236CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases. Although numerous probiotic microorganisms have been identified, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiol. manner. Here the authors use a rational approach to isolate CD4+FOXP3+ regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human fecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in Treg-cell-inducing species. From these mice, the authors isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing Treg cell abundance and inducing important anti-inflammatory mols.-including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS)-in Treg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-β-rich environment to help expansion and differentiation of Treg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders.
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57Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J. R.; Pfeffer, K.; Coffer, P. J. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013, 504, 451– 455, DOI: 10.1038/nature1272657https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOmtrrJ&md5=5df9a8c09b9b0e7f98522dfe16ef2711Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generationArpaia, Nicholas; Campbell, Clarissa; Fan, Xiying; Dikiy, Stanislav; van der Veeken, Joris; de Roos, Paul; Liu, Hui; Cross, Justin R.; Pfeffer, Klaus; Coffer, Paul J.; Rudensky, Alexander Y.Nature (London, United Kingdom) (2013), 504 (7480), 451-455CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the compn. of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the mol. cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, the authors reasoned that their metabolic byproducts are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. The authors tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. The authors found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermn., facilitated extrathymic generation of Treg cells. A boost in Treg-cell nos. after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the obsd. phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addn. to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. The results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
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58Donia, M. S.; Cimermancic, P.; Schulze, C. J.; Wieland Brown, L. C.; Martin, J.; Mitreva, M.; Clardy, J.; Linington, R. G.; Fischbach, M. A. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 2014, 158, 1402– 1414, DOI: 10.1016/j.cell.2014.08.03258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFCgtLvP&md5=2588272748281d6e3f18966e2c74a702A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibioticsDonia, Mohamed S.; Cimermancic, Peter; Schulze, Christopher J.; Wieland Brown, Laura C.; Martin, John; Mitreva, Makedonka; Clardy, Jon; Linington, Roger G.; Fischbach, Michael A.Cell (Cambridge, MA, United States) (2014), 158 (6), 1402-1414CODEN: CELLB5; ISSN:0092-8674. (Cell Press)In complex biol. systems, small mols. often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, the authors identified 3118 small-mol. biosynthetic gene clusters (BGCs) in genomes of human-assocd. bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, they discovered that BGCs for a class of antibiotics in clin. trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. The authors purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. They demonstrated that lactocillin has potent antibacterial activity against a range of Gram-pos. vaginal pathogens, and they showed that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. These findings illustrate the widespread distribution of small-mol.-encoding BGCs in the human microbiome, and they demonstrate the bacterial prodn. of drug-like mols. in humans.
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59Lurie, I.; Yang, Y. X.; Haynes, K.; Mamtani, R.; Boursi, B. Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study. J. Clin. Psychiatry 2015, 76, 1522– 1528, DOI: 10.4088/JCP.15m0996159https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28visl2isg%253D%253D&md5=2d27297be935450c1c6fd82b0c0d25deAntibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control studyLurie Ido; Lurie Ido; Yang Yu-Xiao; Haynes Kevin; Mamtani Ronac; Boursi BenThe Journal of clinical psychiatry (2015), 76 (11), 1522-8 ISSN:.OBJECTIVE: Changes in the microbiota (dysbiosis) were suggested to increase the risk of several psychiatric conditions through neurologic, metabolic, and immunologic pathways. Our aim was to assess whether exposure to specific antibiotic groups increases the risk for depression, anxiety, or psychosis. METHOD: We conducted 3 nested case-control studies during the years 1995-2013 using a large population-based medical record database from the United Kingdom. The study included 202,974 patients with depression, 14,570 with anxiety, and 2,690 with psychosis and 803,961, 57,862, and 10,644 matched controls, respectively. Cases were defined as individuals aged 15-65 years with any medical Read code for depression, anxiety, or psychosis. Subjects with diagnosis-specific psychotropic prescriptions > 90 days before index date were excluded. For every case, 4 controls were selected using incidence density sampling, matching on age, sex, practice site, calendar time, and duration of follow-up before index date. The primary exposure of interest was therapy with 1 of 7 antibiotic classes > 1 year before index date. Odds ratios (ORs) and 95% CIs were calculated for the association between each psychiatric disorder and exposure to individual classes of antibiotics using conditional logistic regression analysis. The risk was adjusted for obesity, smoking history, alcohol consumption, socioeconomic status, and number of infectious events before diagnosis. RESULTS: Treatment with a single antibiotic course was associated with higher risk for depression with all antibiotic groups, with an adjusted OR (AOR) of 1.23 for penicillins (95% CI, 1.18-1.29) and 1.25 (95% CI, 1.15-1.35) for quinolones. The risk increased with recurrent antibiotic exposures to 1.40 (95% CI, 1.35-1.46) and 1.56 (95% CI, 1.46-1.65) for 2-5 and > 5 courses of penicillin, respectively. Similar association was observed for anxiety and was most prominent with exposures to penicillins and sulfonamides, with an AOR of 1.17 (95% CI, 1.01-1.36) for a single course of penicillin and 1.44 (95% CI, 1.18-1.75) for > 5 courses. There was no change in risk for psychosis with any antibiotic group. There was a mild increase in the risk of depression and anxiety with a single course of antifungals; however, there was no increase in risk with repeated exposures. CONCLUSION: Recurrent antibiotic exposure is associated with increased risk for depression and anxiety but not for psychosis.
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60Zheng, P.; Zeng, B.; Zhou, C.; Liu, M.; Fang, Z.; Xu, X.; Zeng, L.; Chen, J.; Fan, S.; Du, X. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol. Psychiatry 2016, 21, 786– 796, DOI: 10.1038/mp.2016.4460https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmsVals78%253D&md5=58e19b9beef57cc353c806891f3ef2f0Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolismZheng, P.; Zeng, B.; Zhou, C.; Liu, M.; Fang, Z.; Xu, X.; Zeng, L.; Chen, J.; Fan, S.; Du, X.; Zhang, X.; Yang, D.; Yang, Y.; Meng, H.; Li, W.; Melgiri, N. D.; Licinio, J.; Wei, H.; Xie, P.Molecular Psychiatry (2016), 21 (6), 786-796CODEN: MOPSFQ; ISSN:1359-4184. (Nature Publishing Group)Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiol. of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clin. sampling, the gut microbiotic compns. of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metab. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metab.
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61Davis, D. J.; Hecht, P. M.; Jasarevic, E.; Beversdorf, D. Q.; Will, M. J.; Fritsche, K.; Gillespie, C. H. Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice. Brain, Behavior, and Immunity 2017, 59, 38– 48, DOI: 10.1016/j.bbi.2016.09.00361https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsV2hu7bF&md5=f827c7e72227a384d1ab9d225bc3b2beSex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated miceDavis, Daniel J.; Hecht, Patrick M.; Jasarevic, Eldin; Beversdorf, David Q.; Will, Matthew J.; Fritsche, Kevin; Gillespie, Catherine H.Brain, Behavior, and Immunity (2017), 59 (), 38-48CODEN: BBIMEW; ISSN:0889-1591. (Elsevier)Dietary supplementation with the long-chain omega-3 polyunsatd. fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms assocd. with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a crit. role in regulating various biol. processes in the brain and may contribute to neuropsychiatric disease risk. The present study detd. the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28 days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24 h and 7 days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were obsd. in female mice. As the microbiota-brain-axis has been recently implicated in behavior, compn. of microbial communities were analyzed to examine if these sex-specific effects of DHA may be assocd. with changes in the gut microbiota (GM). Clear sex differences were obsd. with males and females showing distinct microbial compns. prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes obsd. in the male mice. Predictive metagenome anal. using PICRUSt was performed on the fecal samples collected from males and identified enrichment in functional KEGG pathway terms relevant to processes such as the biosynthesis of unsatd. fatty acids and antioxidant metab. These results indicate that DHA alters commensal community compn. and produces beneficial effects on anxiety and depressive-like behaviors in a sex-specific manner. The present study provides insight into the mechanistic role that gut microbes may play in the regulation of anxiety and depressive-like behaviors and how dietary intervention can modulate these effects.
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62Pasolli, E.; Asnicar, F.; Manara, S.; Zolfo, M.; Karcher, N.; Armanini, F.; Beghini, F.; Manghi, P.; Tett, A.; Ghensi, P. Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle. Cell 2019, 176, 649– 662.e20, DOI: 10.1016/j.cell.2019.01.00162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsVars7w%253D&md5=28875385d40b31967e02ad1538cf2c57Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and LifestylePasolli, Edoardo; Asnicar, Francesco; Manara, Serena; Zolfo, Moreno; Karcher, Nicolai; Armanini, Federica; Beghini, Francesco; Manghi, Paolo; Tett, Adrian; Ghensi, Paolo; Collado, Maria Carmen; Rice, Benjamin L.; DuLong, Casey; Morgan, Xochitl C.; Golden, Christopher D.; Quince, Christopher; Huttenhower, Curtis; Segata, NicolaCell (Cambridge, MA, United States) (2019), 176 (3), 649-662.e20CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many assocd. with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the av. mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-assocd. microbes, and allow better exploitation of metagenomic technologies.
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63Nayfach, S.; Shi, Z. J.; Seshadri, R.; Pollard, K. S.; Kyrpides, N. C. New insights from uncultivated genomes of the global human gut microbiome. Nature 2019, 568, 505– 510, DOI: 10.1038/s41586-019-1058-x63https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXosVSgsbo%253D&md5=3a9d99af65b1dfad3b0e591fa19c8e16New insights from uncultivated genomes of the global human gut microbiomeNayfach, Stephen; Shi, Zhou Jason; Seshadri, Rekha; Pollard, Katherine S.; Kyrpides, Nikos C.Nature (London, United Kingdom) (2019), 568 (7753), 505-510CODEN: NATUAS; ISSN:0028-0836. (Nature Research)The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under lab. conditions. We address this problem by reconstructing 60,664 draft prokaryotic genomes from 3810 fecal metagenomes, from geog. and phenotypically diverse humans. These genomes provide ref. points for 2058 newly identified species-level operational taxonomic units (OTUs), which represents a 50% increase over the previously known phylogenetic diversity of sequenced gut bacteria. On av., the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual, and are enriched in humans from rural populations. A meta-anal. of clin. gut-microbiome studies pinpointed numerous disease assocns. for the newly identified OTUs, which have the potential to improve predictive models. Finally, our anal. revealed that uncultured gut species have undergone genome redn. that has resulted in the loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.
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64Pusceddu, M. M.; Barboza, M.; Schneider, M.; Stokes, P.; Sladek, J. A.; Torres-Fuentes, C.; Goldfild, L. R.; Gillis, S. E.; Brust-Mascher, I.; Rabasa, G. Nod-like receptors are critical for gut-brain axis signaling in mice. J. Physiol. 2019, 597, 5777– 5797, DOI: 10.1113/JP27864064https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1arurzK&md5=a061ded6626d4888d224db082722f1d2Nod-like receptors are critical for gut-brain axis signalling in micePusceddu, Matteo M.; Barboza, Mariana; Keogh, Ciara E.; Schneider, Melinda; Stokes, Patricia; Sladek, Jessica A.; Kim, Hyun Jung D.; Torres-Fuentes, Cristina; Goldfild, Lily R.; Gillis, Shane E.; Brust-Mascher, Ingrid; Rabasa, Gonzalo; Wong, Kyle A.; Lebrilla, Carlito; Byndloss, Mariana X.; Maisonneuve, Charles; Baeumler, Andreas J.; Philpott, Dana J.; Ferrero, Richard L.; Barrett, Kim E.; Reardon, Colin; Gareau, Melanie G.Journal of Physiology (Oxford, United Kingdom) (2019), 597 (24), 5777-5797CODEN: JPHYA7; ISSN:1469-7793. (Wiley-Blackwell)Key points : ·Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. ·Nod-like receptors regulate central and peripheral serotonergic biol. ·Nod-like receptors are important for maintenance of gastrointestinal physiol. ·Intestinal epithelial cell expression of Nod1 receptors regulate behavior. Gut-brain axis signalling is crit. for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiol. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addn., NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress.
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65Pellegrini, C.; Antonioli, L.; Calderone, V.; Colucci, R.; Fornai, M.; Blandizzi, C. Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?. Prog. Neurobiol. 2020, 191, 101806, DOI: 10.1016/j.pneurobio.2020.10180665https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVClsrrN&md5=81eaecf674dc6963a355a67b47845bb0Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communicationsPellegrini, Carolina; Antonioli, Luca; Calderone, Vincenzo; Colucci, Rocchina; Fornai, Matteo; Blandizzi, CorradoProgress in Neurobiology (Oxford, United Kingdom) (2020), 191 (), 101806CODEN: PGNBA5; ISSN:0301-0082. (Elsevier Ltd.)A review. Growing evidence highlights the relevance of microbiota-gut-brain axis in the maintenance of brain homeostasis as well as in the pathophysiol. of major neurol. and psychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD) and major depressive disorder (MDD). Of note, the nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-contg. protein 3 (NLRP3) inflammasome acts as a key player in both coordinating the host physiol. and shaping the peripheral and central immune/inflammatory responses in CNS diseases. The present review provides an overview of current knowledge on the role of microbiota-gut-inflammasome-brain axis in the major CNS diseases, including PD, AD, MS, ASD and MDD. In particular, though no direct and causal correlation among altered gut microbiota, NLRP3 activation and brain pathol. has been demonstrated and in-depth studies are needed in this setting, our purpose was to pave the way to a novel and pioneering perspective on the pathophysiol. of CNS disorders. Our intent was also to highlight and discuss whether alterations of microbiota-gut-inflammasome-brain axis support a holistic view of the pathophysiol. of CNS diseases, even though each disorder displays a different clin. picture.
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66Zhao, K.; Yao, M.; Zhang, X.; Xu, F.; Shao, X.; Wei, Y.; Wang, H. Flavonoids and intestinal microbes interact to alleviate depression. Journal of the Science of Food and Agriculture 2022, 102, 1311– 1318, DOI: 10.1002/jsfa.1157866https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlCntbvF&md5=53b83d6529ef0b11cacf7b6b687c9fbbFlavonoids and intestinal microbes interact to alleviate depressionZhao, Ke; Yao, Mei; Zhang, Xin; Xu, Feng; Shao, Xingfeng; Wei, Yingying; Wang, HongfeiJournal of the Science of Food and Agriculture (2022), 102 (4), 1311-1318CODEN: JSFAAE; ISSN:0022-5142. (John Wiley & Sons Ltd.)A review. Flavonoids have a variety of biol. activities that are beneficial to human health. However, owing to low bioavailability, most flavonoids exert beneficial effects in the intestine through metab. by the flora into a variety of structurally different derivs. Also, flavonoids can modulate the type and structure of intestinal microorganisms to improve human health. It has been reported that the development of depression is accompanied by changes in the type and no. of intestinal microorganisms, and gut microbes can significantly improve depressive symptoms through the gut-brain axis. Therefore, the interaction between flavonoids and intestinal microbes to alleviate depression is discussed.
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67Segre, J. A. What does it take to satisfy Koch’s postulates two centuries later? Microbial genomics and Propionibacteria acnes. J. Invest. Dermatol. 2013, 133, 2141– 2142, DOI: 10.1038/jid.2013.26067https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVykur%252FP&md5=165251fa065804d5cdc60736bf7e939eWhat Does It Take to Satisfy Koch's Postulates Two Centuries Later?: Microbial Genomics and Propionibacteria acnesSegre, Julia A.Journal of Investigative Dermatology (2013), 133 (9), 2141-2142CODEN: JIDEAE; ISSN:0022-202X. (Nature Publishing Group)For two centuries, Koch's postulates have set the gold std. for establishing the microbiol. etiol. of infection and disease. Genomic sequencing now brings finer resoln. to both bacterial strain variation and the host genetic state that may predispose to disease. In this issue of the JID, Fitz-Gibbons and colleagues present strain-based resoln. of Propionibacterium acnes and its assocn. with the common teenage malady acne vulgaris. Here I examine how Koch's postulates were envisioned and incorporate this finer resoln. of both host and microbial states.
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68Eiseman, B.; Silen, W.; Bascom, G. S.; Kauvar, A. J. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958, 44, 854– 85968https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaG1M%252Fit1ShtA%253D%253D&md5=932cb97103c858a9f7c3112e2e61dca1Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitisEISEMAN B; SILEN W; BASCOM G S; KAUVAR A JSurgery (1958), 44 (5), 854-9 ISSN:0039-6060.There is no expanded citation for this reference.
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69Reyniers, J. A. The pure-culture concept and gnotobiotics. Ann. N.Y. Acad. Sci. 1959, 78, 3– 16, DOI: 10.1111/j.1749-6632.1959.tb53091.xThere is no corresponding record for this reference.
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70Schaedler, R. W.; Dubos, R.; Costello, R. ASSOCIATION OF GERMFREE MICE WITH BACTERIA ISOLATED FROM NORMAL MICE. J. Exp. Med. 1965, 122, 77– 82, DOI: 10.1084/jem.122.1.7770https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaF2M7jtVWmsQ%253D%253D&md5=c693bd4d999907652054e8ac1c18c68cASSOCIATION OF GERMFREE MICE WITH BACTERIA ISOLATED FROM NORMAL MICESCHAEDLER R W; DUBS R; COSTELLO RThe Journal of experimental medicine (1965), 122 (), 77-82 ISSN:0022-1007.Germfree mice were given food contaminated with pure cultures of various bacterial species isolated from ordinary healthy mice. The cultures were given singly, or in association, or consecutively at weekly intervals. Whatever the technique of administration, the lactobacilli and anaerobic streptococci immediately established themselves throughout the gastrointestinal tract, and became closely associated with the walls of the organs. In contrast, the organisms of the bacteroides group were found in large numbers only in the large intestine. Within a week after exposure, the populations of these three bacterial species reached levels similar to those found in ordinary mice. They remained at these characteristic levels throughout the period of observation (several months). Their presence resulted in a progressive decrease in the size of the cecum which eventually became normal in gross appearance. Coliform bacilli multiplied extensively and persisted at high levels in all parts of the gastrointestinal tract of germfree mice, even after these had become colonized with lactobacilli, anaerobic streptococci and bacteroides. However, the coliform population fell precipitously within a few days after the animals were fed the intestinal contents of healthy pathogen-free mice.
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71Peppercorn, M. A.; Goldman, P. The Role of Intestinal Bacteria in the Metabolism of Salicylazosulfapyridine. Journal of Pharmacology and Experimental Therapeutics 1972, 181, 555– 56271https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE38Xks12qt7c%253D&md5=149105b21c094828504bc77d66df2b80Role of intestinal bacteria in the metabolism of salicylazosulfapyridinePeppercorn, Mark A.; Goldman, PeterJournal of Pharmacology and Experimental Therapeutics (1972), 181 (3), 555-62CODEN: JPETAB; ISSN:0022-3565.Following oral administration of salicylazosulfapyridine (I) [599-79-1] to normal rats, sulfapyridine [144-83-2], 5-aminosalicylate [89-57-6], and their N-acetyl derivs. were found in the excreta. No unchanged I was found. Pretreatment of the rats with neomycin [1404-04-2] in order to decrease intestinal microflora resulted in fecal recovery of >50% of the administered dose of I as unchanged I. Intestinal bacteria appear responsible for the initial reaction in I biotransformation and this raises questions concerning the amt. of unchanged I that reaches the presumed site of action in inflammatory disease of the lower intestine.
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72Stark, P. L.; Lee, A. The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. J. Med. Microbiol. 1982, 15, 189– 203, DOI: 10.1099/00222615-15-2-18972https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL3s%252FlvFGqtw%253D%253D&md5=4c3b7442ffffe9234aebbad8912d627dThe microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of lifeStark P L; Lee AJournal of medical microbiology (1982), 15 (2), 189-203 ISSN:0022-2615.The succession of bacterial populations in the large bowel of seven breast-fed and seven formula-fed infants was examined during the first year of life. The composition of the intestinal microflora varied according to the infant's diet. During the first week of life breast-fed and formula-fed infants were colonised by enterobacteria and enterococci followed by bifidobacteria, Bacteroides spp., clostridia and anaerobic streptococci. From week 4 until solid foods were given, breast-fed babies had a simple flora consisting of bifidobacteria and relatively few enterobacteria and enterococci. Formula-fed babies during the corresponding period were more often colonised by other anaerobes in addition to bifidobacteria and had higher counts of facultatively anaerobic bacteria. The introduction of solid food to the breast-fed infants caused a major disturbance in the microbial ecology of the large bowel as counts of enterobacteria and enterococci rose sharply and colonisation by Bacteroides spp., clostridia and anaerobic streptococci occurred. This was not observed when formula-fed infants began to take solids; instead, counts of facultative anaerobes remained high while colonisation by anaerobes other than bifidobacteria continued. At 12 months, the anaerobic bacterial populations of the large bowel of breast-fed and formula-fed infants were beginning to resemble those of adults in number and composition and there was a corresponding decrease in the number of facultative anaerobes. These changes are discussed in relation to changes in susceptibility to gastro-intestinal infection.
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73Fleischmann, R. D.; Adams, M. D.; White, O.; Clayton, R. A.; Kirkness, E. F.; Kerlavage, A. R.; Bult, C. J.; Tomb, J. F.; Dougherty, B. A.; Merrick, J. M. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995, 269, 496– 512, DOI: 10.1126/science.754280073https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXntF2ksLc%253D&md5=471dc5b1db156773d4883e41b78ece77Whole-genome random sequencing and assembly of Haemophilus influenzae RdFleischmann, Robert D.; Adams, Mark D.; White, Owen; Clayton, Rebecca A.; Kirkness, Ewen F.; Kerlavage, Anthony R.; Bult, Carol J.; Tomb, Jean-Francois; Dougherty, Brian A.; et al.Science (Washington, D. C.) (1995), 269 (5223), 496-8, 507-12CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)An approach for genome anal. based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genomes maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession no. L42023) represents the only complete genome sequence from a free-living organism.
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74Wilson, K. H.; Blitchington, R. B. Human colonic biota studied by ribosomal DNA sequence analysis. Appl. Environ. Microbiol. 1996, 62, 2273– 2278, DOI: 10.1128/aem.62.7.2273-2278.199674https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XjvFGntro%253D&md5=a29cae5d95717df891d1b69cd23dcf93Human colonic biota studied by ribosomal DNA sequence analysisWilson, Kenneth H.; Blitchington, Rhonda B.Applied and Environmental Microbiology (1996), 62 (7), 2273-2278CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)Human colonic biota is a complex microbial ecosystem that serves as a host defense. Unlike most microbial ecosystems, its compn. has been studied extensively by relatively efficient culture methods. The authors have compared an established culture-based method with direct amplification and partial sequencing of cloned 16S rRNA genes from a human fecal specimen. Nine cycles of PCR were also compared with 35 cycles. Colonies and cloned amplicons were classified by comparing their ribosomal DNA (rDNA; DNA coding for rRNA) sequences with rDNA sequences of known phylogeny. Quant. culture recovered 58% of the microscopic count. The 48 colonies identified gave 21 rDNA sequences; it was estd. that 72% of the rDNA sequences from the total population of culturable cells would match these 21 sampled sequences (72% coverage). Fifty 9-cycle clones gave 27 sequences and 59% coverage of cloned rDNAs. Thirty-nine rDNAs cloned after 35 cycles of PCR gave 13 sequences for 74% coverage. Thus, the representation of the ecosystem after 35 cycles of PCR was distorted and lacked diversity. However, when the no. of temp. cycles was minimized, biodiversity was preserved, and there was good agreement between culturing bacteria and sampling rDNA directly.
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75Guarner, F.; Malagelada, J. R. Gut flora in health and disease. Lancet 2003, 361, 512– 519, DOI: 10.1016/S0140-6736(03)12489-075https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3s%252FntlKltg%253D%253D&md5=fd95e325ed4ca919a4d28659eb506038Gut flora in health and diseaseGuarner Francisco; Malagelada Juan-RLancet (London, England) (2003), 361 (9356), 512-9 ISSN:0140-6736.The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.
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76Rakoff-Nahoum, S.; Paglino, J.; Eslami-Varzaneh, F.; Edberg, S.; Medzhitov, R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004, 118, 229– 241, DOI: 10.1016/j.cell.2004.07.00276https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtlKntrg%253D&md5=08ed04f1969160743c82bae2b70a201bRecognition of commensal microflora by Toll-like receptors is required for intestinal homeostasisRakoff-Nahoum, Seth; Paglino, Justin; Eslami-Varzaneh, Fatima; Edberg, Stephen; Medzhitov, RuslanCell (Cambridge, MA, United States) (2004), 118 (2), 229-241CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is crit. for the protection against gut injury and assocd. mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
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77Mazmanian, S. K.; Liu, C. H.; Tzianabos, A. O.; Kasper, D. L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 2005, 122, 107– 118, DOI: 10.1016/j.cell.2005.05.00777https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmsFeiurw%253D&md5=029fa2f2e90305138740c220055e4f15An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune systemMazmanian, Sarkis K.; Liu, Cui Hua; Tzianabos, Arthur O.; Kasper, Dennis L.Cell (Cambridge, MA, United States) (2005), 122 (1), 107-118CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial mols. mediating symbiosis remain undefined. Here the authors show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and phys. maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and TH1/TH2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunol. functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine prodn. These findings provide a mol. basis for host-bacterial symbiosis and reveal the archetypal mol. of commensal bacteria that mediates development of the host immune system.
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78Turnbaugh, P. J.; Ley, R. E.; Mahowald, M. A.; Magrini, V.; Mardis, E. R.; Gordon, J. I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027– 1031, DOI: 10.1038/nature0541478https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXjslWgurs%253D&md5=628d0c9769232cc726ebf8f2d19068eeAn obesity-associated gut microbiome with increased capacity for energy harvestTurnbaugh, Peter J.; Ley, Ruth E.; Mahowald, Michael A.; Magrini, Vincent; Mardis, Elaine R.; Gordon, Jeffrey I.Nature (London, United Kingdom) (2006), 444 (7122), 1027-1031CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is assocd. with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through meta-genomic and biochem. analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an addnl. contributing factor to the pathophysiol. of obesity.
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79Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C. P. M.; Alou, M. T.; Daillère, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M. P. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science 2018, 359, 91– 97, DOI: 10.1126/science.aan370679https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXjslOrsw%253D%253D&md5=a095f1934782cd73323256ab75957462Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumorsRouty, Bertrand; Le Chatelier, Emmanuelle; Derosa, Lisa; Duong, Connie P. M.; Alou, Maryam Tidjani; Daillere, Romain; Fluckiger, Aurelie; Messaoudene, Meriem; Rauber, Conrad; Roberti, Maria P.; Fidelle, Marine; Flament, Caroline; Poirier-Colame, Vichnou; Opolon, Paule; Klein, Christophe; Iribarren, Kristina; Mondragon, Laura; Jacquelot, Nicolas; Qu, Bo; Ferrere, Gladys; Clemenson, Celine; Mezquita, Laura; Masip, Jordi Remon; Naltet, Charles; Brosseau, Solenn; Kaderbhai, Coureche; Richard, Corentin; Rizvi, Hira; Levenez, Florence; Galleron, Nathalie; Quinquis, Benoit; Pons, Nicolas; Ryffel, Bernhard; Minard-Colin, Veronique; Gonin, Patrick; Soria, Jean-Charles; Deutsch, Eric; Loriot, Yohann; Ghiringhelli, Francois; Zalcman, Gerard; Goldwasser, Francois; Escudier, Bernard; Hellmann, Matthew D.; Eggermont, Alexander; Raoult, Didier; Albiges, Laurence; Kroemer, Guido; Zitvogel, LaurenceScience (Washington, DC, United States) (2018), 359 (6371), 91-97CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clin. responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome compn. Antibiotics inhibited the clin. benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clin. responses to ICIs and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.
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80Matson, V.; Fessler, J.; Bao, R.; Chongsuwat, T.; Zha, Y.; Alegre, M. L.; Luke, J. J.; Gajewski, T. F. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018, 359, 104– 108, DOI: 10.1126/science.aao329080https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXjslOksg%253D%253D&md5=961e9b039d3cdb440d618640ad218dadThe commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patientsMatson, Vyara; Fessler, Jessica; Bao, Riyue; Chongsuwat, Tara; Zha, Yuanyuan; Alegre, Maria-Luisa; Luke, Jason J.; Gajewski, Thomas F.Science (Washington, DC, United States) (2018), 359 (6371), 104-108CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential compn. of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclin. mouse models. The authors analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S rRNA gene sequencing, metagenomic shotgun sequencing, and quant. polymerase chain reaction for selected bacteria. A significant assocn. was obsd. between commensal microbial compn. and clin. response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. The authors' results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.
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81Belizário, J. E.; Napolitano, M. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front. Microbiol. 2015, 6, 1050, DOI: 10.3389/fmicb.2015.0105081https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28zlslWmtA%253D%253D&md5=9c50c0d119d45e1f45a9d16073e0eda2Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approachesBelizario Jose E; Napolitano MauroFrontiers in microbiology (2015), 6 (), 1050 ISSN:1664-302X.The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.
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82Rinninella, E.; Raoul, P.; Cintoni, M.; Franceschi, F.; Miggiano, G. A. D.; Gasbarrini, A.; Mele, M. C. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms 2019, 7, 14, DOI: 10.3390/microorganisms701001482https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1ShsbjF&md5=388f6272007c7539cbd95a26581cabefWhat is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseasesRinninella, Emanuele; Raoul, Pauline; Cintoni, Marco; Franceschi, Francesco; Miggiano, Giacinto Abele Donato; Gasbarrini, Antonio; Mele, Maria CristinaMicroorganisms (2019), 7 (1), 14CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metab., maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human's gut microbiota are shaped in early life as their compn. depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota compn. since it is different for each individual. However, a healthy host-microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is assocd. not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurol. disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota compn. should be useful in developing promising therapeutic interventions.
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83Cresci, G. A. M.; Izzo, K. Chapter 4 - Gut Microbiome. In Adult Short Bowel Syndrome; Corrigan, M. L., Roberts, K., Steiger, E., Eds.; Academic Press, 2019; pp 45– 54.There is no corresponding record for this reference.
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84CAS Content Collection. https://www.cas.org/about/cas-content (accessed January 18, 2023).There is no corresponding record for this reference.
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85Kho, Z. Y.; Lal, S. K. The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Front. Microbiol. 2018, 9, 1835, DOI: 10.3389/fmicb.2018.0183585https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3islyitA%253D%253D&md5=b3201161709507f19e152a0a0481abf2The Human Gut Microbiome - A Potential Controller of Wellness and DiseaseKho Zhi Y; Lal Sunil KFrontiers in microbiology (2018), 9 (), 1835 ISSN:1664-302X.Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
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86Sankar, S. A.; Lagier, J. C.; Pontarotti, P.; Raoult, D.; Fournier, P. E. The human gut microbiome, a taxonomic conundrum. Syst. Appl. Microbiol 2015, 38, 276– 286, DOI: 10.1016/j.syapm.2015.03.00486https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXls1GktL0%253D&md5=c6f708049d43e2ba4bb0111faae14855The human gut microbiome, a taxonomic conundrumSankar, Senthil Alias; Lagier, Jean-Christophe; Pontarotti, Pierre; Raoult, Didier; Fournier, Pierre-EdouardSystematic and Applied Microbiology (2015), 38 (4), 276-286CODEN: SAMIDF; ISSN:0723-2020. (Elsevier GmbH)From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geog. origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested assocns. between specific gut microbiota compns. and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health.
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87Manson, J. M.; Rauch, M.; Gilmore, M. S. The Commensal Microbiology of the Gastrointestinal Tract. In GI Microbiota and Regulation of the Immune System; Huffnagle, G. B., Noverr, M. C., Eds.; Landes Bioscience and Springer Science+Business Media, LLC: New York, 2008; pp 15– 28.There is no corresponding record for this reference.
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88Kim, D.-H. Gut Microbiota-Mediated Drug-Antibiotic Interactions. Drug Metab. Dispos. 2015, 43, 1581– 1589, DOI: 10.1124/dmd.115.06386788https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1Sgu7fF&md5=d479e92f2c129a8ded40ea9b9c743555Gut microbiota-mediated drug-antibiotic interactionsKim, Dong-HyunDrug Metabolism & Disposition (2015), 43 (10), 1581-1589CODEN: DMDSAI; ISSN:1521-009X. (American Society for Pharmacology and Experimental Therapeutics)Xenobiotic metab. involves the biochem. modification of drugs and phytochems. in living organisms, including humans and other animals. In the intestine, the gut microbiota catalyzes the conversion of hydrophilic drugs into absorbable, hydrophobic compds. through hydroxyzation and redn. Drugs and phytochems. are transformed into bioactive (sulfasalazine, lovastatin, and ginsenoside Rb1), bioinactive (chloramphenicol, ranitidine, and metronidazole), and toxic metabolites (nitrazepam), thus affecting the pharmacokinetics of the original compds. Antibiotics suppress the activities of drug-metabolizing enzymes by inhibiting the proliferation of gut microbiota. Antibiotic treatment might influence xenobiotic metabs. more extensively and potently than previously recognized and reduce gut microbiotamediated transformation of orally administered drugs, thereby altering the systemic concns. of intact drugs, their metabolites, or both. This review describes the effects of antibiotics on the metab. of drugs and phytochems. by the gut microbiota.
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89Deng, P.; Swanson, K. S. Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges. Br. J. Nutr. 2015, 113 (Suppl), S6– 17, DOI: 10.1017/S000711451400294389https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjtlSlu7w%253D&md5=3d61cf86b3eea97f65aacc02f12e8306Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challengesDeng, Ping; Swanson, Kelly S.British Journal of Nutrition (2015), 113 (S1), S6-S17CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)A review. High-throughput DNA sequencing techniques allow for the identification and characterization of microbes and their genes (microbiome). Using these new techniques, microbial populations in several niches of the human body, including the oral and nasal cavities, skin, urogenital tract and gastrointestinal tract, have been described recently. Very little data on the microbiome of companion animals exist, and most of the data have been derived from the anal. of the faeces of healthy lab. animals. High-throughput assays provide opportunities to study the complex and dense populations of the gut microbiota, including bacteria, archaea, fungi, protozoa and viruses. Our lab. and others have recently described the predominant microbial taxa and genes of healthy dogs and cats and how these respond to dietary interventions. In general, faecal microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) and functional capacity (e.g. major functional groups related to carbohydrate, protein, DNA and vitamin metab.; virulence factors; and cell wall and capsule) of the canine and feline gut are similar to those of the human gut. Initial sequencing projects have provided a glimpse of the microbial super-organism that exists within the canine and feline gut, but leaves much to be explored and discovered. As DNA provides information only about potential functions, studies that focus on the microbial transcriptome, metabolite profiles, and how microbiome changes affect host physiol. and health are clearly required. Future studies must det. how diet compn., antibiotics and other drug therapies, breed and disease affect or are affected by the gut microbiome and how this information may be used to improve diets, identify disease biomarkers and develop targeted disease therapies.
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90Nardone, G.; Compare, D. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?. United European Gastroenterol J. 2015, 3, 255– 260, DOI: 10.1177/205064061456684690https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlyitr3O&md5=a6730cf0d3575ef11cdbeb4572753272The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?Nardone, Gerardo; Compare, DeboraUnited European Gastroenterology Journal (2015), 3 (3), 255-260CODEN: UEGJAZ; ISSN:2050-6414. (Sage Publications Ltd.)Introduction: Although long thought to be a sterile organ, due to its acid prodn., the human stomach holds a core microbiome. Aim: To provide an update of findings related to gastric microbiota and its link with gastric diseases. Methods: We conducted a systematic review of the literature. Results: The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the compn. of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual's risk of gastric disease, including gastric cancer. Conclusions: The maintenance of bacterial homeostasis could be essential for the stomach's health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task.
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91Ghosh, S.; Pramanik, S. Structural diversity, functional aspects and future therapeutic applications of human gut microbiome. Arch. Microbiol. 2021, 203, 5281– 5308, DOI: 10.1007/s00203-021-02516-y91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvVaju77K&md5=bf4e1881a45d2b81d40bc769418a59aaStructural diversity, functional aspects and future therapeutic applications of human gut microbiomeGhosh, Soma; Pramanik, SreemantaArchives of Microbiology (2021), 203 (9), 5281-5308CODEN: AMICCW; ISSN:0302-8933. (Springer)Abstr.: The research on human gut microbiome, regarded as the black box of the human body, is still at the stage of infancy as the functional properties of the complex gut microbiome have not yet been understood. Ongoing metagenomic studies have deciphered that the predominant microbial communities belong to eubacterial phyla Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Cyanobacteria, Verrucomicrobia and archaebacterial phylum Euryarchaeota. The indigenous commensal microbial flora prevents opportunistic pathogenic infection and play undeniable roles in digestion, metabolite and signaling mol. prodn. and controlling host's cellular health, immunity and neuropsychiatric behavior. Besides maintaining intestinal health via short-chain fatty acid (SCFA) prodn., gut microbes also aid in neuro-immuno-endocrine modulatory mol. prodn., immune cell differentiation and glucose and lipid metab. Interdependence of diet and intestinal microbial diversity suggests the effectiveness of pre- and pro-biotics in maintenance of gut and systemic health. Several companies worldwide have started potentially exploiting the microbial contribution to human health and have translated their use in disease management and therapeutic applications. The present review discusses the vast diversity of microorganisms playing intricate roles in human metab. The contribution of the intestinal microbiota to regulate systemic activities including gut-brain-immunity crosstalk has been focused. To the best of our knowledge, this review is the first of its kind to collate and discuss the companies worldwide translating the multi-therapeutic potential of human intestinal microbiota, based on the multi-omics studies, i.e. metagenomics and metabolomics, as ready solns. for several metabolic and systemic disorders. Graphic abstr.: [graphic not available: see fulltext].
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92Leser, T. D.; Mo̷lbak, L. Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the host. Environ. Microbiol. 2009, 11, 2194– 2206, DOI: 10.1111/j.1462-2920.2009.01941.x92https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXht1GntrbP&md5=27a4195b0faaab89256c21d3b1bc4e33Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the hostLeser, Thomas D.; Moelbak, LarsEnvironmental Microbiology (2009), 11 (9), 2194-2206CODEN: ENMIFM; ISSN:1462-2912. (Wiley-Blackwell)A review. Mammals live in a homeostatic symbiosis with their gastrointestinal microbiota. The mammalian host provides the microbiota with nutrients and a stable environment; whereas the microbiota helps shaping the host's gut mucosa and provides nutritional contributions. Microorganisms start colonizing the gut immediately after birth followed by a succession of populations until a stable, adult microbiota has been established. However, physiol. conditions differ substantially among locations in the gut and det. bacterial d. and diversity. While Firmicutes and Bacteroidetes dominate the gut microbiota in all mammals, the bacterial genera and species diversity is huge and reflects mammalian phylogeny. The main function of the gastrointestinal epithelium is to absorb nutrients and to retain water and electrolytes, yet at the same time it is an efficient barrier against harmful compds. and microorganisms, and is able to neutralize antagonists coincidentally breaching the barrier. These processes are influenced by the microbiota, which modify epithelial expression of genes involved in nutrient uptake and metab., mucosal barrier function, xenobiotic metab., enteric nervous system and motility, hormonal and maturational responses, angiogenesis, cytoskeleton and extracellular matrix, signal transduction, and general cellular functions. Whereas such effects are local at the gut epithelium they may eventually have systemic consequences, e.g. on body wt. and compn.
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93Linares, D. M.; Ross, P.; Stanton, C. Beneficial Microbes: The pharmacy in the gut. Bioengineered 2016, 7, 11– 20, DOI: 10.1080/21655979.2015.112601593https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XkvFOjsb0%253D&md5=7070a47d0046a1853be4e8dceedf69aeBeneficial Microbes: The pharmacy in the gutLinares, Daniel M.; Ross, Paul; Stanton, CatherineBioengineered (2016), 7 (1), 11-20CODEN: BIOEGL; ISSN:2165-5987. (Taylor & Francis, Inc.)The scientific evidence supporting the gut microbiome in relation to health maintenance and links with various disease states afflicting humans, from metabolic to mental health, has grown dramatically in the last few years. Strategies addressing the pos. modulation of microbiome functionality assocd. with these disorders offer huge potential to the food and pharmaceutical industries to innovate and provide therapeutic solns. to many of the health issues affecting modern society. Such strategies may involve the use of probiotics and prebiotics as nutritional adjunct therapies. Probiotics are generally recognized to be a good form of therapy to keep harmful, intestinal microorganisms in check, aid digestion and nutrient absorption, and contribute to immune function. Probiotics are reported to improve microbial balance in the intestinal tract and promote the return to a baseline microbial community following a perturbing event (dysbiosis) such as antibiotic therapy. Prebiotics are selectively fermented ingredients that allow specific changes, both in the compn. and/or activity in the gastrointestinal microflora, which confers benefits upon host well-being and health.
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94Shah, H. N.; Olsen, I.; Bernard, K.; Finegold, S. M.; Gharbia, S.; Gupta, R. S. Approaches to the study of the systematics of anaerobic, Gram-negative, non-sporeforming rods: Current status and perspectives. Anaerobe 2009, 15, 179– 194, DOI: 10.1016/j.anaerobe.2009.08.00394https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtlChurfL&md5=7db4a2390acafa75bfbdaab154fa032fApproaches to the study of the systematics of anaerobic, Gram-negative, non-spore forming rods: Current status and perspectivesShah, Haroun N.; Olsen, Ingar; Bernard, Kathy; Finegold, Sydney M.; Gharbia, Saheer; Gupta, Radhey S.Anaerobe (2009), 15 (5), 179-194CODEN: ANAEF8; ISSN:1075-9964. (Elsevier Ltd.)A review. The present article gives an overview of recent taxonomic changes among the Gram-neg., anaerobic rods, briefly highlighting areas where the biol. and ecol. have a bearing on recent nomenclatorial changes. The focus is among the genera Bacteroides, Prevotella, Porphyromonas, Leptotrichia, Dysgonomonas, Fusobacterium and the Synergistes group and addnl. demonstrates the value of conserved indels and group-specific proteins for identifying and circumscribing many of these taxa and the Bacteroidetes-Chlorobi species in general.
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95Thomas, F.; Hehemann, J.-H.; Rebuffet, E.; Czjzek, M.; Michel, G. Environmental and Gut Bacteroidetes: The Food Connection. Front. Microbiol. 2011, 2, 93, DOI: 10.3389/fmicb.2011.0009395https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MnntlGnug%253D%253D&md5=0261db88b24d98213748c16711290e03Environmental and gut bacteroidetes: the food connectionThomas Francois; Hehemann Jan-Hendrik; Rebuffet Etienne; Czjzek Mirjam; Michel GurvanFrontiers in microbiology (2011), 2 (), 93 ISSN:.Members of the diverse bacterial phylum Bacteroidetes have colonized virtually all types of habitats on Earth. They are among the major members of the microbiota of animals, especially in the gastrointestinal tract, can act as pathogens and are frequently found in soils, oceans and freshwater. In these contrasting ecological niches, Bacteroidetes are increasingly regarded as specialists for the degradation of high molecular weight organic matter, i.e., proteins and carbohydrates. This review presents the current knowledge on the role and mechanisms of polysaccharide degradation by Bacteroidetes in their respective habitats. The recent sequencing of Bacteroidetes genomes confirms the presence of numerous carbohydrate-active enzymes covering a large spectrum of substrates from plant, algal, and animal origin. Comparative genomics reveal specific Polysaccharide Utilization Loci shared between distantly related members of the phylum, either in environmental or gut-associated species. Moreover, Bacteroidetes genomes appear to be highly plastic and frequently reorganized through genetic rearrangements, gene duplications and lateral gene transfers (LGT), a feature that could have driven their adaptation to distinct ecological niches. Evidence is accumulating that the nature of the diet shapes the composition of the intestinal microbiota. We address the potential links between gut and environmental bacteria through food consumption. LGT can provide gut bacteria with original sets of utensils to degrade otherwise refractory substrates found in the diet. A more complete understanding of the genetic gateways between food-associated environmental species and intestinal microbial communities sheds new light on the origin and evolution of Bacteroidetes as animals' symbionts. It also raises the question as to how the consumption of increasingly hygienic and processed food deprives our microbiota from useful environmental genes and possibly affects our health.
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96McKee, L. S.; La Rosa, S. L.; Westereng, B.; Eijsink, V. G.; Pope, P. B.; Larsbrink, J. Polysaccharide degradation by the Bacteroidetes: mechanisms and nomenclature. Environ. Microbiol. Rep. 2021, 13, 559– 581, DOI: 10.1111/1758-2229.1298096https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhslylt7fK&md5=62fc8423173fefa31728f517b684318cPolysaccharide degradation by the Bacteroidetes: mechanisms and nomenclatureMcKee, Lauren S.; La Rosa, Sabina Leanti; Westereng, Bjoerge; Eijsink, Vincent G.; Pope, Phillip B.; Larsbrink, JohanEnvironmental Microbiology Reports (2021), 13 (5), 559-581CODEN: EMRNAG; ISSN:1758-2229. (Wiley-Blackwell)The Bacteroidetes phylum is renowned for its ability to degrade a wide range of complex carbohydrates, a trait that has enabled its dominance in many diverse environments. The best studied species inhabit the human gut microbiome and use polysaccharide utilization loci (PULs), discrete genetic structures that encode proteins involved in the sensing, binding, deconstruction, and import of target glycans. In many environmental species, polysaccharide degrdn. is tightly coupled to the phylum-exclusive type IX secretion system (T9SS), which is used for the secretion of certain enzymes and is linked to gliding motility. In addn., within specific species these two adaptive systems (PULs and T9SS) are intertwined, with PUL-encoded enzymes being secreted by the T9SS. Here, we discuss the most noteworthy PUL and non-PUL mechanisms that confer specific and rapid polysaccharide degrdn. capabilities to the Bacteroidetes in a range of environments. We also acknowledge that the literature showcasing examples of PULs is rapidly expanding and developing a set of assumptions that can be hard to track back to original findings. Therefore, we present a simple universal description of conserved PUL functions and how they are detd., while proposing a common nomenclature describing PULs and their components, to simplify discussion and understanding of PUL systems.
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97Ludwig, W.; Schleifer, K.-H.; Whitman, W. B. Revised road map to the phylum Firmicutes. In Bergey’s Manual of Systematic Bacteriology: Vol. Three The Firmicutes; De Vos, P., Garrity, G. M., Jones, D., Krieg, N. R., Ludwig, W., Rainey, F. A., Schleifer, K.-H., Whitman, W. B., Eds.; Springer New York: New York, 2009; pp 1– 13.There is no corresponding record for this reference.
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98Yang, M.; Gu, Y.; Li, L.; Liu, T.; Song, X.; Sun, Y.; Cao, X.; Wang, B.; Jiang, K.; Cao, H. Bile Acid–Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside. Nutrients 2021, 13, 3143, DOI: 10.3390/nu1309314398https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVKgtrfN&md5=05bbf4ed3aea2831c978ef4758623890Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to BedsideYang, Min; Gu, Yu; Li, Lingfeng; Liu, Tianyu; Song, Xueli; Sun, Yue; Cao, Xiaocang; Wang, Bangmao; Jiang, Kui; Cao, HailongNutrients (2021), 13 (9), 3143CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial compn. marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metab.) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concn. of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.
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99Barka, E. A.; Vatsa, P.; Sanchez, L.; Gaveau-Vaillant, N.; Jacquard, C.; Klenk, H.-P.; Clément, C.; Ouhdouch, Y.; Wezel, G. P. v. Taxonomy, Physiology, and Natural Products of Actinobacteria. Microbiology and Molecular Biology Reviews 2016, 80, 1– 43, DOI: 10.1128/MMBR.00019-1599https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28vls1Sjtg%253D%253D&md5=dac99309cc12275c1dbbc27e457fd9ffTaxonomy, Physiology, and Natural Products of ActinobacteriaBarka Essaid Ait; Vatsa Parul; Sanchez Lisa; Gaveau-Vaillant Nathalie; Jacquard Cedric; Clement Christophe; Meier-Kolthoff Jan P; Klenk Hans-Peter; Ouhdouch Yder; van Wezel Gilles PMicrobiology and molecular biology reviews : MMBR (2016), 80 (1), 1-43 ISSN:.Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum.
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100Hidalgo-Cantabrana, C.; Delgado, S.; Ruiz, L.; Ruas-Madiedo, P.; Sánchez, B.; Margolles, A. Bifidobacteria and Their Health-Promoting Effects. Microbiol Spectr 2017, 5, 5.3.21, DOI: 10.1128/microbiolspec.BAD-0010-2016There is no corresponding record for this reference.
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101Stackebrandt, E.; Murray, R. G. E.; Trüper, H. G. Proteobacteria classis nov., a Name for the Phylogenetic Taxon That Includes the “Purple Bacteria and Their Relatives. International Journal of Systematic and Evolutionary Microbiology 1988, 38, 321– 325, DOI: 10.1099/00207713-38-3-321There is no corresponding record for this reference.
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102Rizzatti, G.; Lopetuso, L. R.; Gibiino, G.; Binda, C.; Gasbarrini, A. Proteobacteria: A Common Factor in Human Diseases. BioMed. Research International 2017, 2017, 9351507, DOI: 10.1155/2017/9351507102https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MzgsVKgsg%253D%253D&md5=ff061232dd3e1d205818520859b76722Proteobacteria: A Common Factor in Human DiseasesRizzatti G; Lopetuso L R; Gibiino G; Binda C; Gasbarrini ABioMed research international (2017), 2017 (), 9351507 ISSN:.Microbiota represents the entire microbial community present in the gut host. It serves several functions establishing a mutualistic relation with the host. Latest years have seen a burst in the number of studies focusing on this topic, in particular on intestinal diseases. In this scenario, Proteobacteria are one of the most abundant phyla, comprising several known human pathogens. This review highlights the latest findings on the role of Proteobacteria not only in intestinal but also in extraintestinal diseases. Indeed, an increasing amount of data identifies Proteobacteria as a possible microbial signature of disease. Several studies demonstrate an increased abundance of members belonging to this phylum in such conditions. Major evidences currently involve metabolic disorders and inflammatory bowel disease. However, more recent studies suggest a role also in lung diseases, such as asthma and chronic obstructive pulmonary disease, but evidences are still scant. Notably, all these conditions are sustained by various degree of inflammation, which thus represents a core aspect of Proteobacteria-related diseases.
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103Lee, K.-C.; Webb, R. I.; Janssen, P. H.; Sangwan, P.; Romeo, T.; Staley, J. T.; Fuerst, J. A. Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes. BMC Microbiol. 2009, 9, 5, DOI: 10.1186/1471-2180-9-5103https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M7msFyitQ%253D%253D&md5=d528d371ef74f6683ff411a93595b264Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum PlanctomycetesLee Kuo-Chang; Webb Richard I; Janssen Peter H; Sangwan Parveen; Romeo Tony; Staley James T; Fuerst John ABMC microbiology (2009), 9 (), 5 ISSN:.BACKGROUND: The phylum Verrucomicrobia is a divergent phylum within domain Bacteria including members of the microbial communities of soil and fresh and marine waters; recently extremely acidophilic members from hot springs have been found to oxidize methane. At least one genus, Prosthecobacter, includes species with genes homologous to those encoding eukaryotic tubulins. A significant superphylum relationship of Verrucomicrobia with members of phylum Planctomycetes possessing a unique compartmentalized cell plan, and members of the phylum Chlamydiae including human pathogens with a complex intracellular life cycle, has been proposed. Based on the postulated superphylum relationship, we hypothesized that members of the two separate phyla Planctomycetes and Verrucomicrobia might share a similar ultrastructure plan differing from classical prokaryote organization. RESULTS: The ultrastructure of cells of four members of phylum Verrucomicrobia - Verrucomicrobium spinosum, Prosthecobacter dejongeii, Chthoniobacter flavus, and strain Ellin514 - was examined using electron microscopy incorporating high-pressure freezing and cryosubstitution. These four members of phylum Verrucomicrobia, representing 3 class-level subdivisions within the phylum, were found to possess a compartmentalized cell plan analogous to that found in phylum Planctomycetes. Like all planctomycetes investigated, they possess a major pirellulosome compartment containing a condensed nucleoid and ribosomes surrounded by an intracytoplasmic membrane (ICM), as well as a ribosome-free paryphoplasm compartment between the ICM and cytoplasmic membrane. CONCLUSION: A unique compartmentalized cell plan so far found among Domain Bacteria only within phylum Planctomycetes, and challenging our concept of prokaryote cell plans, has now been found in a second phylum of the Domain Bacteria, in members of phylum Verrucomicrobia. The planctomycete cell plan thus occurs in at least two distinct phyla of the Bacteria, phyla which have been suggested from other evidence to be related phylogenetically in the proposed PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) superphylum. This planctomycete cell plan is present in at least 3 of 6 subdivisions of Verrucomicrobia, suggesting that the common ancestor of the verrucomicrobial phylum was also compartmentalized and possessed such a plan. The presence of this compartmentalized cell plan in both phylum Planctomycetes and phylum Verrucomicrobia suggest that the last common ancestor of these phyla was also compartmentalized.
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104Rappé, M. S.; Giovannoni, S. J. The Uncultured Microbial Majority. Annu. Rev. Microbiol. 2003, 57, 369– 394, DOI: 10.1146/annurev.micro.57.030502.090759104https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXptFWlsr8%253D&md5=8f5a003db3f5d19683c2ebecfb40e125The uncultured microbial majorityRappe, Michael S.; Giovannoni, Stephen J.Annual Review of Microbiology (2003), 57 (), 369-394CODEN: ARMIAZ; ISSN:0066-4227. (Annual Reviews Inc.)A review. Since the delineation of 12 bacterial phyla by comparative phylogenetic analyses of 16S rRNA in 1987, knowledge of microbial diversity has expanded dramatically owing to the sequencing of rRNA genes cloned from environmental DNA. Currently, only 26 of the approx. 52 identifiable major lineages, or phyla, within the domain Bacteria have cultivated representatives. Evidence from field studies indicates that many of the uncultivated phyla are found in diverse habitats, and some are extraordinarily abundant. In some important environments, including seawater, freshwater, and soil, many biol. and geochem. important organisms are at best only remotely related to any strain that has been characterized by phenotype or by genome sequencing. Genome sequence information that would allow rRNA gene trees to be related to broader patterns in microbial genome evolution is scant, and therefore microbial diversity remains largely unexplored territory.
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105Geerlings, S. Y.; Ouwerkerk, J. P.; Koehorst, J. J.; Ritari, J.; Aalvink, S.; Stecher, B.; Schaap, P. J.; Paulin, L.; de Vos, W. M.; Belzer, C. Genomic convergence between Akkermansia muciniphila in different mammalian hosts. BMC Microbiol. 2021, 21, 298, DOI: 10.1186/s12866-021-02360-6105https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVeiur%252FJ&md5=fc1edb781f16cb7d3e74f2063be471a8Genomic convergence between Akkermansia muciniphila in different mammalian hostsGeerlings, Sharon Y.; Ouwerkerk, Janneke P.; Koehorst, Jasper J.; Ritari, Jarmo; Aalvink, Steven; Stecher, Baerbel; Schaap, Peter J.; Paulin, Lars; de Vos, Willem M.; Belzer, ClaraBMC Microbiology (2021), 21 (1), 298CODEN: BMMIBC; ISSN:1471-2180. (BioMed Central Ltd.)Akkermansia muciniphila is a member of the human gut microbiota where it resides in the mucus layer and uses mucin as the sole carbon, nitrogen and energy source. A. muciniphila is the only representative of the Verrucomicrobia phylum in the human gut. However, A. muciniphila 16S rRNA gene sequences have also been found in the intestines of many vertebrates. We detected A. muciniphila-like bacteria in the intestines of animals belonging to 15 out of 16 mammalian orders. In addn., other species belonging to the Verrucomicrobia phylum were detected in fecal samples. We isolated 10 new A. muciniphila strains from the feces of chimpanzee, siamang, mouse, pig, reindeer, horse and elephant. The physiol. and genome of these strains were highly similar in comparison to the type strain A. muciniphila MucT. Overall, the genomes of the new strains showed high av. nucleotide identity (93.9 to 99.7%). In these genomes, we detected considerable conservation of at least 75 of the 78 mucin degrdn. genes that were previously detected in the genome of the type strain MucT. The low genomic divergence obsd. in the new strains may indicate that A. muciniphila favors mucosal colonization independent of the differences in hosts. In addn., the conserved mucus degrdn. capability points towards a similar beneficial role of the new strains in regulating host metabolic health.
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106Liu, M.-J.; Yang, J.-Y.; Yan, Z.-H.; Hu, S.; Li, J.-Q.; Xu, Z.-X.; Jian, Y.-P. Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases. Clin. Nutr. 2022, 41, 2333– 2344, DOI: 10.1016/j.clnu.2022.08.029106https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFCqur3N&md5=8427cc10cfe52ddeada931c698ff2bf9Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseasesLiu, Meng-Jie; Yang, Jing-Yu; Yan, Zhen-Hua; Hu, Shuang; Li, Jun-Qi; Xu, Zhi-Xiang; Jian, Yong-PingClinical Nutrition (2022), 41 (10), 2333-2344CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)A review. The mammalian gastrointestinal tract is colonized with a majority of gut microbes, affecting host metab. and homeostasis. Gut microbiota plays a vital role in nutrient exchange, signaling transduction between intestinal epithelial cells, and resistance to pathogen invasion. Gut microbiota is divided into mucus layer bacteria and intestinal lumen bacteria based on the colonization distribution. Akkermansia muciniphila (A. muciniphila) prefers to colonize in the intestinal mucus layer, and specifically degrades mucins to produce short-chain fatty acids, providing energy for the host and promoting colonization of the bacterium itself. Degrdn. of mucins prompts the host to compensate for the prodn. of more mucins, thereby maintaining the dynamics of these proteins. In the intestinal micro-ecosystem, A. muciniphila is non-pathogenic, and its colonization with suitable abundance contributes to the development of immune system, thus promoting intestinal health. The mechanisms by which A. muciniphila bears a protective role in the host intestine are currently unclear. We summarize the microenvironment for the colonization of A. muciniphila, physiol. characteristics and pathophysiol. impact of A. muciniphila on intestinal diseases, such as irritable bowel syndrome, inflammatory bowel diseases, and intestinal tumors. We also provided updates for current studies on signals that A. muciniphila enhances intestinal barrier integrity and regulates immune response. Together, we conclude that A. muciniphila is a promising probiotic, which could be a microbial target for the treatment of multiple intestinal diseases.
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107Gupta, R. S.; Sethi, M. Phylogeny and molecular signatures for the phylum Fusobacteria and its distinct subclades. Anaerobe 2014, 28, 182– 198, DOI: 10.1016/j.anaerobe.2014.06.007107https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlCltLvM&md5=e31bb61fa4c7b945081a26c98b3d8573Phylogeny and molecular signatures for the phylum Fusobacteria and its distinct subcladesGupta, Radhey S.; Sethi, MohitAnaerobe (2014), 28 (), 182-198CODEN: ANAEF8; ISSN:1075-9964. (Elsevier Ltd.)The members of the phylum Fusobacteria and its two families, Fusobacteriaceae and Leptotrichiaceae, are distinguished at present mainly on the basis of their branching in the 16S rRNA gene trees and anal. of the internal transcribed spacer sequences in the 16S-23S rDNA. However, no biochem. or mol. characteristics are known that are uniquely shared by all of most members of these groups of bacteria. We report here detailed phylogenetic and comparative analyses on 45 sequenced Fusobacteria genomes to examine their evolutionary relationships and to identify mol. markers that are specific for the members of this phylum. In phylogenetic trees based on 16S rRNA gene sequences or concatenated sequences for 17 conserved proteins, members of the families Fusobacteriaceae and Leptotrichiaceae formed strongly supported clades and were clearly distinguished. In these trees, the species from the genus Fusobacterium also formed a no. of well-supported clades. In parallel, comparative analyses on Fusobacteria genomes have identified 44 conserved signature indels (CSIs) in proteins involved in a broad range of functions that are either specific for the phylum Fusobacteria or a no. of distinct subclades within this phylum. Seven of these CSIs in important proteins are uniquely present in the protein homologs of all sequenced Fusobacteria and they provide potential mol. markers for this phylum. Six and three other CSIs in other protein sequences are specific for members of the families Fusobacteriaceae and Leptotrichiaceae, resp., and they provide novel mol. means for distinguishing members of these two families. Fourteen addnl. CSIs in different proteins, which are specific for either members of the genera Fusobacterium or Leptotrichia, or a no. of other well-supported clades of Fusobacteria at multiple phylogenetic levels, provide mol. markers for these groups and information regarding the evolutionary relationships among the members of this phylum. Lastly, the present work has also identified 14 CSIs in divergent proteins that are specific for three specific subclades of Fusobacterium species, which are also indicated to be distinct by phylogenetic analyses. The members of these three Fusobacterium subclades also differ significantly from each other in their whole genome av. nucleotide identities values, suggesting that they are possible candidates for recognition as different genera. The mol. markers reported here provide novel means for the identification of members of the phylum Fusobacteria and for their classification.
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108Madhogaria, B.; Bhowmik, P.; Kundu, A. Correlation between human gut microbiome and diseases. Infectious Medicine 2022, 1, 180– 191, DOI: 10.1016/j.imj.2022.08.004There is no corresponding record for this reference.
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109Bull, M. J.; Plummer, N. T. Part 1: The Human Gut Microbiome in Health and Disease. Integr. Med. 2014, 13, 17– 22109https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28ngslCqtg%253D%253D&md5=1e800609aae342509788de2879a22170Part 1: The Human Gut Microbiome in Health and DiseaseBull Matthew J; Plummer Nigel TIntegrative medicine (Encinitas, Calif.) (2014), 13 (6), 17-22 ISSN:1546-993X.The bacterial cells harbored within the human gastrointestinal tract (GIT) outnumber the host's cells by a factor of 10 and the genes encoded by the bacteria resident within the GIT outnumber their host's genes by more than 100 times. These human digestive-tract associated microbes are referred to as the gut microbiome. The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physiology, and immune function. Imbalance of the normal gut microbiota have been linked with gastrointestinal conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and wider systemic manifestations of disease such as obesity, type 2 diabetes, and atopy. In the first part of this review, we evaluate our evolving knowledge of the development, complexity, and functionality of the healthy gut microbiota, and the ways in which the microbial community is perturbed in dysbiotic disease states; the second part of this review covers the role of interventions that have been shown to modulate and stabilize the gut microbiota and also to restore it to its healthy composition from the dysbiotic states seen in IBS, IBD, obesity, type 2 diabetes, and atopy.
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110Vijay, A.; Valdes, A. M. Role of the gut microbiome in chronic diseases: a narrative review. Eur. J. Clin. Nutr. 2022, 76, 489– 501, DOI: 10.1038/s41430-021-00991-6110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjsVOntbc%253D&md5=df621b3f9e2bfd638c58c1209db0de71Role of the gut microbiome in chronic diseases: a narrative reviewVijay, Amrita; Valdes, Ana M.European Journal of Clinical Nutrition (2022), 76 (4), 489-501CODEN: EJCNEQ; ISSN:0954-3007. (Nature Portfolio)A review. The gut microbiome, i.e., the community of bacteria and other microorganisms living in the human gut, has been implicated both directly and indirectly (mediating the effects of diet) on human health. The assocns. between gut microbiome compn. and disease status have been widely reported, while recent studies have demonstrated a role for the gut microbiome in influencing remote organs, mucosal, and immune function. This review details the role of the gut microbiome in chronic diseases and ways it can be modulated for the management or prevention of chronic conditions. The aim of this narrative review is to describe the assocns. between gut microbiome compn. and various types of chronic diseases and to discuss the links to habitual diet and dietary components. Discussed here is the gut microbiome compn. and its assocn. with autoimmune diseases, gut inflammation/bowel disorders, cardiometabolic diseases, chronic kidney disease (CKD). Finally, the gut microbiome is studied as a therapeutic target in the treatment of chronic diseases.
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111Baquero, F.; Nombela, C. The microbiome as a human organ. Clin Microbiol Infect 2012, 18 (Suppl 4), 2– 4, DOI: 10.1111/j.1469-0691.2012.03916.x111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFOrsr7J&md5=83369e0cc4a735dd21ea26982b23bd9eThe microbiome as a human organBaquero, F.; Nombela, C.Clinical Microbiology and Infection (2012), 18 (Suppl. 4), 2-4CODEN: CMINFM; ISSN:1198-743X. (Wiley-Blackwell)A review. The human organism is a complex structure composed of cells belonging to all three domains of life on Earth, Eukarya, Bacteria and Archaea, as well as their viruses. Bacterial cells of more than a thousand taxonomic units are condensed in a particular functional collective domain, the intestinal microbiome. The microbiome constitutes the last human organ under active research. Like other organs, and despite its intrinsic complexity, the microbiome is readily inherited, in a process probably involving 'small world' power law dynamics of construction in newborns. Like any other organ, the microbiome has physiol. and pathol., and the individual (and collective) health might be damaged when its collective population structure is altered. The diagnostic of microbiomic diseases involves metagenomic studies. The therapeutics of microbiome-induced pathol. include microbiota transplantation, a technique increasingly available. Perhaps a new medical specialty, microbiomol., is being born.
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112Evans, J. M.; Morris, L. S.; Marchesi, J. R. The gut microbiome: the role of a virtual organ in the endocrinology of the host. J. Endocrinol. 2013, 218, R37– R47, DOI: 10.1530/JOE-13-0131112https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1WltLjF&md5=3ab2a34ea51b8140d352b87e480f1b0aThe gut microbiome: the role of a virtual organ in the endocrinology of the hostEvans, James M.; Morris, Laura S.; Marchesi, Julian R.Journal of Endocrinology (2013), 218 (3), R37-R47CODEN: JOENAK; ISSN:0022-0795. (BioScientifica Ltd.)A review. The human microbiome contains a vast array of microbes and genes that show greater complexity than the host's own karyome; the functions of many of these microbes are beneficial and show co-evolution with the host, while others are detrimental. The microbiota that colonises the gut is now being considered as a virtual organ or emergent system, with properties that need to be integrated into host biol. and physiol. Unlike other organs, the functions that the gut microbiota plays in the host are as yet not fully understood and can be quite easily disrupted by antibiotics, diet or surgery. In this review, we look at some of the best-characterised functions that only the gut microbiota plays and how it interacts with the host's endocrine system and we try to make it clear that the 21st-century biol. cannot afford to ignore this facet of biol., if it wants to fully understand what makes us human.
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113Haseeb, A.; Shahzad, I.; Ghulam, H.; Muhammad Naeem, F.; Humaira, M.; Imtiaz, M.; Imran, M.; Saima, M.; Muhammad Irfan, U. Gut Microbiome: A New Organ System in Body. In Parasitology and Microbiology Research; Gilberto Antonio Bastidas, P., Asghar Ali, K., Eds.; IntechOpen: Rijeka, Croatia, 2019.There is no corresponding record for this reference.
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114Cani, P. D. Human gut microbiome: hopes, threats and promises. Gut 2018, 67, 1716– 1725, DOI: 10.1136/gutjnl-2018-316723114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVehtLc%253D&md5=c4f47f74d81d89dee22cc32b466a3f11Human gut microbiome: hopes, threats and promisesCani, Patrice D.Gut (2018), 67 (9), 1716-1725CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)A review. The microbiome has received increasing attention over the last 15 years. Although gut microbes have been explored for several decades, investigations of the role of microorganisms that reside in the human gut has attracted much attention beyond classical infectious diseases. For example, numerous studies have reported changes in the gut microbiota during not only obesity, diabetes, and liver diseases but also cancer and even neurodegenerative diseases. The human gut microbiota is viewed as a potential source of novel therapeutics. Between 2013 and 2017, the no. of publications focusing on the gut microbiota was, remarkably, 12 900, which represents four-fifths of the total no. of publications over the last 40 years that investigated this topic. This review discusses recent evidence of the impact of the gut microbiota on metabolic disorders and focus on selected key mechanisms. This review also aims to provide a crit. anal. of the current knowledge in this field, identify putative key issues or problems and discuss misinterpretations. The abundance of metagenomic data generated on comparing diseased and healthy subjects can lead to the erroneous claim that a bacterium is causally linked with the protection or the onset of a disease. In fact, environmental factors such as dietary habits, drug treatments, intestinal motility and stool frequency and consistency are all factors that influence the compn. of the microbiota and should be considered. The cases of the bacteria Prevotella copri and Akkermansia muciniphila will be discussed as key examples.
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115Lloyd-Price, J.; Arze, C.; Ananthakrishnan, A. N.; Schirmer, M.; Avila-Pacheco, J.; Poon, T. W.; Andrews, E.; Ajami, N. J.; Bonham, K. S.; Brislawn, C. J. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 2019, 569, 655– 662, DOI: 10.1038/s41586-019-1237-9115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVOgtL3O&md5=4376c66207c176377e5b973777fba13bMulti-omics of the gut microbial ecosystem in inflammatory bowel diseasesLloyd-Price, Jason; Arze, Cesar; Ananthakrishnan, Ashwin N.; Schirmer, Melanie; Avila-Pacheco, Julian; Poon, Tiffany W.; Andrews, Elizabeth; Ajami, Nadim J.; Bonham, Kevin S.; Brislawn, Colin J.; Casero, David; Courtney, Holly; Gonzalez, Antonio; Graeber, Thomas G.; Hall, A. Brantley; Lake, Kathleen; Landers, Carol J.; Mallick, Himel; Plichta, Damian R.; Prasad, Mahadev; Rahnavard, Gholamali; Sauk, Jenny; Shungin, Dmitry; Vazquez-Baeza, Yoshiki; White, Richard A., III; Braun, Jonathan; Denson, Lee A.; Jansson, Janet K.; Knight, Rob; Kugathasan, Subra; McGovern, Dermot P. B.; Petrosino, Joseph F.; Stappenbeck, Thaddeus S.; Winter, Harland S.; Clish, Clary B.; Franzosa, Eric A.; Vlamakis, Hera; Xavier, Ramnik J.; Huttenhower, CurtisNature (London, United Kingdom) (2019), 569 (7758), 655-662CODEN: NATUAS; ISSN:0028-0836. (Nature Research)Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clin., immunol., mol., genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal mol. profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as mol. disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochem. shifts. Finally, integrative anal. identified microbial, biochem., and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
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116Mars, R. A. T.; Yang, Y.; Ward, T.; Houtti, M.; Priya, S.; Lekatz, H. R.; Tang, X.; Sun, Z.; Kalari, K. R.; Korem, T. Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome. Cell 2020, 182, 1460– 1473.e17, DOI: 10.1016/j.cell.2020.08.007116https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVajsL3M&md5=75eaf2c7114cfb7251564c30c6687b75Longitudinal multi-omics reveals Subset-Specific Mechanisms Underlying Irritable Bowel SyndromeMars, Ruben A. T.; Yang, Yi; Ward, Tonya; Houtti, Mo; Priya, Sambhawa; Lekatz, Heather R.; Tang, Xiaojia; Sun, Zhifu; Kalari, Krishna R.; Korem, Tal; Bhattarai, Yogesh; Zheng, Tenghao; Bar, Noam; Frost, Gary; Johnson, Abigail J.; van Treuren, Will; Han, Shuo; Ordog, Tamas; Grover, Madhusudan; Sonnenburg, Justin; D'Amato, Mauro; Camilleri, Michael; Elinav, Eran; Segal, Eran; Blekhman, Ran; Farrugia, Gianrico; Swann, Jonathan R.; Knights, Dan; Kashyap, Purna C.Cell (Cambridge, MA, United States) (2020), 182 (6), 1460-1473.e17CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Detg. its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiol. changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiol. We identified IBS subtype-specific and symptom-related variation in microbial compn. and function. A subset of identified changes in microbial metabolites correspond to host physiol. mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metab. as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.
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117Rinttilä, T.; Lyra, A.; Krogius-Kurikka, L.; Palva, A. Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjects. Gut Pathog. 2011, 3, 6, DOI: 10.1186/1757-4749-3-6117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsl2ntb0%253D&md5=4f84e5c6102f7ffaea8fb030757f88c3Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjectsRinttila, Teemu; Lyra, Anna; Krogius-Kurikka, Lotta; Palva, AiriGut Pathogens (2011), 3 (), 6CODEN: GPUAB2; ISSN:1757-4749. (BioMed Central Ltd.)Growing amt. of scientific evidence suggests that microbes are involved in the pathophysiol. of irritable bowel syndrome (IBS). The predominant fecal microbiota compn. of IBS subjects has been widely studied with DNA-based techniques but less research has been focused on the intestinal pathogens in this disorder. Here, we optimized a highly sensitive panel of 12 quant. real-time PCR (qPCR) assays to shed light on the putative presence of intestinal pathogens in IBS sufferers. The panel was used to screen fecal samples from 96 IBS subjects and 23 healthy controls. Fifteen IBS samples (17%) tested pos. for Staphylococcus aureus with a thermonuclease (nuc) gene-targeting qPCR assay, whereas none of the healthy controls were pos. for S. aureus (p < 0.05). The S. aureus-pos. IBS samples were confirmed by sequencing of the PCR amplicons. Clostridium perfringens was detected from IBS and control groups with a similar frequency (13% and 17%, resp.) with α-toxin (plc) gene-targeting qPCR assay while none of the samples tested pos. for the Cl. perfringens enterotoxin-encoding gene (cpe). The qPCR panel consisting of 12 assays for an extensive set of pathogenic microorganisms provides an efficient alternative to the conventional detection of gastrointestinal pathogens and could accelerate the initiation of targeted antibiotic therapy reducing the risk of post-infectious IBS (PI-IBS). S. aureus has not been previously reported to be assocd. with the onset of IBS. Although we discovered significant differences in the prevalence of S. aureus between the study groups, its importance in giving rise to IBS symptoms requires further studies.
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118Mayer, E. A.; Nance, K.; Chen, S. The Gut-Brain Axis. Annu. Rev. Med. 2022, 73, 439– 453, DOI: 10.1146/annurev-med-042320-014032118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cjit1ejsA%253D%253D&md5=e416e85301b2698d90fce325d3075f21The Gut-Brain AxisMayer Emeran A; Nance Karina; Chen ShelleyAnnual review of medicine (2022), 73 (), 439-453 ISSN:.Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Alterations in gut-brain-microbiome interactions have been identified in rodent models of several digestive, psychiatric, and neurological disorders. While alterations in gut-brain interactions have clearly been established in irritable bowel syndrome, a causative role of the microbiome in irritable bowel syndrome remains to be determined. In the absence of specific microbial targets for more effective therapies, current approaches are limited to dietary interventions and centrally targeted pharmacological and behavioral approaches. A more comprehensive understanding of causative influences within the gut-brain-microbiome system and well-designed randomized controlled trials are needed to translate these exciting preclinical findings into effective therapies.
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119Zhang, T.; Zhang, C.; Zhang, J.; Sun, F.; Duan, L. Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis. Front Cell Infect Microbiol 2022, 12, 859967, DOI: 10.3389/fcimb.2022.859967119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MvosVOnsQ%253D%253D&md5=435ad6a1bd9f95fbed238df0e858e8d9Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-AnalysisZhang Tao; Zhang Cunzheng; Zhang Jindong; Duan Liping; Sun Feng; Sun FengFrontiers in cellular and infection microbiology (2022), 12 (), 859967 ISSN:.Background: Irritable bowel syndrome (IBS) is a common gastrointestinal condition. Studies regarding the treatment of IBS with probiotics have not yielded consistent results, and the best probiotics has not yet been confirmed. Therefore, we performed a network meta-analysis (NMA) to assess the relative rank order of different probiotics for IBS. Method: We searched for RCTs on the efficacy of probiotics for IBS until August 25, 2021. The primary outcome was the symptom relief rate, as well as global symptoms, abdominal pain, bloating, and straining scores. The NMA was conducted using Stata 15.0. We also used meta-regression to explore whether the treatment length and dose influenced the efficacy. Results: Forty-three RCTs, with 5,531 IBS patients, were included in this analysis. Firstly, we compared the efficacy of different probiotic species. B.coagulans exhibited the highest probability to be the optimal probiotic specie in improving IBS symptom relief rate, as well as global symptom, abdominal pain, bloating, and straining scores. In regard to the secondary outcomes, L.plantarum ranked first in ameliorating the QOL of IBS patients, but without any significant differences compared with other probiotic species in standardized mean differences (SMD) estimates. Moreover, patients received L.acidophilus had lowest incidence of adverse events. The meta-regression revealed that no significant differences were found between participants using different doses of probiotics in all outcomes, while the treatment length, as a confounder, can significantly influence the efficacy of probiotics in ameliorating abdominal pain (Coef = -2.30; p = 0.035) and straining (Coef = -3.15; p = 0.020) in IBS patients. Thus, we performed the subgroup analysis on treatment length subsequently in these two outcomes, which showed that efficacy of B.coagulans using 8 weeks ranked first both in improving the abdominal pain and straining scores. Additionally, B. coagulans still had significant efficacy compared to different types of probiotic combinations in present study. Conclusions: The findings of this NMA suggested that B.coagulans had prominent efficacy in treating IBS patients, and incorporating B.coagulans into a probiotic combination, or genetically engineering it to amplify its biological function may be a future research target to treat IBS patients. With few direct comparisons available between individual therapies today, this NMA may have utility in forming treatment guideline for IBS with probiotics.
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120Ponnusamy, K.; Choi, J. N.; Kim, J.; Lee, S. Y.; Lee, C. H. Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J. Med. Microbiol. 2011, 60, 817– 827, DOI: 10.1099/jmm.0.028126-0120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXotlyktL8%253D&md5=45cb3406def633eeb56142c42ee8112bMicrobial community and metabolomic comparison of irritable bowel syndrome faecesPonnusamy, Kannan; Choi, Jung Nam; Kim, Jiyoung; Lee, Sun-Young; Lee, Choong HwanJournal of Medical Microbiology (2011), 60 (6), 817-827CODEN: JMMIAV; ISSN:0022-2615. (Society for General Microbiology)Human health relies on the compn. of microbiota in an individual's gut and the synthesized metabolites that may alter the gut environment. Gut microbiota and fecal metabolites are involved in several gastrointestinal diseases. In this study, 16S rRNA-specific denaturing gradient gel electrophoresis and quant. PCR anal. showed that the mean similarity of total bacteria was significantly different (P<0.001) in fecal samples from patients with irritable bowel syndrome (IBS; n=11) and from non-IBS (nIBS) patients (n=8). IBS subjects had a significantly higher diversity of total bacteria, as measured by the Shannon index (H') (3.36<H'<4.37, P=0.004), Bacteroidetes and lactobacilli; however, less diversity was obsd. for Bifidobacter (1.7< H'<3.08, P<0.05) and Clostridium coccoides (0.9< H'<2.98, P=0.007). In this study, no significant difference was found in total bacterial quantity (P>0.05). GC/MS-based multi-variate anal. delineated the fecal metabolites of IBS from nIBS samples. Elevated levels of amino acids (alanine and pyroglutamic acid) and phenolic compds. (hydroxyphenyl acetate and hydroxyphenyl propionate) were found in IBS. These results were highly correlated with the abundance of lactobacilli and Clostridium, which indicates an altered metab. rate assocd. with these gut microorganisms. A higher diversity of Bacteroidetes and Lactobacillus groups in IBS fecal samples also correlated with the resp. total quantity. In addn., these changes altered protein and carbohydrate energy metab. in the gut.
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121Rajilić-Stojanović, M.; Biagi, E.; Heilig, H. G.; Kajander, K.; Kekkonen, R. A.; Tims, S.; de Vos, W. M. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011, 141, 1792– 1801, DOI: 10.1053/j.gastro.2011.07.043121https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtlOksbrN&md5=da9f508d81243c976bedbd98e3d369ecGlobal and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel SyndromeRajilic-Stojanovic, Mirjana; Biagi, Elena; Heilig, Hans G. H. J.; Kajander, Kajsa; Kekkonen, Riina A.; Tims, Sebastian; de Vos, Willem M.Gastroenterology (2011), 141 (5), 1792-1801CODEN: GASTAB; ISSN:0016-5085. (Elsevier)Background & Aims: Irritable bowel syndrome (IBS) has been assocd. with disruptions to the intestinal microbiota, but studies have had limited power, coverage, and depth of anal. We aimed to define microbial populations that can be used discriminate the fecal microbiota of patients with IBS from that of healthy subjects and correlate these with IBS intestinal symptom scores. Methods: The microbiota compn. was assessed by global and deep mol. anal. of fecal samples from 62 patients with IBS patients and 46 healthy individuals (controls). We used a comprehensive and highly reproducible phylogenetic microarray in combination with quant. polymerase chain reaction. Results: The intestinal microbiota of IBS patients differed significantly (P = .0005) from that of controls. The microbiota of patients, compared with controls, had a 2-fold increased ratio of the Firmicutes to Bacteroidetes (P = .0002). This resulted from an approx. 1.5-fold increase in nos. of Dorea, Ruminococcus, and Clostridium spp (P < .005); a 2-fold decrease in the no. of Bacteroidetes (P < .0001); a 1.5-fold decrease in nos. of Bifidobacterium and Faecalibacterium spp (P < .05); and, when present, a 4-fold lower av. no. of methanogens (3.50 × 107 vs 8.74 × 106 cells/g feces; P = .003). Correlation anal. of the microbial groups and IBS symptom scores indicated the involvement of several groups of Firmicutes and Proteobacteria in the pathogenesis of IBS. Conclusions: Global and deep mol. anal. of fecal samples indicates that patients with IBS have a different compn. of microbiota. This information might be used to develop better diagnostics and ultimately treatments for IBS.
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122Pittayanon, R.; Lau, J. T.; Yuan, Y.; Leontiadis, G. I.; Tse, F.; Surette, M.; Moayyedi, P. Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. Gastroenterology 2019, 157, 97– 108, DOI: 10.1053/j.gastro.2019.03.049122https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M%252FhtVaisg%253D%253D&md5=9c44fc6126c5738a4923952192240d91Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic ReviewPittayanon Rapat; Lau Jennifer T; Yuan Yuhong; Leontiadis Grigorios I; Tse Frances; Surette Michael; Moayyedi PaulGastroenterology (2019), 157 (1), 97-108 ISSN:.BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is common but difficult to treat. Altering the gut microbiota has been proposed as a strategy for treatment of IBS, but the association between the gut microbiome and IBS symptoms has not been well established. We performed a systematic review to explore evidence for this association. METHODS: We searched databases, including MEDLINE, EMBASE, Cochrane CDSR, and CENTRAL, through April 2, 2018 for case-control studies comparing the fecal or colon microbiomes of adult or pediatric patients with IBS with microbiomes of healthy individuals (controls). The primary outcome was differences in specific gut microbes between patients with IBS and controls. RESULTS: The search identified 2631 citations; 24 studies from 22 articles were included. Most studies evaluated adults presenting with various IBS subtypes. Family Enterobacteriaceae (phylum Proteobacteria), family Lactobacillaceae, and genus Bacteroides were increased in patients with IBS compared with controls, whereas uncultured Clostridiales I, genus Faecalibacterium (including Faecalibacterium prausnitzii), and genus Bifidobacterium were decreased in patients with IBS. The diversity of the microbiota was either decreased or not different in IBS patients compared with controls. More than 40% of included studies did not state whether cases and controls were comparable (did not describe sex and/or age characteristics). CONCLUSIONS: In a systematic review, we identified specific bacteria associated with microbiomes of patients with IBS vs controls. Studies are needed to determine whether these microbes are a product or cause of IBS.
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123El-Salhy, M.; Hatlebakk, J. G.; Gilja, O. H.; Bråthen Kristoffersen, A.; Hausken, T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut 2020, 69, 859– 867, DOI: 10.1136/gutjnl-2019-319630123https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVCht7vI&md5=5ff6c2ba597e8af3db30ac4569f6c021Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled studyEl-Salhy, Magdy; Hatlebakk, Jan Gunnar; Gilja, Odd Helge; Kristoffersen, Anja Braathen; Hausken, TrygveGut (2020), 69 (5), 859-867CODEN: GUTTAK; ISSN:0017-5749. (BMJ)Objective Faecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings. Design This randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a redn. in the IBS symptoms at 3 mo after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a redn. in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analyzed by 16S rRNA gene sequencing, at 1 mo following FMT. Results Responses occurred in 23.6%, 76.9% (p < 0.0001) and 89.1% (p < 00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, resp. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms. Conclusions FMT is an effective treatment for patients with IBS. Utilizing a well-defined donor with a normal DI and favorable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose.
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124Wilson, B.; Rossi, M.; Kanno, T.; Parkes, G. C.; Anderson, S.; Mason, A. J.; Irving, P. M.; Lomer, M. C.; Whelan, K. β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal Bifidobacteria. Am. J. Gastroenterol. 2020, 115, 906– 915, DOI: 10.14309/ajg.0000000000000641124https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38vpsVGgsA%253D%253D&md5=aa2615e105539ac6d3a069d39e76b492β-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal BifidobacteriaWilson Bridgette; Rossi Megan; Lomer Miranda C; Whelan Kevin; Wilson Bridgette; Lomer Miranda C; Kanno Tokuwa; Mason A James; Parkes Gareth C; Anderson Simon; Irving Peter MThe American journal of gastroenterology (2020), 115 (6), 906-915 ISSN:.INTRODUCTION: The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). β-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. METHODS: We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. RESULTS: At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). DISCUSSION: The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.
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125Vasant, D. H.; Paine, P. A.; Black, C. J.; Houghton, L. A.; Everitt, H. A.; Corsetti, M.; Agrawal, A.; Aziz, I.; Farmer, A. D.; Eugenicos, M. P. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021, 70, 1214– 1240, DOI: 10.1136/gutjnl-2021-324598125https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sblvVektg%253D%253D&md5=3d4f2e18c2008dea28e43666bd713126British Society of Gastroenterology guidelines on the management of irritable bowel syndromeVasant Dipesh H; Vasant Dipesh H; Paine Peter A; Paine Peter A; Black Christopher J; Ford Alexander C; Black Christopher J; Houghton Lesley A; Ford Alexander C; Houghton Lesley A; Everitt Hazel A; Corsetti Maura; Agrawal Anurag; Aziz Imran; Aziz Imran; Farmer Adam D; Farmer Adam D; Eugenicos Maria P; Moss-Morris Rona; Yiannakou YanGut (2021), 70 (7), 1214-1240 ISSN:.Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.
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126Moayyedi, P.; Andrews, C. N.; MacQueen, G.; Korownyk, C.; Marsiglio, M.; Graff, L.; Kvern, B.; Lazarescu, A.; Liu, L.; Paterson, W. G. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS). J. Can. Assoc Gastroenterol 2019, 2, 6– 29, DOI: 10.1093/jcag/gwy071126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mzmt1OnsA%253D%253D&md5=0774e7ab2ec3948ad8c141e21c61867aCanadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS)Moayyedi Paul; Sidani Sacha; Andrews Christopher N; MacQueen Glenda; Korownyk Christina; Marsiglio Megan; Graff Lesley; Kvern Brent; Lazarescu Adriana; Liu Louis; Paterson William G; Vanner StephenJournal of the Canadian Association of Gastroenterology (2019), 2 (1), 6-29 ISSN:.BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS. METHODS: A systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient. RESULTS: Consensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments. CONCLUSIONS: Patients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.
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127Fukudo, S.; Okumura, T.; Inamori, M.; Okuyama, Y.; Kanazawa, M.; Kamiya, T.; Sato, K.; Shiotani, A.; Naito, Y.; Fujikawa, Y. Evidence-based clinical practice guidelines for irritable bowel syndrome 2020. J. Gastroenterol. 2021, 56, 193– 217, DOI: 10.1007/s00535-020-01746-z127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srpsFajtg%253D%253D&md5=1e7734581ce8e2ac14b0c96312d3c01aEvidence-based clinical practice guidelines for irritable bowel syndrome 2020Fukudo Shin; Okumura Toshikatsu; Inamori Masahiko; Okuyama Yusuke; Kanazawa Motoyori; Kamiya Takeshi; Sato Ken; Shiotani Akiko; Naito Yuji; Fujikawa Yoshiko; Hokari Ryota; Masaoka Tastuhiro; Fujimoto Kazuma; Kaneko Hiroshi; Torii Akira; Matsueda Kei; Miwa Hiroto; Enomoto Nobuyuki; Shimosegawa Tooru; Koike Kazuhiko; Fukudo ShinJournal of gastroenterology (2021), 56 (3), 193-217 ISSN:.Managing irritable bowel syndrome (IBS) has attracted international attention because single-agent therapy rarely relieves bothersome symptoms for all patients. The Japanese Society of Gastroenterology (JSGE) published the first edition of evidence-based clinical practice guidelines for IBS in 2015. Much more evidence has accumulated since then, and new pharmacological agents and non-pharmacological methods have been developed. Here, we report the second edition of the JSGE-IBS guidelines comprising 41 questions including 12 background questions on epidemiology, pathophysiology, and diagnostic criteria, 26 clinical questions on diagnosis and treatment, and 3 questions on future research. For each question, statements with or without recommendations and/or evidence level are given and updated diagnostic and therapeutic algorithms are provided based on new evidence. Algorithms for diagnosis are requisite for patients with chronic abdominal pain or associated symptoms and/or abnormal bowel movement. Colonoscopy is indicated for patients with one or more alarm symptoms/signs, risk factors, and/or abnormal routine examination results. The diagnosis is based on the Rome IV criteria. Step 1 therapy consists of diet therapy, behavioral modification, and gut-targeted pharmacotherapy for 4 weeks. For non-responders, management proceeds to step 2 therapy, which includes a combination of different mechanistic gut-targeted agents and/or psychopharmacological agents and basic psychotherapy for 4 weeks. Step 3 therapy is for non-responders to step 2 and comprises a combination of gut-targeted pharmacotherapy, psychopharmacological treatments, and/or specific psychotherapy. These updated JSGE-IBS guidelines present best practice strategies for IBS patients in Japan and we believe these core strategies can be useful for IBS diagnosis and treatment globally.
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128Lacy, B. E.; Pimentel, M.; Brenner, D. M.; Chey, W. D.; Keefer, L. A.; Long, M. D.; Moshiree, B. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am. J. Gastroenterol. 2021, 116, 17, DOI: 10.14309/ajg.0000000000001036128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXnt1Grtrk%253D&md5=26264e26c18a80d33974d3dbdddf4303ACG clinical guideline: management of irritable bowel syndromeLacy, Brian E.; Pimentel, Mark; Brenner, Darren M.; Chey, William D.; Keefer, Laurie A.; Long, Millie D.; Moshiree, BahaAmerican Journal of Gastroenterology (2021), 116 (1), 17-44CODEN: AJGAAR; ISSN:1572-0241. (Wolters Kluwer)Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterol. clin. guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodol. Twenty-five clin. important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodol., we endorse the following: We suggest that a pos. diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serol. testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Addnl. statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.
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129Ford, A. C.; Harris, L. A.; Lacy, B. E.; Quigley, E. M. M.; Moayyedi, P. Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment. Pharmacol. Ther. 2018, 48, 1044– 1060, DOI: 10.1111/apt.15001129https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3czmslWmuw%253D%253D&md5=f74e29349f47d2004d956c06846f4691Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndromeFord Alexander C; Ford Alexander C; Harris Lucinda A; Lacy Brian E; Quigley Eamonn M M; Moayyedi PaulAlimentary pharmacology & therapeutics (2018), 48 (10), 1044-1060 ISSN:.BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology. AIM: To perform a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials (RCTs) recruiting adults with IBS, comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardised mean difference with a 95% CI. RESULTS: The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty-three RCTs of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non-constipated IBS patients, which was more effective than placebo (RR of symptoms persisting = 0.84; 95% CI 0.79-0.90). Adverse events were no more common with probiotics or antibiotics. CONCLUSIONS: Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non-constipated IBS.
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130Caruso, R.; Lo, B. C.; Núñez, G. Host-microbiota interactions in inflammatory bowel disease. Nat. Rev. Immunol. 2020, 20, 411– 426, DOI: 10.1038/s41577-019-0268-7130https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXislequ70%253D&md5=3ebd4c5a2950e065f9c578324d0643b5Host-microbiota interactions in inflammatory bowel diseaseCaruso, Roberta; Lo, Bernard C.; Nunez, GabrielNature Reviews Immunology (2020), 20 (7), 411-426CODEN: NRIABX; ISSN:1474-1733. (Nature Research)Abstr.: The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. The presence of large nos. of symbionts near the epithelial surface of the intestine poses an enormous challenge to the host because it must avoid the activation of harmful inflammatory responses to the microorganisms while preserving its ability to mount robust immune responses to invading pathogens. In patients with inflammatory bowel disease, there is a breakdown of the multiple strategies that the immune system has evolved to promote the sepn. between symbiotic microorganisms and the intestinal epithelium and the effective killing of penetrant microorganisms, while suppressing the activation of inappropriate T cell responses to resident microorganisms. Understanding the complex interactions between intestinal microorganisms and the host may provide crucial insight into the pathogenesis of inflammatory bowel disease as well as new avenues to prevent and treat the disease.
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131Federici, S.; Kredo-Russo, S.; Valdés-Mas, R.; Kviatcovsky, D.; Weinstock, E.; Matiuhin, Y.; Silberberg, Y.; Atarashi, K.; Furuichi, M.; Oka, A. Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation. Cell 2022, 185, 2879– 2898.e24, DOI: 10.1016/j.cell.2022.07.003131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitVChurfF&md5=e0fa16b8aea85b8df9c03a9e7ca246d8Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammationFederici, Sara; Kredo-Russo, Sharon; Valdes-Mas, Rafael; Kviatcovsky, Denise; Weinstock, Eyal; Matiuhin, Yulia; Silberberg, Yael; Atarashi, Koji; Furuichi, Munehiro; Oka, Akihiko; Liu, Bo; Fibelman, Morine; Weiner, Iddo Nadav; Khabra, Efrat; Cullin, Nyssa; Ben-Yishai, Noa; Inbar, Dana; Ben-David, Hava; Nicenboim, Julian; Kowalsman, Noga; Lieb, Wolfgang; Kario, Edith; Cohen, Tal; Geffen, Yael Friedman; Zelcbuch, Lior; Cohen, Ariel; Rappo, Urania; Gahali-Sass, Inbar; Golembo, Myriam; Lev, Vered; Dori-Bachash, Mally; Shapiro, Hagit; Moresi, Claudia; Cuevas-Sierra, Amanda; Mohapatra, Gayatree; Kern, Lara; Zheng, Danping; Nobs, Samuel Philip; Suez, Jotham; Stettner, Noa; Harmelin, Alon; Zak, Naomi; Puttagunta, Sailaja; Bassan, Merav; Honda, Kenya; Sokol, Harry; Bang, Corinna; Franke, Andre; Schramm, Christoph; Maharshak, Nitsan; Sartor, Ryan Balfour; Sorek, Rotem; Elinav, EranCell (Cambridge, MA, United States) (2022), 185 (16), 2879-2898.e24CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geog. distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly assocd. with disease exacerbation and severity. Transfer of clin. IBD-assocd. Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-assocd. Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.
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132Nagalingam, N. A.; Lynch, S. V. Role of the microbiota in inflammatory bowel diseases. Inflamm. Bowel Dis. 2012, 18, 968– 984, DOI: 10.1002/ibd.21866132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38zlvFehuw%253D%253D&md5=36eaa38f264de538590085654a704292Role of the microbiota in inflammatory bowel diseasesNagalingam Nabeetha A; Lynch Susan VInflammatory bowel diseases (2012), 18 (5), 968-84 ISSN:.Studying the role of the human microbiome as it relates to human health status has revolutionized our view of microbial community contributions to a large number of diseases, particularly chronic inflammatory disorders. The lower gastrointestinal (GI) tract houses trillions of microbial cells representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is not surprising, therefore, that many GI inflammatory diseases, including inflammatory bowel disease (IBD), are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Here we review current knowledge in the emerging field of human microbiome research as it relates to IBD, specifically focusing on Crohn's disease (CD) and ulcerative colitis (UC). We discuss bacteriotherapeutic efforts to restore GI microbial assemblage integrity via probiotic supplementation of IBD patients, and speculate on future directions for the field.
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133Barcenilla, A.; Pryde, S. E.; Martin, J. C.; Duncan, S. H.; Stewart, C. S.; Henderson, C.; Flint, H. J. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol. 2000, 66, 1654– 1661, DOI: 10.1128/AEM.66.4.1654-1661.2000133https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXisVWmu7g%253D&md5=98a4294d41eb8141fdda17b857791129Phylogenetic relationships of butyrate-producing bacteria from the human gutBarcenilla, Adela; Pryde, Susan E.; Martin, Jennifer C.; Duncan, Sylvia H.; Stewart, Colin S.; Henderson, Colin; Flint, Harry J.Applied and Environmental Microbiology (2000), 66 (4), 1654-1661CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)Butyrate is a preferred energy source for colonic epithelial cells and is thought to play an important role in maintaining colonic health in humans. In order to investigate the diversity and stability of butyrate-producing organisms of the colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly voided human fecal samples from 3 healthy individuals: an infant, an adult omnivore, and an adult vegetarian. A 2nd isolation was performed on the same 3 individuals 1 yr later. Of a total of 313 bacterial isolates, 74 produced more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism anal. The results indicate very little overlap between the predominant ribotypes of the 3 subjects; furthermore, the flora of each individual changed significantly between the 2 isolations. Complete sequences of 16S rDNAs were detd. for 24 representative strains and subjected to phylogenetic anal. Eighty percent of the butyrate-producing isolates fell within the XIVa cluster of gram-pos. bacteria as defined by M. D. Collins et al. and A. Willems et al., with the most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale, Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the butyrate-producing isolates were net acetate consumers during growth, suggesting that they employ the butyryl CoA-acetyl CoA transferase pathway for butyrate prodn. In contrast, only 1% of the 239 non-butyrate-producing isolates consumed acetate.
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134Halfvarson, J.; Brislawn, C. J.; Lamendella, R.; Vázquez-Baeza, Y.; Walters, W. A.; Bramer, L. M.; D’Amato, M.; Bonfiglio, F.; McDonald, D.; Gonzalez, A. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat. Microbiol 2017, 2, 17004, DOI: 10.1038/nmicrobiol.2017.4134https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkvFyqt7s%253D&md5=31d20fb740e9e065969614896c2cca3aDynamics of the human gut microbiome in inflammatory bowel diseaseHalfvarson, Jonas; Brislawn, Colin J.; Lamendella, Regina; Vazquez-Baeza, Yoshiki; Walters, William A.; Bramer, Lisa M.; D'Amato, Mauro; Bonfiglio, Ferdinando; McDonald, Daniel; Gonzalez, Antonio; McClure, Erin E.; Dunklebarger, Mitchell F.; Knight, Rob; Jansson, Janet K.Nature Microbiology (2017), 2 (1), 17004CODEN: NMAICH; ISSN:2058-5276. (Nature Publishing Group)Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The etiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behavior of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, esp. subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between obsd. dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.
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135Mottawea, W.; Chiang, C.-K.; Mühlbauer, M.; Starr, A. E.; Butcher, J.; Abujamel, T.; Deeke, S. A.; Brandel, A.; Zhou, H.; Shokralla, S. Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease. Nat. Commun. 2016, 7, 13419, DOI: 10.1038/ncomms13419135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitFSns77P&md5=700643e7cd70e13bb35625e955a3bce7Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's diseaseMottawea, Walid; Chiang, Cheng-Kang; Muhlbauer, Marcus; Starr, Amanda E.; Butcher, James; Abujamel, Turki; Deeke, Shelley A.; Brandel, Annette; Zhou, Hu; Shokralla, Shadi; Hajibabaei, Mehrdad; Singleton, Ruth; Benchimol, Eric I.; Jobin, Christian; Mack, David R.; Figeys, Daniel; Stintzi, AlainNature Communications (2016), 7 (), 13419CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Intestinal microbial dysbiosis is assocd. with Crohn's disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation anal. reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host-microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.
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136Marchesi, J. R.; Holmes, E.; Khan, F.; Kochhar, S.; Scanlan, P.; Shanahan, F.; Wilson, I. D.; Wang, Y. Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J. Proteome Res. 2007, 6, 546– 551, DOI: 10.1021/pr060470d136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhs12gtQ%253D%253D&md5=af033580ca436e4056e7262110730ac1Rapid and Noninvasive Metabonomic Characterization of Inflammatory Bowel DiseaseMarchesi, Julian R.; Holmes, Elaine; Khan, Fatima; Kochhar, Sunil; Scanlan, Pauline; Shanahan, Fergus; Wilson, Ian D.; Wang, YulanJournal of Proteome Research (2007), 6 (2), 546-551CODEN: JPROBS; ISSN:1535-3893. (American Chemical Society)Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have a major impact on the health of individuals and populations. Accurate diagnosis of inflammatory bowel disease (IBD) at an early stage, and correct differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is important for optimum treatment and prognosis. The authors present here the first characterization of fecal exts. obtained from patients with CD and UC by employing a noninvasive metabonomics approach, which combines high resoln. 1H NMR spectroscopy and multivariate pattern recognition techniques. The fecal exts. of both CD and UC patients were characterized by reduced levels of butyrate, acetate, methylamine, and trimethylamine in comparison with a control population, suggesting changes in the gut microbial community. Also, elevated quantities of amino acids were present in the feces from both disease groups, implying malabsorption caused by the inflammatory disease or an element of protein losing enteropathy. Metabolic differences in fecal profiles were more marked in the CD group in comparison with the control group, indicating that the inflammation caused by CD is more extensive in comparison with UC and involves the whole intestine. Furthermore, glycerol resonances were a dominant feature of fecal spectra from patients with CD but were present in much lower intensity in the control and UC groups. This work illustrates the potential of metabonomics to generate novel noninvasive diagnostics for gastrointestinal diseases and may further our understanding of disease mechanisms.
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137Van Immerseel, F.; Ducatelle, R.; De Vos, M.; Boon, N.; Van De Wiele, T.; Verbeke, K.; Rutgeerts, P.; Sas, B.; Louis, P.; Flint, H. J. Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease. J. Med. Microbiol. 2010, 59, 141– 143, DOI: 10.1099/jmm.0.017541-0137https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c%252FktVGltQ%253D%253D&md5=c0e88381cc635630a1a3d0362ffeb7c2Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel diseaseVan Immerseel Filip; Ducatelle Richard; De Vos Martine; Boon Nico; Van De Wiele Tom; Verbeke Kristin; Rutgeerts Paul; Sas Benedikt; Louis Petra; Flint Harry JJournal of medical microbiology (2010), 59 (Pt 2), 141-143 ISSN:.There is no expanded citation for this reference.
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138Miquel, S.; Martín, R.; Rossi, O.; Bermúdez-Humarán, L. G.; Chatel, J. M.; Sokol, H.; Thomas, M.; Wells, J. M.; Langella, P. Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol. 2013, 16, 255– 261, DOI: 10.1016/j.mib.2013.06.003138https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKqsr7K&md5=9d63ee3ca46ee654075ae06da77ef52fFaecalibacterium prausnitzii and human intestinal healthMiquel, S.; Martin, R.; Rossi, O.; Bermudez-Humaran, L. G.; Chatel, J. M.; Sokol, H.; Thomas, M.; Wells, J. M.; Langella, P.Current Opinion in Microbiology (2013), 16 (3), 255-261CODEN: COMIF7; ISSN:1369-5274. (Elsevier Ltd.)A review. Faecalibacterium prausnitzii is the most abundant bacterium in the human intestinal microbiota of healthy adults, representing more than 5% of the total bacterial population. Over the past five years, an increasing no. of studies have clearly described the importance of this highly metabolically active commensal bacterium as a component of the healthy human microbiota. Changes in the abundance of F. prausnitzii have been linked to dysbiosis in several human disorders. Administration of F. prausnitzii strain A2-165 and its culture supernatant have been shown to protect against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Here, we discuss the role of F. prausnitzii in balancing immunity in the intestine and the mechanisms involved.
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139Tamanai-Shacoori, Z.; Smida, I.; Bousarghin, L.; Loreal, O.; Meuric, V.; Fong, S. B.; Bonnaure-Mallet, M.; Jolivet-Gougeon, A. Roseburia spp.: a marker of health?. Future Microbiol. 2017, 12, 157– 170, DOI: 10.2217/fmb-2016-0130139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslWhtbY%253D&md5=9d57c7df0d1668e2bb44e05afd2e45edRoseburia spp.: a marker of health?Tamanai-Shacoori, Zohreh; Smida, Imen; Bousarghin, Latifa; Loreal, Olivier; Meuric, Vincent; Fong, Shao Bing; Bonnaure-Mallet, Martine; Jolivet-Gougeon, AnneFuture Microbiology (2017), 12 (2), 157-170CODEN: FMUIAR; ISSN:1746-0913. (Future Medicine Ltd.)A review. The genus Roseburia consists of obligate Gram-pos. anaerobic bacteria that are slightly curved, rod-shaped and motile by means of multiple subterminal flagella. It includes five species: Roseburia intestinalis, R. hominis, R. inulinivorans, R. faecis and R. cecicola. Gut Roseburia spp. metabolize dietary components that stimulate their proliferation and metabolic activities. They are part of commensal bacteria producing short-chain fatty acids, esp. butyrate, affecting colonic motility, immunity maintenance and anti-inflammatory properties. Modification in Roseburia spp. representation may affect various metabolic pathways and is assocd. with several diseases (including irritable bowel syndrome, obesity, Type 2 diabetes, nervous system conditions and allergies). Roseburia spp. could also serve as biomarkers for symptomatic pathologies (e.g., gallstone formation) or as probiotics for restoration of beneficial flora.
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140Li, Y.; Xia, S.; Jiang, X.; Feng, C.; Gong, S.; Ma, J.; Fang, Z.; Yin, J.; Yin, Y. Gut Microbiota and Diarrhea: An Updated Review. Microbiology 2021, 11, 625210, DOI: 10.3389/fcimb.2021.625210140https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sbpt1aluw%253D%253D&md5=efb07829392f2514713f0ede26ef97f8Gut Microbiota and Diarrhea: An Updated ReviewLi Yunxia; Xia Siting; Jiang Xiaohan; Feng Can; Gong Saiming; Ma Jie; Yin Jie; Yin Yulong; Fang Zhengfeng; Yin YulongFrontiers in cellular and infection microbiology (2021), 11 (), 625210 ISSN:.Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.
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141Hodges, K.; Gill, R. Infectious diarrhea: Cellular and molecular mechanisms. Gut Microbes 2010, 1, 4– 21, DOI: 10.4161/gmic.1.1.11036141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sboslOhtA%253D%253D&md5=b0992f6a97ff50dff635deea9065d231Infectious diarrhea: Cellular and molecular mechanismsHodges Kim; Gill RavinderGut microbes (2010), 1 (1), 4-21 ISSN:.Diarrhea caused by enteric infections is a major factor in morbidity and mortality worldwide. An estimated 2-4 billion episodes of infectious diarrhea occur each year and are especially prevalent in infants. This review highlights the cellular and molecular mechanisms underlying diarrhea associated with the three classes of infectious agents, i.e., bacteria, viruses and parasites. Several bacterial pathogens have been chosen as model organisms, including Vibrio cholerae as a classical example of secretory diarrhea, Clostridium difficile and Shigella species as agents of inflammatory diarrhea and selected strains of pathogenic Escherichia coli (E. coli) to discuss the recent advances in alteration of epithelial ion absorption. Many of the recent studies addressing epithelial ion transport and barrier function have been carried out using viruses and parasites. Here, we focus on the rapidly developing field of viral diarrhea including rotavirus, norovirus and astrovirus infections. Finally we discuss Giardia lamblia and Entamoeba histolytica as examples of parasitic diarrhea. Parasites have a greater complexity than the other pathogens and are capable of creating molecules similar to those produced by the host, such as serotonin and PGE(2). The underlying mechanisms of infectious diarrhea discussed include alterations in ion transport and tight junctions as well as the virulence factors, which alter these processes either through direct effects or indirectly through inflammation and neurotransmitters.
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142Levine, M. M. Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J. Infect. Dis. 1987, 155, 377– 389, DOI: 10.1093/infdis/155.3.377142https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL2s7htVylsw%253D%253D&md5=28f3bb6db9138f13a131fadf174fe710Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherentLevine M MThe Journal of infectious diseases (1987), 155 (3), 377-89 ISSN:0022-1899.There are four major categories of diarrheagenic Escherichia coli: enterotoxigenic (a major cause of travelers' diarrhea and infant diarrhea in less-developed countries), enteroinvasive (a cause of dysentery), enteropathogenic (an important cause of infant diarrhea), and enterohemorrhagic (a cause of hemorrhagic colitis and hemolytic uremic syndrome). Besides manifesting distinct clinical patterns, these categories of E. coli differ in their epidemiology and pathogenesis and in their O:H serotypes. Common features (albeit distinct for each category) include plasmid-encoded virulence properties, characteristic interactions with intestinal mucosa, and elaboration of various types of enterotoxins or cytotoxins. A less-well-defined fifth category of diarrheagenic E. coli is that of enteroadherent E. coli, so far identifiable only by their pattern of adherence to Hep-2 cells in tissue culture.
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143Gallo, A.; Passaro, G.; Gasbarrini, A.; Landolfi, R.; Montalto, M. Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate. World J. Gastroenterol. 2016, 22, 7186– 7202, DOI: 10.3748/wjg.v22.i32.7186143https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2svgtVCqtw%253D%253D&md5=976dc72a198f8a598627eb8a347d3c7cModulation of microbiota as treatment for intestinal inflammatory disorders: An uptodateGallo Antonella; Passaro Giovanna; Gasbarrini Antonio; Landolfi Raffaele; Montalto MassimoWorld journal of gastroenterology (2016), 22 (32), 7186-202 ISSN:.Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.
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144Bron, P. A.; Kleerebezem, M.; Brummer, R. J.; Cani, P. D.; Mercenier, A.; MacDonald, T. T.; Garcia-Ródenas, C. L.; Wells, J. M. Can probiotics modulate human disease by impacting intestinal barrier function?. Br. J. Nutr. 2017, 117, 93– 107, DOI: 10.1017/S0007114516004037144https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvVyks74%253D&md5=73dd9acb7e2cf433fbcfb1a3d706d8e5Can probiotics modulate human disease by impacting intestinal barrier function?Bron, Peter A.; Kleerebezem, Michiel; Brummer, Robert-Jan; Cani, Patrice D.; Mercenier, Annick; MacDonald, Thomas T.; Garcia-Rodenas, Clara L.; Wells, Jerry M.British Journal of Nutrition (2017), 117 (1), 93-107CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chem. and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major etiol. factors assocd. with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in which in vitro cell lines, animal models and clin. trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the redn. of gastrointestinal disease symptoms.
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145Zhang, S.; Wang, R.; Li, D.; Zhao, L.; Zhu, L. Role of gut microbiota in functional constipation. Gastroenterol. Rep. 2021, 9, 392– 401, DOI: 10.1093/gastro/goab035145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cjos1eitw%253D%253D&md5=d9df2a9e9bd37ff2920138061a0d473eRole of gut microbiota in functional constipationZhang Shengsheng; Wang Ruixin; Li Danyan; Zhao Luqing; Zhu LixinGastroenterology report (2021), 9 (5), 392-401 ISSN:2052-0034.Functional constipation (FC) is common, yet the etiology is not clear. Accumulating evidence suggests an association between FC and abnormal gut microbiota. The relationship between the gut microbiota and the gut transit is likely bidirectional. This review summarizes the current evidence regarding the impact of gut microbiota on the pathogenesis of FC. By modulating the colonic motility, secretion, and absorption, gut microbiota may contribute to the development of FC through microbial metabolic activities involving bile acids, short-chain fatty acids, 5-hydroxytryptamine, and methane. In support of the key roles of the gut microbiota in FC, treatment with probiotics, prebiotics, synbiotics, and traditional Chinese medicine often result in compositional and functional changes in the gut microbiota. Further studies on the pathogenesis of FC and the therapeutic mechanism of microecological agents will provide a knowledge base for better management of FC.
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146Zoppi, G.; Cinquetti, M.; Luciano, A.; Benini, A.; Muner, A.; Bertazzoni Minelli, E. The intestinal ecosystem in chronic functional constipation. Acta Paediatr. 1998, 87, 836– 841, DOI: 10.1111/j.1651-2227.1998.tb01547.x146https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1cvgsFKgtQ%253D%253D&md5=bb92c7610207657d2e9c5dad125d53c2The intestinal ecosystem in chronic functional constipationZoppi G; Cinquetti M; Luciano A; Benini A; Muner A; Bertazzoni Minelli EActa paediatrica (Oslo, Norway : 1992) (1998), 87 (8), 836-41 ISSN:0803-5253.Chronic functional constipation is common in infants, and the bacterial composition of stools in this condition is not known. The study aims were to: (i) investigate the composition of the intestinal ecosystem in chronic functional constipation; (ii) establish whether the addition of the water-holding agent calcium polycarbophil to the diet induces an improvement in constipation; and (iii) determine the composition of the intestinal ecosystem after the use of this agent. In total, 42 children (20F, 22M; mean age: 8.6 +/- 2.9 y) were studied. Twenty-eight children with functional chronic constipation without anatomical disorders were treated double-blind in random sequence for 1 month with an oral preparation of calcium polycarbophil (0.62 g/twice daily) or placebo. Intestinal flora composition was evaluated by standard microbiological methods and biochemical assays on faecal samples collected before and after treatment. Fourteen healthy children were studied as controls. The results show that (i) the constipated children presented a significant increase in clostridia and bifidobacteria in faeces compared to healthy subjects--different species of clostridia and enterobacteriaceae were frequently isolated; no generalized overgrowth was observed; Clostridia outnumbered bacteroides and E. coli mean counts by 2-3log, while bacteroides and E. coli counts were similar (5-6 log10/g fresh faeces); these intestinal disturbances could be defined as a dysbiosis, i.e. a quantitative alteration in the relative proportions of certain intestinal bacterial species. (ii) Clinical resolution of constipation was achieved only in 43% of treated children and an improvement in 21% (one bowel movement every 2 d). (iii) Calcium polycarbophil treatment induced no significant changes in the composition of the intestinal ecosystem, nor in blood chemistry parameters.
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147Khalif, I. L.; Quigley, E. M.; Konovitch, E. A.; Maximova, I. D. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig. Liver Dis. 2005, 37, 838– 849, DOI: 10.1016/j.dld.2005.06.008147https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MrmsFCntQ%253D%253D&md5=7b2a49da0e98a1645fa10ad657392e4cAlterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipationKhalif I L; Quigley E M M; Konovitch E A; Maximova I DDigestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (2005), 37 (11), 838-49 ISSN:1590-8658.BACKGROUND: Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. AIM: To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. METHODS: Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. RESULTS: Ovalbumin concentrations, in serum, were higher in constipated patients (28.2+/-4.1 ng/ml versus 1.0+/-0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. CONCLUSION: Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation.
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148Kim, S. E.; Choi, S. C.; Park, K. S.; Park, M. I.; Shin, J. E.; Lee, T. H.; Jung, K. W.; Koo, H. S.; Myung, S. J. Change of Fecal Flora and Effectiveness of the Short-term VSL#3 Probiotic Treatment in Patients With Functional Constipation. J. Neurogastroenterol. Motil. 2015, 21, 111– 120, DOI: 10.5056/jnm14048148https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MvhslOltA%253D%253D&md5=bfd9824ac1d168c6ba1dbc0aa8172459Change of Fecal Flora and Effectiveness of the Short-term VSL#3 Probiotic Treatment in Patients With Functional ConstipationKim Seong-Eun; Choi Suck Chei; Park Kyung Sik; Park Moo In; Shin Jeong Eun; Lee Tae Hee; Jung Kee Wook; Myung Seung-Jae; Koo Hoon SupJournal of neurogastroenterology and motility (2015), 21 (1), 111-20 ISSN:2093-0879.BACKGROUND/AIMS: We investigated gut flora characteristics in patients with functional constipation (FC) and influences of short-term treatment with VSL#3 probiotic on flora and symptom improvement. METHODS: Thirty patients fulfilling Rome III criteria for FC and 30 controls were enrolled. Fecal samples were obtained before and after VSL#3 intake (one sachet twice daily for 2 weeks) and flora were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Symptom changes were also investigated. RESULTS: The fold differences in Bifidobacterium and Bacteroides species were significantly lower in feces from FC, compared to in controls (P = 0.030 and P = 0.021). After taking VSL#3, the fold differences in Lactobacillus, Bifidobacterium and Bacteroides species increased in controls (P = 0.022, P = 0.018, and P = 0.076), but not in FC. Mean Bristol scores and complete spontaneous bowel movements (CSBMs)/week increased significantly in FC after ingesting VSL#3 (both P < 0.001). Relief of subjective CSBM frequency, stool consistency and abdominal bloating were reported in 70%, 60%, and 47% of patients. After VSL#3 cessation, 44.4% of patients with symptom improvement experienced constipation recurrence mostly within one month. CONCLUSIONS: Bifidobacterium and Bacteroides species might be quantitatively altered in FC. A short-term VSL#3 treatment can improve clinical symptoms of FC. Further studies are needed to investigate VSL#3's additional effects beyond altering gut flora to allevate constipation.
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149Zhu, L.; Liu, W.; Alkhouri, R.; Baker, R. D.; Bard, J. E.; Quigley, E. M.; Baker, S. S. Structural changes in the gut microbiome of constipated patients. Physiol. Genomics 2014, 46, 679– 686, DOI: 10.1152/physiolgenomics.00082.2014149https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFGqu7%252FO&md5=8b1c0286b36bab313ee6443b9d83bde3Structural changes in the gut microbiome of constipated patientsZhu, Lixin; Liu, Wensheng; Alkhouri, Razan; Baker, Robert D.; Bard, Jonathan E.; Quigley, Eamonn M.; Baker, Susan S.Physiological Genomics (2014), 46 (18), 679-686CODEN: PHGEFP; ISSN:1094-8341. (American Physiological Society)Previous studies using culture-based methods suggested an assocn. between constipation and altered abundance of certain taxa of the colonic microbiome. We aim to examine the global changes in gut microbial compn. of constipated patients. A cross-sectional pilot study using 16S rRNA gene pyrosequencing was performed to compare stool microbial compn. of eight constipated patients and 14 nonconstipated controls. Only obese children were enrolled so that the microbiome features assocd. with constipation would not be obscured by those assocd. with obesity. The sequencing reads were processed by QIIME for quant. anal. of the microbial compn. at genus and above levels. Dietary intake for all the individuals was assessed by dietary recalls and a food frequency questionnaire. The ecol. diversities of fecal microbiome of the constipated patients differed from those of the controls. Significantly decreased abundance in Prevotella and increased representation in several genera of Firmicutes were obsd. in constipated patients compared with controls. The conventional probiotic genera Lactobacillus and Bifidobacteria were not decreased in the microbiomes of the constipated patients. These alterations in the fecal microbiome of constipated patients suggested that a novel probiotic treatment including certain Prevotella strains may be more effective than conventional probiotic products incorporating Lactobacillus or Bifidobacterium species. While it is possible that the obsd. changes in the microbiome in constipated subjects are a consequence of a low-fiber diet, these changes also predict a different pattern of bacterial fermn. end-products, such as increased butyrate prodn., which may contribute to pathogenesis of constipation.
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150Mancabelli, L.; Milani, C.; Lugli, G. A.; Turroni, F.; Mangifesta, M.; Viappiani, A.; Ticinesi, A.; Nouvenne, A.; Meschi, T.; van Sinderen, D. Unveiling the gut microbiota composition and functionality associated with constipation through metagenomic analyses. Sci. Rep. 2017, 7, 9879, DOI: 10.1038/s41598-017-10663-w150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cbislGnsw%253D%253D&md5=1285e7fb794c5d616cac6450d7923cbeUnveiling the gut microbiota composition and functionality associated with constipation through metagenomic analysesMancabelli Leonardo; Milani Christian; Lugli Gabriele Andrea; Turroni Francesca; Mangifesta Marta; Ventura Marco; Mangifesta Marta; Viappiani Alice; Ticinesi Andrea; Nouvenne Antonio; Meschi Tiziana; van Sinderen DouweScientific reports (2017), 7 (1), 9879 ISSN:.Functional constipation (FC) is a gastrointestinal disorder with a high prevalence among the general population. The precise causes of FC are still unknown and are most likely multifactorial. Growing evidence indicates that alterations of gut microbiota composition contribute to constipation symptoms. Nevertheless, many discrepancies exist in literature and no clear link between FC and gut microbiota composition has as yet been identified. In this study, we performed 16 S rRNA-based microbial profiling analysis of 147 stool samples from 68 FC individuals and compared their microbial profiles with those of 79 healthy subjects (HS). Notably, the gut microbiota of FC individuals was shown to be depleted of members belonging to Bacteroides, Roseburia and Coprococcus 3. Furthermore, the metabolic capabilities of the gut microbiomes of five FC and five HS individuals were evaluated through shotgun metagenomics using a MiSeq platform, indicating that HS are enriched in pathways involved in carbohydrate, fatty acid and lipid metabolism as compared to FC. In contrast, the microbiomes corresponding to FC were shown to exhibit high abundance of genes involved in hydrogen production, methanogenesis and glycerol degradation. The identified differences in bacterial composition and metabolic capabilities may play an important role in development of FC symptoms.
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151Naseer, M.; Poola, S.; Uraz, S.; Tahan, V. Therapeutic Effects of Prebiotics on Constipation: A Schematic Review. Curr. Clin. Pharmacol. 2020, 15, 207– 215, DOI: 10.2174/1574884715666200212125035151https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB387ht1ShsA%253D%253D&md5=333bbe352c02460c64cc165b31ad482bTherapeutic Effects of Prebiotics on Constipation: A Schematic ReviewNaseer Maliha; Poola Shiva; Uraz Suleyman; Tahan VeyselCurrent clinical pharmacology (2020), 15 (3), 207-215 ISSN:.Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics to play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested, stimulating the bacteria. There are a variety of prebiotics; however, there exists only a handful of studies that describe their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfil the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation were used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear.
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152Zhao, Y.; Yu, Y. B. Intestinal microbiota and chronic constipation. SpringerPlus 2016, 5, 1130, DOI: 10.1186/s40064-016-2821-1152https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3msFOgsA%253D%253D&md5=c5af5044bf440bc6084a4e44e7fb775bIntestinal microbiota and chronic constipationZhao Ying; Yu Yan-BoSpringerPlus (2016), 5 (1), 1130 ISSN:2193-1801.Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose aetiology and pathophysiology remains poorly understood and is most likely multifactorial. Differences in the composition of the intestinal microbiota have been demonstrated when constipated patients and healthy controls have been compared. Growing evidence indicates that alterations of intestinal microbiota may contribute to constipation and constipation-related symptoms. The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, and perform many important health-promoting functions. The intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, prevents growth of pathogenic bacteria and produces a great variety of biologically important compounds. In this review, we will summarize the current evidence supporting roles of the intestinal microbiota in the pathogenesis and management of chronic constipation. The discussion will shed light on the novel mechanisms of intestinal microbiota and gut function interactions, which is invaluable in ultimately developing new therapeutic tools for the treatment of chronic constipation.
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153Wang, J. K.; Yao, S. K. Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation. Evid. Based Complement. Alternat. Med. 2021, 2021, 5560310, DOI: 10.1155/2021/5560310153https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cnls1Khtg%253D%253D&md5=e92d8375b6e14e6d3f100cd1a98f292dRoles of Gut Microbiota and Metabolites in Pathogenesis of Functional ConstipationWang Jun-Ke; Yao Shu-KunEvidence-based complementary and alternative medicine : eCAM (2021), 2021 (), 5560310 ISSN:1741-427X.Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.
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154Rao, S. S.; Rattanakovit, K.; Patcharatrakul, T. Diagnosis and management of chronic constipation in adults. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 295– 305, DOI: 10.1038/nrgastro.2016.53154https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XlvVahsLk%253D&md5=91b31cc77cb456a5854799580e9fbb52Diagnosis and management of chronic constipation in adultsRao, Satish S. C.; Rattanakovit, Kulthep; Patcharatrakul, TanisaNature Reviews Gastroenterology & Hepatology (2016), 13 (5), 295-305CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)Constipation is a heterogeneous, polysymptomatic, multifactorial disease. Acute or transient constipation can be due to changes in diet, travel or stress, and secondary constipation can result from drug treatment, neurol. or metabolic conditions or, rarely, colon cancer. A diagnosis of primary chronic constipation is made after exclusion of secondary causes of constipation and encompasses several overlapping subtypes. Slow-transit constipation is characterized by prolonged colonic transit in the absence of pelvic floor dysfunction. This subtype of constipation can be identified using either the radio-opaque marker test or wireless motility capsule test, and is best treated with laxatives such as polyethylene glycol or newer agents such as linaclotide or lubiprostone. If unsuccessful, subspecialist referral should be considered. Dyssynergic defecation results from impaired coordination of rectoanal and pelvic floor muscles, and causes difficulty with defecation. The condition can be identified using anorectal manometry and balloon expulsion tests and is best managed with biofeedback therapy. Opioid-induced constipation is an emerging entity, and several drugs including naloxegol, methylnaltrexone and lubiprostone are approved for its treatment. In this Review, we provide an overview of the burden and pathophysiol. of chronic constipation, as well as a detailed discussion of the available diagnostic tools and treatment options.
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155Moloney, R. D.; Desbonnet, L.; Clarke, G.; Dinan, T. G.; Cryan, J. F. The microbiome: stress, health and disease. Mamm. Genome 2014, 25, 49– 74, DOI: 10.1007/s00335-013-9488-5155https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXisVCjurs%253D&md5=9a35ad22dd20c688980e752910dab5f5The microbiome: stress, health and diseaseMoloney, Rachel D.; Desbonnet, Lieve; Clarke, Gerard; Dinan, Timothy G.; Cryan, John F.Mammalian Genome (2014), 25 (1-2), 49-74CODEN: MAMGEC; ISSN:0938-8990. (Springer)A review. Bacterial colonization of the gut plays a major role in postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Individually, these systems have been implicated in the neuropathol. of many CNS disorders and collectively they form an important bidirectional pathway of communication between the microbiota and the brain in health and disease. Regulation of the microbiome-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the CNS and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome-brain-gut axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.
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156Mayer, E. A.; Tillisch, K.; Gupta, A. Gut/brain axis and the microbiota. J. Clin. Invest. 2015, 125, 926– 938, DOI: 10.1172/JCI76304156https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MrmtFamsw%253D%253D&md5=5d580088b116af24ebfcd56dc65685c1Gut/brain axis and the microbiotaMayer Emeran A; Tillisch Kirsten; Gupta ArpanaThe Journal of clinical investigation (2015), 125 (3), 926-38 ISSN:.Tremendous progress has been made in characterizing the bidirectional interactions between the central nervous system, the enteric nervous system, and the gastrointestinal tract. A series of provocative preclinical studies have suggested a prominent role for the gut microbiota in these gut-brain interactions. Based on studies using rodents raised in a germ-free environment, the gut microbiota appears to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems. Additionally, microbiota perturbations by probiotics and antibiotics exert modulatory effects on some of these measures in adult animals. Current evidence suggests that multiple mechanisms, including endocrine and neurocrine pathways, may be involved in gut microbiota-to-brain signaling and that the brain can in turn alter microbial composition and behavior via the autonomic nervous system. Limited information is available on how these findings may translate to healthy humans or to disease states involving the brain or the gut/brain axis. Future research needs to focus on confirming that the rodent findings are translatable to human physiology and to diseases such as irritable bowel syndrome, autism, anxiety, depression, and Parkinson's disease.
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157Maldonado-Contreras, A.; Noel, S. E.; Ward, D. V.; Velez, M.; Mangano, K. M. Associations between Diet, the Gut Microbiome, and Short-Chain Fatty Acid Production among Older Caribbean Latino Adults. J. Acad. Nutr. Diet. 2020, 120, 2047– 2060.e46, DOI: 10.1016/j.jand.2020.04.018157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38flslGluw%253D%253D&md5=9bc2c76ab72b39cc1244e29a64cae3caAssociations between Diet, the Gut Microbiome, and Short-Chain Fatty Acid Production among Older Caribbean Latino AdultsMaldonado-Contreras Ana; Noel Sabrina E; Ward Doyle V; Velez Martha; Mangano Kelsey MJournal of the Academy of Nutrition and Dietetics (2020), 120 (12), 2047-2060.e6 ISSN:2212-2672.BACKGROUND: Caribbean Latino adults have disproportionately high prevalence of chronic disease; however, underlying mechanisms are unknown. Unique gut microbiome profiles and relation to dietary quality may underlie health disparities. OBJECTIVES: To examine the dietary quality of an underrepresented group of Caribbean Latino older adults with high prevalence of chronic disease; characterize gut microbiome profiles in this cohort; determine associations between dietary quality, gut microbiome composition, and short-chain fatty acid (SCFA) production; examine associations of clinical factors (body mass index, type 2 diabetes [T2D] status, and laxative use) with gut microbiome composition. DESIGN: The study design was cross-sectional. PARTICIPANTS/SETTING: Recruitment and interviews occurred at the Senior Center in Lawrence, MA, from September 2016-September 2017. A total of 20 adults aged ≥50 years, self-identified of Caribbean Latino origin, without use of antibiotics in 6 months or intestinal surgery were included in the study. EXPOSURE AND OUTCOME MEASURES: Diet was assessed by two, 24-hour recalls and dietary quality was calculated using the Healthy Eating Index 2015 and the Mediterranean Diet Score. The gut microbiome was assessed by 16S rRNA sequencing and fecal SCFA content. Anthropometrics (ie, weight and height) were measured by a trained interviewer, and self-reported laxative use, and other self-report health outcomes (ie, T2D status) were assessed by questionnaire. STATISTICAL ANALYSES: Faith Phylogenetic Diversity (alpha diversity) and unique fraction metric, or UniFrac (beta diversity) and nonphylogenetic metrics, including Shannon diversity index (alpha diversity) were calculated. Spearman correlations and group comparisons using Kruskal-Wallis test between alpha diversity indexes and nutrient intakes were calculated. Patterns in the microbiome were estimated using a partitioning around medoids with estimation of number of clusters, with optimum average silhouette width. Log odds were calculated to compare predefined nutrients and diet score components between microbiome clusters using multivariable logistic regression, controlling for age and sex. Pearson correlation was used to relate SCFA fecal content to individual nutrients and diet indexes. Final models were additionally adjusted for laxative use. Differences in lifestyle factors by gut microbiome cluster were tested by Fisher's exact test. RESULTS: Generally, there was poor alignment of participant's diets to either the Mediterranean Diet score or Healthy Eating Index 2015. Range in the Healthy Eating Index 2015 was 36 to 90, where only 5% (n=1) of the sample showed high adherence to the Dietary Guidelines for Americans. Mediterranean Diet scores suggested low conformance with a Mediterranean eating pattern (score range=2 to 8, where 45% scored ≤3 [poor adherence]). The gut microbiome separated into two clusters by difference in a single bacterial taxon: Prevotella copri (P copri) (permutational multivariate analysis of variance [PERMANOVA] R(2)=0.576, ADONIS function P=0.001). Significantly lower P copri abundance was observed in cluster 1 compared with cluster 2 (Mann-Whitney P<0.0001). Samples in the P copri dominated cluster 2 showed significantly lower alpha diversity compared with P copri depleted cluster 1 (Shannon diversity index P=0.01). Individuals in the P copri dominated cluster showed a trend toward higher 18:3 α-linolenic fatty acid intakes (P=0.09). Percentage of energy from total fat intake was significantly, positively correlated with fecal acetate (r=0.46; P=0.04), butyrate (r=0.50; P=0.03) and propionate (r=0.52; P=0.02). Associations between dietary intake and composition of the gut microbiome were attenuated by self-report recent laxative use. Individuals with T2D exhibited a significantly greater abundance of the Enterobacteriales (P=0.01) and a trend toward lower fecal content of butyric acid compared to subjects without T2D (P=0.08). Significant beta diversity differences were observed by weight (Mantel P<0.003) and body mass index (Mantel P<0.07). CONCLUSIONS: Two unique microbiome profiles, identified by abundance of P copri, were identified among Caribbean Latino adults. Microbiome profiles and SCFA content were associated with diet, T2D, and lifestyle. Further research is needed to determine the role of P copri and SCFA production in the risk for chronic disease and associated lifestyle predictors.
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158Zhang, H.; Chen, Y.; Wang, Z.; Xie, G.; Liu, M.; Yuan, B.; Chai, H.; Wang, W.; Cheng, P. Implications of Gut Microbiota in Neurodegenerative Diseases. Front. Immunol. 2022, 13, 785644, DOI: 10.3389/fimmu.2022.785644158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtFOkt7fM&md5=68c103031718c0c55e2498bd4b781b40Implications of gut microbiota in neurodegenerative diseasesZhang, Haoming; Chen, Yijia; Wang, Zifan; Xie, Gaijie; Liu, Mingming; Yuan, Boyu; Chai, Hongxia; Wang, Wei; Cheng, PingFrontiers in Immunology (2022), 13 (), 785644CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)A review. The morbidity assocd. with neurodegenerative diseases (NDs) is increasing, posing a threat to the mental and phys. quality of life of humans. The crucial effect of microbiota on brain physiol. processes is mediated through a bidirectional interaction, termed as the gut-brain axis (GBA), which is being investigated in studies. Many clin. and lab. trials have indicated the importance of microbiota in the development of NDs via various microbial mols. that transmit from the gut to the brain across the GBA or nervous system. In this review, we summarize the implications of gut microbiota in ND, which will be beneficial for understanding the etiol. and progression of NDs that may in turn help in developing ND interventions and clin. treatments for these diseases.
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159Roy Sarkar, S.; Banerjee, S. Gut microbiota in neurodegenerative disorders. J. Neuroimmunol. 2019, 328, 98– 104, DOI: 10.1016/j.jneuroim.2019.01.004159https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXht1egsro%253D&md5=cbe8cf0d5ab1219eee5e557cd6340014Gut microbiota in neurodegenerative disordersRoy Sarkar, Suparna; Banerjee, SugatoJournal of Neuroimmunology (2019), 328 (), 98-104CODEN: JNRIDW; ISSN:0165-5728. (Elsevier B.V.)Gut dysbiosis, a primary factor behind various gastrointestinal disorders may also augment lipopolysaccharides, pro-inflammatory cytokines, T helper cells and monocytes causing increased intestinal and BBB permeability via microbiota-gut-brain axis. Consequentially, accumulation of misfolded proteins, axonal damage and neuronal demyelination sets in, thus facilitating the pathogenesis of neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. Studies revealed that intake of probiotics may help in the integrity of intestinal and BBB thus ameliorating the above neurodegenerative disorders. This review summarizes the current understanding of the role of gut microbiota in neurodegenerative disorders and possible intervention strategies.
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160Caspani, G.; Kennedy, S.; Foster, J. A.; Swann, J. Gut microbial metabolites in depression: understanding the biochemical mechanisms. Microbial cell (Graz, Austria) 2019, 6, 454– 481, DOI: 10.15698/mic2019.10.693160https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MjhtFWhsA%253D%253D&md5=74a02883592b6c0009887f5ffdb711edGut microbial metabolites in depression: understanding the biochemical mechanismsCaspani Giorgia; Swann Jonathan; Kennedy Sidney; Kennedy Sidney; Kennedy Sidney; Kennedy Sidney; Foster Jane AMicrobial cell (Graz, Austria) (2019), 6 (10), 454-481 ISSN:2311-2638.Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
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161Roubalová, R.; Procházková, P.; Papežová, H.; Smitka, K.; Bilej, M.; Tlaskalová-Hogenová, H. Anorexia nervosa: Gut microbiota-immune-brain interactions. Clin. Nutr. 2020, 39, 676– 684, DOI: 10.1016/j.clnu.2019.03.023161https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmtlWltb8%253D&md5=53f56ee5d87562a45c58636f1e4e5c1dAnorexia nervosa: Gut microbiota-immune-brain interactionsRoubalova, Radka; Prochazkova, Petra; Papezova, Hana; Smitka, Kvido; Bilej, Martin; Tlaskalova-Hogenova, HelenaClinical Nutrition (2020), 39 (3), 676-684CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)A review. Anorexia nervosa is a psychiatric disorder defined by an extremely low body wt., a devastating fear of wt. gain, and body image disturbance, however the etiopathogenesis remains unclear. The objective of the article is to provide a comprehensive review on the potential role of gut microbiota in pathogenesis of anorexia nervosa. Recent advances in sequencing techniques used for microbial detection revealed that this disease is assocd. with disruption of the compn. of normal gut microbiota (dysbiosis), manifested by low microbial diversity and taxonomic differences as compared to healthy individuals. Microorganisms present in the gut represent a part of the so called "microbiota-gut-brain" axis that affect the central nervous system and thus human behavior via the prodn. of various neuroactive compds. In addn., cells of the immune system are equipped with receptors for these neuroactive substances. Microbiota of the intestinal system also represent a very important antigenic source. These antigens can mimic some host neuropeptides and neurohormones and thus trigger the prodn. of autoantibodies which cross-react with these compds. The levels and affinities of these antibodies are thought to be assocd. with neuropsychiatric conditions including anxiety, depression, and eating and sleep disorders. The study of microbiota function in diseases could bring new insights to the pathogenetic mechanisms.
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162Zhang, L.; Wang, Y.; Xiayu, X.; Shi, C.; Chen, W.; Song, N.; Fu, X.; Zhou, R.; Xu, Y. F.; Huang, L. Altered Gut Microbiota in a Mouse Model of Alzheimer’s Disease. J. Alzheimers Dis. 2017, 60, 1241– 1257, DOI: 10.3233/JAD-170020162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7htFOnuw%253D%253D&md5=fe7ee394cfc39a0938651c94753ff3f3Altered Gut Microbiota in a Mouse Model of Alzheimer's DiseaseZhang Ling; Wang Ying; Xiayu Xia; Shi Changhua; Chen Wei; Song Nan; Fu Xinjing; Zhou Rui; Xu Yan-Feng; Huang Lan; Zhu Hua; Han Yunlin; Qin Chuan; Zhang Ling; Wang Ying; Xiayu Xia; Shi Changhua; Chen Wei; Song Nan; Fu Xinjing; Zhou Rui; Xu Yan-Feng; Huang Lan; Zhu Hua; Han Yunlin; Qin ChuanJournal of Alzheimer's disease : JAD (2017), 60 (4), 1241-1257 ISSN:.The topic of gut microbiota is currently attracting considerable interest as a potential factor in Alzheimer's disease (AD). However, the extent and time course of alterations in the gut microbiota, and their effects on AD pathology remain uncertain. Herein, we compared the fecal microbiomes and fecal short chain fatty acid composition (SCFAs) between wild-type and AD model mice at different ages under strictly controlled specific pathogen free conditions, and also conducted microscopic investigations of intestinal structures. Our results showed that the microbiota composition and diversity were perturbed and the level of SCFAs was reduced in AD mice, predicting alterations in more than 30 metabolic pathways, which may be associated with amyloid deposition and ultrastructural abnormalities in AD mouse intestine. These findings indicate that AD pathology might not only affect brain function directly, but also exacerbate cognitive deficits through reducing the level of SCFAs via alterations of gut microbiota induced by intestinal amyloid deposition. Our data may support a role of gut microbiota, and suggest a novel route for therapeutic intervention in AD.
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163Wang, L.; Christophersen, C. T.; Sorich, M. J.; Gerber, J. P.; Angley, M. T.; Conlon, M. A. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig. Dis. Sci. 2012, 57, 2096– 2102, DOI: 10.1007/s10620-012-2167-7163https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFWhs7fI&md5=70b345cd24f3b076e8a74081fb98afc1Elevated Fecal Short Chain Fatty Acid and Ammonia Concentrations in Children with Autism Spectrum DisorderWang, Lv; Christophersen, Claus Thagaard; Sorich, Michael Joseph; Gerber, Jacobus Petrus; Angley, Manya Therese; Conlon, Michael AllanDigestive Diseases and Sciences (2012), 57 (8), 2096-2102CODEN: DDSCDJ; ISSN:0163-2116. (Springer)Background and Aim: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder where a high frequency of gastrointestinal disturbance (e.g., constipation and diarrhea) is reported. As large bowel fermn. products can have beneficial or detrimental effects on health, these were measured in feces of children with and without ASD to examine whether there is an underlying disturbance in fermn. processes in the disorder. Methods: Fecal samples (48 h) were collected from children with ASD (n = 23), and without ASD (n = 31) of similar age. Concns. of short chain fatty acids, phenols and ammonia were measured. Results: Fecal total short chain fatty acid concns. were significantly higher in children with ASD compared to controls (136.6 ± 8.7 vs. 111.1 ± 6.6 mmol/kg). Moreover, when concns. of fecal acetic, butyric, isobutyric, valeric, isovaleric and caproic acids were measured, all were significantly higher in children with ASD compared with controls except for caproic acid. The concn. of fecal ammonia was also significantly greater in ASD participants than controls (42.7 ± 3.3 vs. 32.3 ± 1.9 mmol/kg). Fecal phenol levels and pH did not differ between groups. Macronutrient intake, as detd. from dietary records kept by caregivers, also did not differ significantly between study groups. Conclusions: Our results suggest fermn. processes or utilization of fermn. products may be altered in children with ASD compared to children without ASD.
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164Galland, L. The gut microbiome and the brain. J. Med. Food 2014, 17, 1261– 1272, DOI: 10.1089/jmf.2014.7000164https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitVCisLfF&md5=25f538028791b1083d830713915d4c50The Gut Microbiome and the BrainGalland, LeoJournal of Medicinal Food (2014), 17 (12), 1261-1272CODEN: JMFOFJ; ISSN:1096-620X. (Mary Ann Liebert, Inc.)A review. The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clin. and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurol. manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.
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165Heneka, M. T.; Carson, M. J.; El Khoury, J.; Landreth, G. E.; Brosseron, F.; Feinstein, D. L.; Jacobs, A. H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R. M. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015, 14, 388– 405, DOI: 10.1016/S1474-4422(15)70016-5165https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvVSksrw%253D&md5=df821845eaf19cc6c6a9c6fdf1f805d6Neuroinflammation in Alzheimer's diseaseHeneka, Michael T.; Carson, Monica J.; El Khoury, Joseph; Landreth, Gary E.; Brosseron, Frederic; Feinstein, Douglas L.; Jacobs, Andreas H.; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M.; Herrup, Karl; Frautschy, Sally A.; Finsen, Bente; Brown, Guy C.; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C.; Town, Terrence; Morgan, Dave; Shinohara, Mari L.; Perry, V. Hugh; Holmes, Clive; Bazan, Nicolas G.; Brooks, David J.; Hunot, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.Lancet Neurology (2015), 14 (4), 388-405CODEN: LNAEAM; ISSN:1474-4422. (Elsevier Ltd.)A review. Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunol. mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterized by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide anal. suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunol. processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
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166Ransohoff, R. M. How neuroinflammation contributes to neurodegeneration. Science 2016, 353, 777– 783, DOI: 10.1126/science.aag2590166https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlCju73I&md5=eaa975b2ac5903376d8ac10fed7b0820How neuroinflammation contributes to neurodegenerationRansohoff, Richard M.Science (Washington, DC, United States) (2016), 353 (6301), 777-783CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal lobar dementia are among the most pressing problems of developed societies with aging populations. Neurons carry out essential functions such as signal transmission and network integration in the central nervous system and are the main targets of neurodegenerative disease. In this Review, I address how the neuron's environment also contributes to neurodegeneration. Maintaining an optimal milieu for neuronal function rests with supportive cells termed glia and the blood-brain barrier. Accumulating evidence suggests that neurodegeneration occurs in part because the environment is affected during disease in a cascade of processes collectively termed neuroinflammation. These observations indicate that therapies targeting glial cells might provide benefit for those afflicted by neurodegenerative disorders.
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167Karlsson, O.; Roman, E.; Berg, A. L.; Brittebo, E. B. Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period. Behav. Brain Res. 2011, 219, 310– 320, DOI: 10.1016/j.bbr.2011.01.056167https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjs1yrtrw%253D&md5=e396db542acd6ea46235a8af414949ecEarly hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal periodKarlsson, Oskar; Roman, Erika; Berg, Anna-Lena; Brittebo, Eva B.Behavioural Brain Research (2011), 219 (2), 310-320CODEN: BBREDI; ISSN:0166-4328. (Elsevier B.V.)We have reported previously that exposure to the cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) during the neonatal period causes cognitive impairments in adult rats. The aim of this study was to investigate the long-term effects of neonatal BMAA exposure on learning and memory mechanisms and to identify early morphol. changes in the neonatal brain. BMAA was injected s.c. in rat pups on postnatal days 9-10. BMAA (50 and 200 mg/kg) caused distinct deficits in spatial learning and memory in adult animals but no morphol. changes. No impairment of recognition memory was detected, suggesting that neonatal exposure to BMAA preferentially affects neuronal systems that are important for spatial tasks. Histopathol. examn. revealed early neuronal cell death as detd. by TUNEL staining in the hippocampus 24 h after a high dose (600 mg/kg) of BMAA whereas no changes were obsd. at lower doses (50 and 200 mg/kg). In addn., there was a low degree of neuronal cell death in the retrosplenial and cingulate cortices, areas that are also important for cognitive function. Taken together, these results indicate that BMAA is a developmental neurotoxin inducing long-term changes in cognitive function. The risk posed by BMAA as a potential human neurotoxin merits further consideration, particularly if the proposed biomagnifications in the food chain are confirmed.
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168Nunes-Costa, D.; Magalhães, J. D.; G-Fernandes, M.; Cardoso, S. M.; Empadinhas, N. Microbial BMAA and the Pathway for Parkinson’s Disease Neurodegeneration. Front. Aging Neurosci. 2020, 12, 26, DOI: 10.3389/fnagi.2020.00026168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1OlsrnP&md5=2430730210ba86f0235baecc1bc46bedMicrobial BMAA and the pathway for Parkinson's disease neurodegenerationNunes-Costa, Daniela; Magalhaes, Joao Duarte; G-Fernandes, Maria; Cardoso, Sandra Morais; Empadinhas, NunoFrontiers in Aging Neuroscience (2020), 12 (), 26CODEN: FANRC5; ISSN:1663-4365. (Frontiers Media S.A.)The neurotoxin β-N-methylamino-L-alanine (BMAA) is a natural non-proteinogenic diamino acid produced by several species of both prokaryotic (cyanobacteria) and eukaryotic (diatoms and dinoflagellates) microorganisms. BMAA has been shown to biomagnify through the food chain in some ecosystems, accumulating for example in seafood such as shellfish and fish, common dietary sources of BMAA whose ingestion may have possible neuronal consequences. In addn. to its excitotoxic potential, BMAA has been implicated in protein misfolding and aggregation, inhibition of specific enzymes and neuroinflammation, all hallmark features of neurodegenerative diseases. However, the exact mol. mechanisms of neurotoxicity remain to be elucidated in detail. Although BMAA is commonly detected in its free form, complex BMAA-contg. mols. have also been identified such as the paenilamicins, produced by an insect gut bacterial pathogen. On the other hand, prodn. of BMAA or BMAA-contg. mols. by members of the human gut microbiota, for example by non-photosynthetic cyanobacteria, the Melainabacteria, remains only hypothetical. In any case, should BMAA reach the gut it may interact with cells of the mucosal immune system and neurons of the enteric nervous system (ENS) and possibly target the mitochondria. Here, we review the available evidence and hint on possible mechanisms by which chronic exposure to dietary sources of this microbial neurotoxin may drive protein misfolding and mitochondrial dysfunction with concomitant activation of innate immune responses, chronic low-grade gut inflammation, and ultimately the neurodegenerative features obsd. across the gut-brain axis in Parkinson's disease (PD).
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169Braak, H.; Rüb, U.; Gai, W. P.; Del Tredici, K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J. Neural Transm (Vienna) 2003, 110, 517– 536, DOI: 10.1007/s00702-002-0808-2169https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3s3gt1GltQ%253D%253D&md5=23ec33b5feb7fdb9b6959fc8d02f8205Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogenBraak H; Rub U; Gai W P; Del Tredici KJournal of neural transmission (Vienna, Austria : 1996) (2003), 110 (5), 517-36 ISSN:0300-9564.The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.
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170Wallen, Z. D.; Demirkan, A.; Twa, G.; Cohen, G.; Dean, M. N.; Standaert, D. G.; Sampson, T. R.; Payami, H. Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Nat. Commun. 2022, 13, 6958, DOI: 10.1038/s41467-022-34667-x170https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFWks7bP&md5=a13a8d0c27f697c48e0b43b90594ed2dMetagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanismsWallen, Zachary D.; Demirkan, Ayse; Twa, Guy; Cohen, Gwendolyn; Dean, Marissa N.; Standaert, David G.; Sampson, Timothy R.; Payami, HaydehNature Communications (2022), 13 (1), 6958CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resoln., using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide assocn. studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease assocn., network anal. to identify polymicrobial clusters, and functional profiling. Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-assocd. species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of mols. that induce alpha-synuclein pathol., and over-prodn. of toxicants; with the redn. in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were obsd. in exptl. models; reconcile and resolve human PD microbiome literature; and provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.
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171Vogt, N. M.; Kerby, R. L.; Dill-McFarland, K. A.; Harding, S. J.; Merluzzi, A. P.; Johnson, S. C.; Carlsson, C. M.; Asthana, S.; Zetterberg, H.; Blennow, K. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 2017, 7, 13537, DOI: 10.1038/s41598-017-13601-y171https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7is1CgsA%253D%253D&md5=d577a8c8a7b9ed5e83e5f2d9c3699ea0Gut microbiome alterations in Alzheimer's diseaseVogt Nicholas M; Harding Sandra J; Merluzzi Andrew P; Johnson Sterling C; Carlsson Cynthia M; Asthana Sanjay; Bendlin Barbara B; Kerby Robert L; Dill-McFarland Kimberly A; Rey Federico E; Johnson Sterling C; Carlsson Cynthia M; Asthana Sanjay; Johnson Sterling C; Carlsson Cynthia M; Bendlin Barbara B; Zetterberg Henrik; Blennow Kaj; Zetterberg Henrik; Blennow Kaj; Zetterberg Henrik; Zetterberg HenrikScientific reports (2017), 7 (1), 13537 ISSN:.Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
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172Zhuang, Z. Q.; Shen, L. L.; Li, W. W.; Fu, X.; Zeng, F.; Gui, L.; Lü, Y.; Cai, M.; Zhu, C.; Tan, Y. L. Gut Microbiota is Altered in Patients with Alzheimer’s Disease. J. Alzheimers Dis. 2018, 63, 1337– 1346, DOI: 10.3233/JAD-180176172https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MfjtVequg%253D%253D&md5=5d0d6c93eb43549ab5fa4c5c5ca3149eGut Microbiota is Altered in Patients with Alzheimer's DiseaseZhuang Zhen-Qian; Shen Lin-Lin; Li Wei-Wei; Zeng Fan; Zhu Chi; Li Hui-Yun; Zhu Jie; Zhou Hua-Dong; Bu Xian-Le; Wang Yan-Jiang; Fu Xue; Lu Yang; Gui Li; Cai Min; Tan Yin-Ling; Zheng PengJournal of Alzheimer's disease : JAD (2018), 63 (4), 1337-1346 ISSN:.Previous studies suggest that gut microbiota is associated with neuropsychiatric disorders, such as Parkinson's disease, amyotrophic lateral sclerosis, and depression. However, whether the composition and diversity of gut microbiota is altered in patients with Alzheimer's disease (AD) remains largely unknown. In the present study, we collected fecal samples from 43 AD patients and 43 age- and gender-matched cognitively normal controls. 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. The composition of gut microbiota was different between the two groups. Several bacteria taxa in AD patients were different from those in controls at taxonomic levels, such as Bacteroides, Actinobacteria, Ruminococcus, Lachnospiraceae, and Selenomonadales. Our findings suggest that gut microbiota is altered in AD patients and may be involved in the pathogenesis of AD.
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173Manderino, L.; Carroll, I.; Azcarate-Peril, M. A.; Rochette, A.; Heinberg, L.; Peat, C.; Steffen, K.; Mitchell, J.; Gunstad, J. Preliminary Evidence for an Association Between the Composition of the Gut Microbiome and Cognitive Function in Neurologically Healthy Older Adults. J. Int. Neuropsychol. Soc. 2017, 23, 700– 705, DOI: 10.1017/S1355617717000492173https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjgvFOhsA%253D%253D&md5=57f1fd37f2b71297b444efc7eb1cbe1dPreliminary Evidence for an Association Between the Composition of the Gut Microbiome and Cognitive Function in Neurologically Healthy Older AdultsManderino Lisa; Rochette Amber; Gunstad John; Carroll Ian; Azcarate-Peril M Andrea; Heinberg Leslie; Peat Christine; Steffen Kristine; Mitchell JamesJournal of the International Neuropsychological Society : JINS (2017), 23 (8), 700-705 ISSN:.OBJECTIVES: Dysbiosis of the gut microbiome is implicated in numerous human health conditions. Animal studies have linked microbiome disruption to changes in cognitive functioning, although no study has examined this possibility in neurologically healthy older adults. METHODS: Participants were 43 community-dwelling older adults (50-85 years) that completed a brief cognitive test battery and provided stool samples for gut microbiome sequencing. Participants performing≥1 SD below normative performance on two or more tests were compared to persons with one or fewer impaired scores. RESULTS: Mann Whitney U tests revealed different distributions of Bacteroidetes (p=.01), Firmicutes (p=.02), Proteobacteria (p=.04), and Verrucomicrobia (p=.003) between Intact and Impaired groups. These phyla were significantly correlated with cognitive test performances, particularly Verrucomicrobia and attention/executive function measures. CONCLUSIONS: The current findings suggest that composition of the gut microbiome is associated with cognitive test performance in neurologically healthy older adults. Future studies are needed to confirm these findings and explore possible mechanisms. (JINS, 2017, 23, 700-705).
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174Barbosa, R. S. D.; Vieira-Coelho, M. A. Probiotics and prebiotics: focus on psychiatric disorders - a systematic review. Nutr. Rev. 2020, 78, 437– 450, DOI: 10.1093/nutrit/nuz080174https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MfjsVajug%253D%253D&md5=5a4a8957e335389e7ab8be37cd83546eProbiotics and prebiotics: focus on psychiatric disorders - a systematic reviewBarbosa Renata S D; Vieira-Coelho Maria A; Vieira-Coelho Maria ANutrition reviews (2020), 78 (6), 437-450 ISSN:.CONTEXT: The gut-brain axis and microbial dysbiosis may play a role in psychiatric diseases. In this view, the gut microbiota has been considered a potential therapeutic target using probiotics and prebiotics. OBJECTIVE: This systematic review aims to find the existing clinical evidence that may justify the use of probiotics or prebiotics in psychiatric patients. DATA SOURCES: PRISMA guidelines were followed for a systematic literature review of randomized controlled trials that assessed the effect of prebiotics or probiotics in patients diagnosed with a classified psychiatric disorder. DATA EXTRACTION: From a total of 212 studies screened, 11 were included in the final systematic review. Quality assessment of the included trials was assessed by the Jadad scale. RESULTS: Probiotics seem to offer some benefit in major depressive disorder and Alzheimer's disease. One study showed that probiotics reduced rehospitalization in patients with acute mania. In autism spectrum disorders, the results were controversial; however a single study found that early administration of probiotics showed a preventive role. No benefits were found for patients with schizophrenia. In most studies, no major adverse effects were reported. CONCLUSIONS: Although recent findings in specific psychiatric disorders are encouraging, the use of prebiotics and probiotics in clinical practice stills lacks sufficiently robust evidence.
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175Ansari, F.; Pourjafar, H.; Tabrizi, A.; Homayouni, A. The Effects of Probiotics and Prebiotics on Mental Disorders: A Review on Depression, Anxiety, Alzheimer, and Autism Spectrum Disorders. Curr. Pharm. Biotechnol. 2020, 21, 555– 565, DOI: 10.2174/1389201021666200107113812175https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhslamsLrM&md5=9a728e9f22e2be662a4f20b3a96504ebThe effects of probiotics and prebiotics on mental disorders: a review on depression, anxiety, alzheimer, and autism spectrum disordersAnsari, Fereshteh; Pourjafar, Hadi; Tabrizi, Aydin; Homayouni, AzizCurrent Pharmaceutical Biotechnology (2020), 21 (7), 555-565CODEN: CPBUBP; ISSN:1389-2010. (Bentham Science Publishers Ltd.)A review. Background: Probiotics and their nutrient sources (prebiotics) have been shown to have pos. effects on different organs of the host. The idea of their potential benefits on Central Nervous Systems (CNS) and the incidence of Anxiety, Schizophrenia, Alzheimer, Depression, Autism, and other mental disorders has proposed a new category of medicines called "psychobiotic". Objective: In the current review, we present valuable insights into the complicated interactions between the GI microbiota (esp. in the colon), brain, immune and central nervous systems and provide a summary of the main findings of the effects of pro- and prebiotics on important mental disorders from the potential mechanisms of action to their application in clin. practice. Methods: The full text of potentially eligible studies was retrieved and assessed in detail by the reviewers. Results: The results of the provided evidence suggest that probiotic and prebiotics might improve mental function via several mechanisms. The beneficial effects of their application in Depression, Anxiety, Alzheimer and autism spectrum diseases have also been supported in clin. studies. Conclusion: Pro and prebiotics can improve mental health and psychol. function and can be offered as new medicines for common mental disorders, however, more clin. studies are necessary to conduct regarding the clin. significance of the effects and their bioequivalence or superiority against current treatments.
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176Messaoudi, M.; Lalonde, R.; Violle, N.; Javelot, H.; Desor, D.; Nejdi, A.; Bisson, J. F.; Rougeot, C.; Pichelin, M.; Cazaubiel, M. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr. 2011, 105, 755– 764, DOI: 10.1017/S0007114510004319176https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXitVOjsbo%253D&md5=ed9d1f4a7e88bad6f4a0d39c9e190f52Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjectsMessaoudi, Michael; Lalonde, Robert; Violle, Nicolas; Javelot, Herve; Desor, Didier; Nejdi, Amine; Bisson, Jean-Francois; Rougeot, Catherine; Pichelin, Matthieu; Cazaubiel, Murielle; Cazaubiel, Jean-MarcBritish Journal of Nutrition (2011), 105 (5), 755-764CODEN: BJNUAV; ISSN:0007-1145. (Cambridge University Press)In a previous clin. study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychol. distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclin. study, rats were daily administered PF for 2 wk and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clin. trial, volunteers participated in a double-blind, placebo-controlled, randomized parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behavior in rats (P < 0.05) and alleviated psychol. distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0.05; somatization, P < 0.05; depression, P < 0.05; and anger-hostility, P < 0.05), the HADS (HADS global score, P < 0.05; and HADS-anxiety, P < 0.06), and by the CCL (problem solving, P < 0.05) and the UFC level (P < 0.05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychol. effects in healthy human volunteers.
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177Akbari, E.; Asemi, Z.; Daneshvar Kakhaki, R.; Bahmani, F.; Kouchaki, E.; Tamtaji, O. R.; Hamidi, G. A.; Salami, M. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Front. Aging Neurosci. 2016, 8, 256, DOI: 10.3389/fnagi.2016.00256177https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtV2isbjK&md5=564df5ccf68fedfde448510e4790165cEffect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trialAkbari, Elmira; Asemi, Zatollah; Kakhaki, Reza Daneshvar; Bahmani, Fereshteh; Kouchaki, Ebrahim; Tamtaji, Omid Reza; Hamidi, Gholam Ali; Salami, MahmoudFrontiers in Aging Neuroscience (2016), 8 (), 256/1-256/8CODEN: FANRC5; ISSN:1663-4365. (Frontiers Media S.A.)Alzheimer's disease (AD) is assocd. with severe cognitive impairments as well as some metabolic defects. Scant studies in animal models indicate a link between probiotics and cognitive function. This randomized, double-blind, and controlled clin. trial was conducted among 60 AD patients to assess the effects of probiotic supplementation on cognitive function and metabolic status. The patients were randomly divided into two groups (n = 30 in each group) treating with either milk (control group) or a mixt. of probiotics (probiotic group). The probiotic supplemented group took 200 mL/day probiotic milk contg. Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 109 CFU/g for each) for 12 wk. Mini-mental state examn. (MMSE) score was recorded in all subjects before and after the treatment. Pre- and post-treatment fasting blood samples were obtained to det. the related markers. After 12 wk intervention, compared with the control group (-5.03% ± 3.00), the probiotic treated (+27.90% ± 8.07) patients showed a significant improvement in the MMSE score (P < 0.001). In addn., changes in plasma malondialdehyde (-22.01% ± 4.84 vs. +2.67% ± 3.86 μmol/L, P < 0.001), serum high-sensitivity C-reactive protein (-17.61% ± 3.70 vs. +45.26% ± 3.50 μg/mL, P < 0.001), homeostasis model of assessment-estd. insulin resistance (+28.84% ± 13.34 vs. +76.95% ± 24.60, P = 0.002), Beta cell function (+3.45% ± 10.91 vs. +75.62% ± 23.18, P = 0.001), serum triglycerides (-20.29% ± 4.49 vs. -0.16% ± 5.24 mg/dL, P = 0.003), and quant. insulin sensitivity check index (-1.83 ± 1.26 vs. -4.66 ± 1.70, P = 0.006) in the probiotic group were significantly varied compared to the control group. We found that the probiotic treatment had no considerable effect on other biomarkers of oxidative stress and inflammation, fasting plasma glucose, and other lipid profiles. Overall, the current study demonstrated that probiotic consumption for 12 wk pos. affects cognitive function and some metabolic statuses in the AD patients.
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178Nimgampalle, M.; Kuna, Y. Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s Disease induced Albino Rats. J. Clin. Diagn. Res. 2017, 11, Kc01– kc05, DOI: 10.7860/JCDR/2017/26106.10428There is no corresponding record for this reference.
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179Tamtaji, O. R.; Taghizadeh, M.; Daneshvar Kakhaki, R.; Kouchaki, E.; Bahmani, F.; Borzabadi, S.; Oryan, S.; Mafi, A.; Asemi, Z. Clinical and metabolic response to probiotic administration in people with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Clin. Nutr. 2019, 38, 1031– 1035, DOI: 10.1016/j.clnu.2018.05.018179https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFSgtr%252FP&md5=d1eeb5dea9fc4cabb4821be9e80c24f8Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trialTamtaji, Omid Reza; Taghizadeh, Mohsen; Daneshvar Kakhaki, Reza; Kouchaki, Ebrahim; Bahmani, Fereshteh; Borzabadi, Shokoofeh; Oryan, Shahrbanoo; Mafi, Alireza; Asemi, ZatollahClinical Nutrition (2019), 38 (3), 1031-1035CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)The investigation was done to assess the impacts of probiotic supplementation on movement and metabolic parameters in individuals with Parkinson's disease (PD).The study is randomized, double-blind, placebo-controlled clin. trial, which was done in sixty people with PD. Individuals were randomly divided into two groups in order to take either 8 × 109 CFU/day probiotic or placebo (n = 30 each group) that lasted 12 wk. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was recorded at pre- and post-intervention.Compared with the placebo, consuming probiotic decreased MDS-UPDRS (-4.8 ± 12.5 vs. +3.8 ± 13.0, P = 0.01). Probiotic supplementation also reduced high-sensitivity C-reactive protein (-1.6 ± 2.5 vs. +0.1 ± 0.3 mg/L, P < 0.001) and malondialdehyde (-0.2 ± 0.3 vs. +0.1 ± 0.3μmol/L, P = 0.006), and enhanced glutathione levels (+40.1 ± 81.5 vs. -12.1 ± 41.7μmol/L, P = 0.03) in comparison with the placebo. Addnl., probiotic consumption resulted in a statistically significant redn. in insulin levels (-2.1 ± 3.4 vs. +1.5 ± 5.1μIU/mL, P = 0.002) and insulin resistance (-0.5 ± 0.9 vs. +0.4 ± 1.2, P = 0.002), and a statistically significant rise in insulin sensitivity (+0.01 ± 0.02 vs. -0.006 ± 0.02, P = 0.01) in comparison with the placebo. Probiotic intake had no any significant impact on other metabolic profiles.Our study evidenced that 12 wk of probiotic consumption by individuals with PD had useful impacts on MDS-UPDRS and few metabolic profiles. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017082434497N4.
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180Frazier, K.; Chang, E. B. Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism. Trends Endocrinol Metab 2020, 31, 25– 36, DOI: 10.1016/j.tem.2019.08.013180https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslyqsbbO&md5=d1a714522940bc6ae225f017a09c51e1Intersection of the Gut Microbiome and Circadian Rhythms in MetabolismFrazier, Katya; Chang, Eugene B.Trends in Endocrinology and Metabolism (2020), 31 (1), 25-36CODEN: TENME4; ISSN:1043-2760. (Elsevier Ltd.)A review. The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiol. and metab. However, the mechanisms that underlie these observations remain largely unknown. Recent findings have implicated microbially derived mediators as potential signals between the gut microbiome and host circadian clocks; two specific mediators are discussed in this review: short-chain fatty acids (SCFAs) and bile acids (BAs). Key gaps in knowledge and major challenges that remain in the circadian and microbiome fields are also discussed, including animal vs. human models and the need for precise timed sample collection.
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181Gutierrez Lopez, D. E.; Lashinger, L. M.; Weinstock, G. M.; Bray, M. S. Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet. Cell Metab. 2021, 33, 873– 887, DOI: 10.1016/j.cmet.2021.03.015181https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXnslGitbY%253D&md5=55edf2c55d7b551bd0c74828f2caf50aCircadian rhythms and the gut microbiome synchronize the host metabolic response to dietGutierrez Lopez, Diana E.; Lashinger, Laura M.; Weinstock, George M.; Bray, Molly S.Cell Metabolism (2021), 33 (5), 873-887CODEN: CMEEB5; ISSN:1550-4131. (Elsevier Inc.)A review. The mol. circadian clock and symbiotic host-microbe relationships both evolved as mechanisms that enhance metabolic responses to environmental challenges. The gut microbiome benefits the host by breaking down diet-derived nutrients indigestible by the host and generating microbiota-derived metabolites that support host metab. Similarly, cellular circadian clocks optimize organismal physiol. to the environment by influencing the timing and coordination of metabolic processes. Host-microbe interactions are influenced by dietary quality and timing, as well as daily light/dark cycles that entrain circadian rhythms in the host. Together, the gut microbiome and the mol. circadian clock play a coordinated role in neural processing, metab., adipogenesis, inflammation, and disease initiation and progression. This examines the bidirectional interactions between the circadian clock, gut microbiota, and host metabolic systems and their effects on obesity and energy homeostasis. Directions for future research and the development of therapies that leverage these systems to address metabolic disease are highlighted.
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182Leng, Y.; Musiek, E. S.; Hu, K.; Cappuccio, F. P.; Yaffe, K. Association between circadian rhythms and neurodegenerative diseases. Lancet Neurol. 2019, 18, 307– 318, DOI: 10.1016/S1474-4422(18)30461-7182https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cflsFSnsg%253D%253D&md5=0816f7dd88b07bfa85b4b0f0f704c695Association between circadian rhythms and neurodegenerative diseasesLeng Yue; Musiek Erik S; Hu Kun; Cappuccio Francesco P; Yaffe KristineThe Lancet. Neurology (2019), 18 (3), 307-318 ISSN:.Dysfunction in 24-h circadian rhythms is a common occurrence in ageing adults; however, circadian rhythm disruptions are more severe in people with age-related neurodegenerative diseases, including Alzheimer's disease and related dementias, and Parkinson's disease. Manifestations of circadian rhythm disruptions differ according to the type and severity of neurodegenerative disease and, for some patients, occur before the onset of typical clinical symptoms of neurodegeneration. Evidence from preliminary studies suggest that circadian rhythm disruptions, in addition to being a symptom of neurodegeneration, might also be a potential risk factor for developing Alzheimer's disease and related dementias, and Parkinson's disease, although large, longitudinal studies are needed to confirm this relationship. The mechanistic link between circadian rhythms and neurodegeneration is still not fully understood, although proposed underlying pathways include alterations of protein homoeostasis and immune and inflammatory function. While preliminary clinical studies are promising, more studies of circadian rhythm disruptions and its mechanisms are required. Furthermore, clinical trials are needed to determine whether circadian interventions could prevent or delay the onset of neurodegenerative diseases.
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183Leone, V.; Gibbons, S. M.; Martinez, K.; Hutchison, A. L.; Huang, E. Y.; Cham, C. M.; Pierre, J. F.; Heneghan, A. F.; Nadimpalli, A.; Hubert, N. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe 2015, 17, 681– 689, DOI: 10.1016/j.chom.2015.03.006183https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXms1yntrk%253D&md5=56dd299db5987fa956049b7513edb0e6Effects of Diurnal Variation of Gut Microbes and High-Fat Feeding on Host Circadian Clock Function and MetabolismLeone, Vanessa; Gibbons, Sean M.; Martinez, Kristina; Hutchison, Alan L.; Huang, Edmond Y.; Cham, Candace M.; Pierre, Joseph F.; Heneghan, Aaron F.; Nadimpalli, Anuradha; Hubert, Nathaniel; Zale, Elizabeth; Wang, Yunwei; Huang, Yong; Theriault, Betty; Dinner, Aaron R.; Musch, Mark W.; Kudsk, Kenneth A.; Prendergast, Brian J.; Gilbert, Jack A.; Chang, Eugene B.Cell Host & Microbe (2015), 17 (5), 681-689CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)Circadian clocks and metab. are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an addnl. key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain wt. compared to conventionally raised counterparts. Examn. of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary compn. Addnl., specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.
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184Nicholson, J. K.; Holmes, E.; Kinross, J.; Burcelin, R.; Gibson, G.; Jia, W.; Pettersson, S. Host-gut microbiota metabolic interactions. Science 2012, 336, 1262– 1267, DOI: 10.1126/science.1223813184https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XnvFekt7c%253D&md5=a4383140dbfa427c36adb44d30add530Host-Gut Microbiota Metabolic InteractionsNicholson, Jeremy K.; Holmes, Elaine; Kinross, James; Burcelin, Remy; Gibson, Glenn; Jia, Wei; Pettersson, SvenScience (Washington, DC, United States) (2012), 336 (6086), 1262-1267CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review. The compn. and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiol. connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
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185Moran, C. P.; Shanahan, F. Gut microbiota and obesity: role in aetiology and potential therapeutic target. Best Pract. Res. Clin. Gastroenterol. 2014, 28, 585– 597, DOI: 10.1016/j.bpg.2014.07.005185https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1SjsLrN&md5=e1e2e003162e3d957e19b1b2e3dd71e3Gut microbiota and obesity: Role in aetiology and potential therapeutic targetMoran, Carthage P.; Shanahan, FergusBest Practice & Research, Clinical Gastroenterology (2014), 28 (4), 585-597CODEN: BPRCB6 ISSN:. (Elsevier Ltd.)Obesity is epidemic; chronic energy surplus is clearly important in obesity development but other factors are at play. Indigenous gut microbiota are implicated in the aetiopathogenesis of obesity and obesity-related disorders. Evidence from murine models initially suggested a role for the gut microbiota in wt. regulation and the microbiota has been shown to contribute to the low grade inflammation that characterises obesity. The microbiota and its metabolites mediate some of the alterations of the microbiota-gut-brain axis, the endocannabinoid system, and bile acid metab., found in obesity-related disorders. Modulation of the gut microbiota is an attractive proposition for prevention or treatment of obesity, particularly as traditional measures have been sub-optimal.
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186Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012, 490, 55– 60, DOI: 10.1038/nature11450186https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVaqt7fJ&md5=96d88e053af22d9b82d8d96dfab6a147A metagenome-wide association study of gut microbiota in type 2 diabetesQin, Junjie; Li, Yingrui; Cai, Zhiming; Li, Shenghui; Zhu, Jianfeng; Zhang, Fan; Liang, Suisha; Zhang, Wenwei; Guan, Yuanlin; Shen, Dongqian; Peng, Yangqing; Zhang, Dongya; Jie, Zhuye; Wu, Wenxian; Qin, Youwen; Xue, Wenbin; Li, Junhua; Han, Lingchuan; Lu, Donghui; Wu, Peixian; Dai, Yali; Sun, Xiaojuan; Li, Zesong; Tang, Aifa; Zhong, Shilong; Li, Xiaoping; Chen, Weineng; Xu, Ran; Wang, Mingbang; Feng, Qiang; Gong, Meihua; Yu, Jing; Zhang, Yanyan; Zhang, Ming; Hansen, Torben; Sanchez, Gaston; Raes, Jeroen; Falony, Gwen; Okuda, Shujiro; Almeida, Mathieu; LeChatelier, Emmanuelle; Renault, Pierre; Pons, Nicolas; Batto, Jean-Michel; Zhang, Zhaoxi; Chen, Hua; Yang, Ruifu; Zheng, Weimou; Li, Songgang; Yang, Huanming; Wang, Jian; Ehrlich, S. Dusko; Nielsen, Rasmus; Pedersen, Oluf; Kristiansen, Karsten; Wang, JunNature (London, United Kingdom) (2012), 490 (7418), 55-60CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out anal. on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide assocn. study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approx. 60,000 type-2-diabetes-assocd. markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS anal. showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulfate redn. and oxidative stress resistance. An anal. of 23 addnl. individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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187Donohoe, D. R.; Wali, A.; Brylawski, B. P.; Bultman, S. J. Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes. PLoS One 2012, 7, e46589, DOI: 10.1371/journal.pone.0046589187https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFSktrfP&md5=b6ece252ef812a4b2d023eb11283a448Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytesDonohoe, Dallas R.; Wali, Aminah; Brylawski, Bruna P.; Bultman, Scott J.PLoS One (2012), 7 (9), e46589CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)A prodigious no. of microbes inhabit the human body, esp. in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metab., we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germ-free and conventionally-raised C57BL/6 mice. These expts. demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germ-free colonocytes. However, 13C-glucose metabolic-flux expts. and biochem. assays demonstrated that they shifted their glucose metab. away from mitochondrial oxidn./CO2 prodn. and toward increased glycolysis/lactate prodn., which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH) levels and activity. Consistent with perturbed PDH function, the addn. of butyrate, but not glucose, to germ-free colonocytes ex vivo stimulated oxidative metab. As a result of this energetic defect, germ-free colonocytes exhibited a partial block in the G1-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells.
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188Donohoe, D. R.; Garge, N.; Zhang, X.; Sun, W.; O’Connell, T. M.; Bunger, M. K.; Bultman, S. J. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011, 13, 517– 526, DOI: 10.1016/j.cmet.2011.02.018188https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsFalsro%253D&md5=e2df41177d98df47115844f10c2a07fdThe Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian ColonDonohoe, Dallas R.; Garge, Nikhil; Zhang, Xinxin; Sun, Wei; O'Connell, Thomas M.; Bunger, Maureen K.; Bultman, Scott J.Cell Metabolism (2011), 13 (5), 517-526CODEN: CMEEB5; ISSN:1550-4131. (Cell Press)Summary: The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metab. in a general vs. tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germ-free mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metab. including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD+, oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27kip1 phosphorylation, and autophagy. When butyrate is added to germ-free colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor.
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189Tolhurst, G.; Heffron, H.; Lam, Y. S.; Parker, H. E.; Habib, A. M.; Diakogiannaki, E.; Cameron, J.; Grosse, J.; Reimann, F.; Gribble, F. M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012, 61, 364– 371, DOI: 10.2337/db11-1019189https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XltVOlt7Y%253D&md5=fa3f45e6f2dd3b88b217700febe3248fShort-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2Tolhurst, Gwen; Heffron, Helen; Lam, Yu Shan; Parker, Helen E.; Habib, Abdella M.; Diakogiannaki, Eleftheria; Cameron, Jennifer; Grosse, Johannes; Reimann, Frank; Gribble, Fiona M.Diabetes (2012), 61 (2), 364-371CODEN: DIAEAZ; ISSN:0012-1797. (American Diabetes Association, Inc.)Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermn. of "indigestible" prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quant. PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1-secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.
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190de Vos, W. M.; Tilg, H.; Van Hul, M.; Cani, P. D. Gut microbiome and health: mechanistic insights. Gut 2022, 71, 1020– 1032, DOI: 10.1136/gutjnl-2021-326789190https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsFSrs73L&md5=e2b02488e750468564ab871ae5955b8fGut microbiome and health: mechanistic insightsde Vos, Willem M.; Tilg, Herbert; Van Hul, Matthias; Cani, Patrice D.Gut (2022), 71 (5), 1020-1032CODEN: GUTTAK; ISSN:0017-5749. (BMJ)A review. The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of mol. tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metab. are affected. In this review, specific attention is given to provide a crit. evaluation of the current understanding in this field. Numerous mol. mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, shortchain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified mol. actors (ie, endocannabinoids, bioactive lipids, phenolicderived compds., advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5). Altogether, understanding the complexity and the mol. aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.
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191Yeoh, Y. K.; Zuo, T.; Lui, G. C.-Y.; Zhang, F.; Liu, Q.; Li, A. Y.; Chung, A. C.; Cheung, C. P.; Tso, E. Y.; Fung, K. S. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021, 70, 698– 706, DOI: 10.1136/gutjnl-2020-323020191https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtFegtLjK&md5=f488d7a24c822e82b9c627d96687ab09Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19Yeoh, Yun Kit; Zuo, Tao; Lui, Grace Chung-Yan; Zhang, Fen; Liu, Qin; Li, Amy Yl; Chung, Arthur Ck; Cheung, Chun Pan; Tso, Eugene Yk; Fung, Kitty Sc; Chan, Veronica; Ling, Lowell; Joynt, Gavin; Hui, David Shu-Cheong; Chow, Kai Ming; Ng, Susanna So Shan; Li, Timothy Chun-Man; Ng, Rita Wy; Yip, Terry Cf; Wong, Grace Lai-Hung; Chan, Francis Kl; Wong, Chun Kwok; Chan, Paul Ks; Ng, Siew C.Gut (2021), 70 (4), 698-706CODEN: GUTTAK; ISSN:0017-5749. (BMJ)Objective: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome compn., if any, resolve with clearance of the SARS-CoV-2 virus. Methods: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with lab.-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compns. were characterised by shotgun sequencing total DNA extd. from stools. Concns. of inflammatory cytokines and blood markers were measured from plasma. Results: Gut microbiome compn. was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irresp. of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resoln. Moreover, this perturbed compn. exhibited stratification with disease severity concordant with elevated concns. of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. Conclusion: Assocns. between gut microbiota compn., levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resoln. could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
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192Burchill, E.; Lymberopoulos, E.; Menozzi, E.; Budhdeo, S.; McIlroy, J. R.; Macnaughtan, J.; Sharma, N. The Unique Impact of COVID-19 on Human Gut Microbiome Research. Frontiers in Medicine 2021, 8, 652464, DOI: 10.3389/fmed.2021.652464192https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sflt1Sgtg%253D%253D&md5=2f2093b61f3af7cda6158315aa0b2a39The Unique Impact of COVID-19 on Human Gut Microbiome ResearchBurchill Ella; Lymberopoulos Eva; Menozzi Elisa; Budhdeo Sanjay; Sharma Nikhil; Lymberopoulos Eva; Budhdeo Sanjay; Sharma Nikhil; McIlroy James R; Macnaughtan JaneFrontiers in medicine (2021), 8 (), 652464 ISSN:2296-858X.The coronavirus (COVID-19) pandemic has disrupted clinical trials globally, with unique implications for research into the human gut microbiome. In this mini-review, we explore the direct and indirect influences of the pandemic on the gut microbiome and how these can affect research and clinical trials. We explore the direct bidirectional relationships between the COVID-19 virus and the gut and lung microbiomes. We then consider the significant indirect effects of the pandemic, such as repeated lockdowns, increased hand hygiene, and changes to mood and diet, that could all lead to longstanding changes to the gut microbiome at an individual and a population level. Together, these changes may affect long term microbiome research, both in observational as well as in population studies, requiring urgent attention. Finally, we explore the unique implications for clinical trials using faecal microbiota transplants (FMT), which are increasingly investigated as potential treatments for a range of diseases. The pandemic introduces new barriers to participation in trials, while the direct and indirect effects laid out above can present a confounding factor. This affects recruitment and sample size, as well as study design and statistical analyses. Therefore, the potential impact of the pandemic on gut microbiome research is significant and needs to be specifically addressed by the research community and funders.
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193Bernard-Raichon, L.; Venzon, M.; Klein, J.; Axelrad, J. E.; Zhang, C.; Sullivan, A. P.; Hussey, G. A.; Casanovas-Massana, A.; Noval, M. G.; Valero-Jimenez, A. M. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nat. Commun. 2022, 13, 5926, DOI: 10.1038/s41467-022-33395-6193https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xisl2htLnL&md5=d101841387bc8b27c1a0a3f8a7ae843bGut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremiaBernard-Raichon, Lucie; Venzon, Mericien; Klein, Jon; Axelrad, Jordan E.; Zhang, Chenzhen; Sullivan, Alexis P.; Hussey, Grant A.; Casanovas-Massana, Arnau; Noval, Maria G.; Valero-Jimenez, Ana M.; Gago, Juan; Putzel, Gregory; Pironti, Alejandro; Wilder, Evan; Yale IMPACT Research Team; Thorpe, Lorna E.; Littman, Dan R.; Dittmann, Meike; Stapleford, Kenneth A.; Shopsin, Bo; Torres, Victor J.; Ko, Albert I.; Iwasaki, Akiko; Cadwell, Ken; Schluter, JonasNature Communications (2022), 13 (1), 5926CODEN: NCAOBW; ISSN:2041-1723. (Nature Portfolio)Although microbial populations in the gut microbiome are assocd. with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is assocd. with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clin. sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Anal. of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.
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194Chumpitazi, B. P. The gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disorders. Curr. Opin. Gastroenterol. 2020, 36, 147– 154, DOI: 10.1097/MOG.0000000000000608194https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MbhsVyqsA%253D%253D&md5=46619e9dfa4b6fe5b22d6fb770354f1aThe gut microbiome as a predictor of low fermentable oligosaccharides disaccharides monosaccharides and polyols diet efficacy in functional bowel disordersChumpitazi Bruno P; Chumpitazi Bruno PCurrent opinion in gastroenterology (2020), 36 (2), 147-154 ISSN:.PURPOSE OF REVIEW: Fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) dietary restriction ameliorates irritable bowel syndrome (IBS) symptoms; however, not all individuals with IBS respond. Given the gut microbiome's role in carbohydrate fermentation, investigators have evaluated whether the gut microbiome may predict low FODMAP diet efficacy. RECENT FINDINGS: Gut microbiome fermentation, even to the same carbohydrate, is not uniform across all individuals with several factors (e.g. composition) playing a role. In both children and adults with IBS, studies are emerging suggesting the gut microbiome may predict low FODMAP diet efficacy. However, there is significant heterogeneity in the approaches (study population, microbiome assessment methods, statistical techniques, etc.) used amongst these studies. SUMMARY: The gut microbiome holds promise as a predictor of low FODMAP diet efficacy. However, further investigation using standardized approaches to evaluate the microbiome while concomitantly assessing other potential predictors are needed to more rigorously evaluate this area.
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195Leshem, A.; Segal, E.; Elinav, E. The Gut Microbiome and Individual-Specific Responses to Diet. mSystems 2020, 5, e00665– 00620, DOI: 10.1128/mSystems.00665-20195https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXis1ensb%252FL&md5=7233b2ed6a68e52d8a48f7748b4bd049The gut microbiome and individual-specific responses to dietLeshem, Avner; Segal, Eran; Elinav, EranmSystems (2020), 5 (5), e00665CODEN: MSYSBR; ISSN:2379-5077. (American Society for Microbiology)Nutritional content and timing are increasingly appreciated to constitute important human variables collectively impacting all aspects of human physiol. and disease. However, person-specific mechanisms driving nutritional impacts on the human host remain incompletely understood, while current dietary recommendations remain empirical and nonpersonalized. Precision nutrition aims to harness individualized bodies of data, including the human gut microbiome, in predicting person-specific physiol. responses (such as glycemic responses) to food. With these advances notwithstanding, many unknowns remain, including the long-term efficacy of such interventions in delaying or reversing human metabolic disease, mechanisms driving these dietary effects, and the extent of the contribution of the gut microbiome to these processes. We summarize these conceptual advances, while highlighting challenges and means of addressing them in the next decade of study of precision medicine, toward generation of insights that may help to evolve precision nutrition as an effective future tool in a variety of "multifactorial" human disorders.
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196Lepage, P.; Häsler, R.; Spehlmann, M. E.; Rehman, A.; Zvirbliene, A.; Begun, A.; Ott, S.; Kupcinskas, L.; Doré, J.; Raedler, A. Twin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitis. Gastroenterology 2011, 141, 227– 236, DOI: 10.1053/j.gastro.2011.04.011196https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MnltV2lsw%253D%253D&md5=4967b06bdc3199066a51d166b172a9dbTwin study indicates loss of interaction between microbiota and mucosa of patients with ulcerative colitisLepage Patricia; Hasler Robert; Spehlmann Martina E; Rehman Ateequr; Zvirbliene Aida; Begun Alexander; Ott Stephan; Kupcinskas Limas; Dore Joel; Raedler Andreas; Schreiber StefanGastroenterology (2011), 141 (1), 227-36 ISSN:.BACKGROUND & AIMS: Interactions between genetic and environmental factors are believed to be involved in onset and initiation of inflammatory bowel disease. We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium. METHODS: Biopsy were collected from sigmoid colon of UC patients and their healthy twins (discordant twin pairs) and from twins without UC. Microbiota profiles were determined from analysis of 16S ribosomal DNA libraries; messenger RNA profiles were determined by microarray analysis. RESULTS: Patients with UC had dysbiotic microbiota, characterized by less bacterial diversity and more Actinobacteria and Proteobacteria than that of their healthy siblings; healthy siblings from discordant twins had more bacteria from the Lachnospiraceae and Ruminococcaceae families than twins who were both healthy. In twins who were both healthy, 34 mucosal transcripts correlated with bacterial genera, whereas only 25 and 11 correlated with bacteria genera in healthy individuals and their twins with UC, respectively. Transcripts related to oxidative and immune responses were differentially expressed between patients with UC and their healthy twins. CONCLUSIONS: The transcriptional profile of the mucosa appears to interact with the colonic microbiota; this interaction appears to be lost in colon of patients with UC. Bacterial functions, such as butyrate production, might affect mucosal gene expression. Patients with UC had different gene expression profiles and lower levels of biodiversity than their healthy twins, as well as unusual aerobic bacteria. Patients with UC had lower percentages of potentially protective bacterial species than their healthy twins.
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197Manichanh, C.; Borruel, N.; Casellas, F.; Guarner, F. The gut microbiota in IBD. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 599– 608, DOI: 10.1038/nrgastro.2012.152197https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVKmurvN&md5=356ec8125e30b70feafb5b7570c843deThe gut microbiota in IBDManichanh, Chaysavanh; Borruel, Natalia; Casellas, Francesc; Guarner, FranciscoNature Reviews Gastroenterology & Hepatology (2012), 9 (10), 599-608CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. IBD-ulcerative colitis and Crohn's disease-is emerging as a worldwide epidemic. An assocn. between the increased incidence of IBD and environmental factors linked to socioeconomic development has been persistently detected in different parts of the world. The lifestyle in developed countries might impair the natural patterns of microbial colonization of the human gut. The interaction of microbes with mucosal immune compartments in the gut seems to have a major role in priming and regulating immunity. In IBD, mucosal lesions are generated by an excessive or dysregulated immune response against commensal microbes in the gut. In individuals with a genetic susceptibility to IBD, abnormal microbial colonization of the gastrointestinal tract might be the origin of such dysregulation. Developments in gene-sequencing technologies, as well as increased availability of powerful bioinformatic tools, have enabled novel insights into the microbial compn. of the human gut microbiota and the effect of microbial communities on human physiol. and disease. Studies that used these technologies indicate that dysbiosis (i.e., abnormal microbiota compn.) and decreased complexity of the gut microbial ecosystem are common features in patients with Crohn's disease or ulcerative colitis. Whether such changes are a cause or a consequence of the disease remains to be elucidated.
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198Tong, M.; Li, X.; Wegener Parfrey, L.; Roth, B.; Ippoliti, A.; Wei, B.; Borneman, J.; McGovern, D. P.; Frank, D. N.; Li, E. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One 2013, 8, e80702, DOI: 10.1371/journal.pone.0080702198https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjtlyltw%253D%253D&md5=d5dd9ca97aca3f3fcfd9e39b22785b5cA modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel diseaseTong, Maomeng; Li, Xiaoxiao; Parfrey, Laura Wegener; Roth, Bennett; Ippoliti, Andrew; Wei, Bo; Borneman, James; McGovern, Dermot P. B.; Frank, Daniel N.; Li, Ellen; Horvath, Steve; Knight, Rob; Braun, JonathanPLoS One (2013), 8 (11), e80702/1-e80702/14CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial compn. are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecol. analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quant. reproducible features of microbial compn. in normal and IBD mucosa. We sequenced 16S rRNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clin. remission). CD and UC patients showed a redn. in phylogenetic diversity and shifts in microbial compn., comparable to previous studies using conventional mucosal biopsies. Anal. of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals and their compn. and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were assocd. with healthy, CD or UC disease states. Imputed metagenome anal. indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metab. pathways relevant to host-pathogen interaction in the disease-assocd. modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecol. relevant to IBD.
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199Guinane, C. M.; Cotter, P. D. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap. Adv. Gastroenterol. 2013, 6, 295– 308, DOI: 10.1177/1756283X13482996199https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sjmsFGltQ%253D%253D&md5=af7a6aea1965ce4b76dd186765f08f9fRole of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organGuinane Caitriona M; Cotter Paul DTherapeutic advances in gastroenterology (2013), 6 (4), 295-308 ISSN:1756-283X.The human gut microbiota has become the subject of extensive research in recent years and our knowledge of the resident species and their potential functional capacity is rapidly growing. Our gut harbours a complex community of over 100 trillion microbial cells which influence human physiology, metabolism, nutrition and immune function while disruption to the gut microbiota has been linked with gastrointestinal conditions such as inflammatory bowel disease and obesity. Here, we review the many significant recent studies that have centred on further enhancing our understanding of the complexity of intestinal communities as well as their genetic and metabolic potential. These have provided important information with respect to what constitutes a 'healthy gut microbiota' while furthering our understanding of the role of gut microbes in intestinal diseases. We also highlight recently developed genomic and other tools that are used to study the gut microbiome and, finally, we consider the manipulation of the gut microbiota as a potential therapeutic option to treat chronic gastrointestinal disease.
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200Kassam, Z.; Lee, C. H.; Yuan, Y.; Hunt, R. H. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am. J. Gastroenterol. 2013, 108, 500– 508, DOI: 10.1038/ajg.2013.59200https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3svnvVKmtQ%253D%253D&md5=9bcde5d19419ee5dc5752e597c14b057Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysisKassam Zain; Lee Christine H; Yuan Yuhong; Hunt Richard HThe American journal of gastroenterology (2013), 108 (4), 500-8 ISSN:.OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI. METHODS: An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups. RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2)=33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI -0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years. CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
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201Tang, W. H.; Kitai, T.; Hazen, S. L. Gut Microbiota in Cardiovascular Health and Disease. Circ. Res. 2017, 120, 1183– 1196, DOI: 10.1161/CIRCRESAHA.117.309715201https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXlt1ens7g%253D&md5=5ff9db227ee9ce736705587ad43ae882Gut Microbiota in Cardiovascular Health and DiseaseTang, W. H. Wilson; Kitai, Takeshi; Hazen, Stanley L.Circulation Research (2017), 120 (7), 1183-1196CODEN: CIRUAL; ISSN:0009-7330. (Lippincott Williams & Wilkins)Significant interest in recent years has focused on gut microbiota-host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the compn. of gut microbiota assocd. with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addn. to alterations in gut microbiota compn., the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiol. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N-oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addn. to these metab.-dependent pathways, metab.-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure-assocd. splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiol. and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.
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202Jiang, H. Y.; Zhang, X.; Yu, Z. H.; Zhang, Z.; Deng, M.; Zhao, J. H.; Ruan, B. Altered gut microbiota profile in patients with generalized anxiety disorder. J. Psychiatr. Res. 2018, 104, 130– 136, DOI: 10.1016/j.jpsychires.2018.07.007202https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c7gt1Kqsw%253D%253D&md5=cd4cd04e4c92d8d72dbd3f497c468f40Altered gut microbiota profile in patients with generalized anxiety disorderJiang Hai-Yin; Zhang Xue; Deng Min; Yu Zheng-He; Zhang Zhe; Zhao Jian-Hua; Ruan BingJournal of psychiatric research (2018), 104 (), 130-136 ISSN:.Close relationships have recently been established between gut microbiota and some mental disorders. Here, we performed a systematic comparative analysis of the gut microbiome in patients with generalized anxiety disorder (GAD) and healthy controls (HCs). We first conducted a cross-sectional study of 40 patients with GAD in the active state and 36 HCs. Second, subgroup analysis consisting of 12 antidepressant-naive patients and 22 controls was performed to validate the results. Finally, a prospective study was performed in a subgroup of nine patients with GAD who underwent analysis in the active state of anxiety and in remission. Compared with the HCs, we found markedly decreased microbial richness and diversity, distinct metagenomic composition with reduced short-chain fatty acid (SCFA)-producing bacteria (associated with a healthy status) and overgrowth of bacteria, such as Escherichia-Shigella, Fusobacterium and Ruminococcus gnavus. Unexpectedly, these changes in the genera were not reversed in remissive GAD. This study identified microbiota dysbiosis of gut microbiota in GAD patients, suggesting that targeting the microbiome may be a useful therapeutic and preventive target for GAD.
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203Chen, Y. H.; Bai, J.; Wu, D.; Yu, S. F.; Qiang, X. L.; Bai, H.; Wang, H. N.; Peng, Z. W. Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. J. Affect. Disord. 2019, 259, 56– 66, DOI: 10.1016/j.jad.2019.08.014203https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1art7%252FO&md5=f4453fa8729d92eaee7c4c0514840797Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment responseChen, Yi-huan; Bai, Jie; Wu, Di; Yu, Shou-fen; Qiang, Xiao-ling; Bai, Hua; Wang, Hua-ning; Peng, Zheng-wuJournal of Affective Disorders (2019), 259 (), 56-66CODEN: JADID7; ISSN:0165-0327. (Elsevier Inc.)Assocns. between abnormal gut microbiome compns. and anxiety-like behaviors are well established. However, it is unknown whether the gut microbiome compn. is assocd. with the severity of generalized anxiety disorder (GAD) and relief from clin. symptoms in patients. Stool samples from 36 patients with active GAD (A-GAD group) and 24 matched healthy control subjects (HC group) were analyzed by 16S rRNA gene sequencing. Anxiety was assessed with the Hamilton Anxiety Rating Scale and the Self-rating Anxiety Scale, and global assessments of functioning were performed at baseline and 1 mo after drug treatment. Gut microbiome compns. were altered in A-GAD patients, with fewer operational taxonomic units and lower fecal bacterial α-diversity. Specifically, Firmicutes and Tenericutes abundances were lower in A-GAD patients, and several genera were differentially represented in the A-GAD and HC groups. The abundances of Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, and Prevotella_9 correlated neg. with the anxiety severity and pos. with anxiety redn., whereas the abundances of Bacteroides and Escherichia-Shigella were pos. assocd. with anxiety severity. The sample sizes were small and the stool samples were collected only at baseline therefore, a causal assocn. between changes in intestinal flora and disease remission was not established. Altered gut microbiome compn. may contribute to GAD pathogenesis and remission.
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204Hemmings, S. M. J.; Malan-Müller, S.; van den Heuvel, L. L.; Demmitt, B. A.; Stanislawski, M. A.; Smith, D. G.; Bohr, A. D.; Stamper, C. E.; Hyde, E. R.; Morton, J. T. The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study. Psychosom. Med. 2017, 79, 936– 946, DOI: 10.1097/PSY.0000000000000512204https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjmvVCmsw%253D%253D&md5=13291869f8793210e263a4abfa875e97The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory StudyHemmings Sian M J; Malan-Muller Stefanie; van den Heuvel Leigh L; Demmitt Brittany A; Stanislawski Maggie A; Smith David G; Bohr Adam D; Stamper Christopher E; Hyde Embriette R; Morton James T; Marotz Clarisse A; Siebler Philip H; Braspenning Maarten; Van Criekinge Wim; Hoisington Andrew J; Brenner Lisa A; Postolache Teodor T; McQueen Matthew B; Krauter Kenneth S; Knight Rob; Seedat Soraya; Lowry Christopher APsychosomatic medicine (2017), 79 (8), 936-946 ISSN:.OBJECTIVE: Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls to identify potential differences in microbial diversity or microbial community structure. METHODS: The Clinician-Administered PTSD Scale for DSM-5 was used to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA gene V3/V4 amplicons were generated and sequenced. Microbial community structure, α-diversity, and β-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD. RESULTS: There were no differences between PTSD and TE control groups in α- or β-diversity measures (e.g., α-diversity: Shannon index, t = 0.386, p = .70; β-diversity, on the basis of analysis of similarities: Bray-Curtis test statistic = -0.033, p = .70); however, random forest analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher Clinician-Administered PTSD Scale scores (r = -0.387, p = .035). CONCLUSIONS: In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.
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205Stevens, B. R.; Goel, R.; Seungbum, K.; Richards, E. M.; Holbert, R. C.; Pepine, C. J.; Raizada, M. K. Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut 2018, 67, 1555– 1557, DOI: 10.1136/gutjnl-2017-314759205https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvVKlsLk%253D&md5=99b454cb63378624dd008fcce23b1593Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depressionStevens, Bruce R.; Goel, Ruby; Seungbum, Kim; Richards, Elaine M.; Holbert, Richard C.; Pepine, Carl J.; Raizada, Mohan K.Gut (2018), 67 (8), 1555-1557CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)This article relates to increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression .
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206Kelly, J. R.; Borre, Y.; O'Brien, C.; Patterson, E.; El Aidy, S.; Deane, J.; Kennedy, P. J.; Beers, S.; Scott, K.; Moloney, G. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J. Psychiatr. Res. 2016, 82, 109– 118, DOI: 10.1016/j.jpsychires.2016.07.019206https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3nsFalsw%253D%253D&md5=508851100916cd45c333e8f2eb862c2dTransferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the ratKelly John R; Clarke Gerard; Borre Yuliya; Kennedy Paul J; Beers Sasja; Scott Karen; Moloney Gerard; Hoban Alan E; Fitzgerald Patrick; O' Brien Ciaran; Patterson Elaine; El Aidy Sahar; Deane Jennifer; Ross Paul; Stanton Catherine; Scott Lucinda; Cryan John F; Dinan Timothy GJournal of psychiatric research (2016), 82 (), 109-18 ISSN:.The gut microbiota interacts with the host via neuroimmune, neuroendocrine and neural pathways. These pathways are components of the brain-gut-microbiota axis and preclinical evidence suggests that the microbiota can recruit this bidirectional communication system to modulate brain development, function and behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine dysregulation. However, the extent to which changes in gut microbiota composition and function mediate the dysregulation of these pathways is unknown. Thirty four patients with major depression and 33 matched healthy controls were recruited. Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein were determined by ELISA. Plasma tryptophan and kynurenine were determined by HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota transplantation was prepared from a sub group of depressed patients and controls and transferred by oral gavage to a microbiota-deficient rat model. We demonstrate that depression is associated with decreased gut microbiota richness and diversity. Fecal microbiota transplantation from depressed patients to microbiota-depleted rats can induce behavioural and physiological features characteristic of depression in the recipient animals, including anhedonia and anxiety-like behaviours, as well as alterations in tryptophan metabolism. This suggests that the gut microbiota may play a causal role in the development of features of depression and may provide a tractable target in the treatment and prevention of this disorder.
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207Lin, P.; Ding, B.; Feng, C.; Yin, S.; Zhang, T.; Qi, X.; Lv, H.; Guo, X.; Dong, K.; Zhu, Y. Prevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorder. J. Affect. Disord. 2017, 207, 300– 304, DOI: 10.1016/j.jad.2016.09.051207https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2srgtl2isw%253D%253D&md5=abf902c0dc205474615200100340069ePrevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorderLin Ping; Ding Bingyu; Feng Chunyan; Yin Shuwei; Zhang Ting; Qi Xin; Lv Huiying; Guo Xiaokui; Dong Ke; Zhu Yongzhang; Li QingtianJournal of affective disorders (2017), 207 (), 300-304 ISSN:.BACKGROUND: The diagnosis of major depression disorder (MDD) and other mental disorders were depended on some subjective survey scales. There are confirmed relationship between the gut flora and the mental states of MDD patients. METHODS: The V3-V4 region of the 16S rRNA gene was extracted from the fecal microbial communities in MDD patients, PCR amplified and sequenced on the Illumina Miseq platform. RESULTS: More phylum Firmicutes, less Bacteroidetes, and more genus Prevotella, Klebsiella, Streptococcus and Clostridium XI were found in MDD patients. The changes of the proportion of Prevotella and Klebsiella were consistent with Hamilton depression rating scale. LIMITATIONS: The conclusion was limited by small sample sizes and potential uncontrollable influence factors on fecal microbiota. DISCUSSION: Prevotella and Klebsiella proportion in fecal microbial communities should be concerned in the diagnosis and therapeutic monitoring of MDD in future.
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208Gough, E.; Shaikh, H.; Manges, A. R. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin. Infect. Dis. 2011, 53, 994– 1002, DOI: 10.1093/cid/cir632208https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3Mbhs1emsA%253D%253D&md5=323ed1a1e99f6c06f7c045c917ed5945Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infectionGough Ethan; Shaikh Henna; Manges Amee RClinical infectious diseases : an official publication of the Infectious Diseases Society of America (2011), 53 (10), 994-1002 ISSN:.Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.
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209Craciun, C. I.; Neag, M. A.; Catinean, A.; Mitre, A. O.; Rusu, A.; Bala, C.; Roman, G.; Buzoianu, A. D.; Muntean, D. M.; Craciun, A. E. The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus. Biomedicines 2022, 10, 308, DOI: 10.3390/biomedicines10020308209https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XlsFars7g%253D&md5=c673653b5e07d22dc660deb87be09dbeThe Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes MellitusCraciun, Cristian-Ioan; Neag, Maria-Adriana; Catinean, Adrian; Mitre, Andrei-Otto; Rusu, Adriana; Bala, Cornelia; Roman, Gabriela; Buzoianu, Anca-Dana; Muntean, Dana-Maria; Craciun, Anca-ElenaBiomedicines (2022), 10 (2), 308CODEN: BIOMID; ISSN:2227-9059. (MDPI AG)A review. Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its assocns. with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the compn. of gut microbiota, but it is unclear how this, in turn, may influence metab. The main objective of this review is to evaluate the pathogenetic assocn. between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.
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210van Nood, E.; Vrieze, A.; Nieuwdorp, M.; Fuentes, S.; Zoetendal, E. G.; de Vos, W. M.; Visser, C. E.; Kuijper, E. J.; Bartelsman, J. F. W. M.; Tijssen, J. G. P. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. New England Journal of Medicine 2013, 368, 407– 415, DOI: 10.1056/NEJMoa1205037210https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXitVelsbs%253D&md5=9e739f9ad764896267b832e89666c9fbDuodenal infusion of donor feces for recurrent clostridium difficilevan Nood, Els; Vrieze, Anne; Nieuwdorp, Max; Fuentes, Susana; Zoetendal, Erwin G.; de Vos, Willem M.; Visser, Caroline E.; Kuijper, Ed J.; Bartelsman, Joep F. W. M.; Tijssen, Jan G. P.; Speelman, Peter; Dijkgraaf, Marcel G. W.; Keller, Josbert J.New England Journal of Medicine (2013), 368 (5), 407-415CODEN: NEJMAG; ISSN:0028-4793. (Massachusetts Medical Society)BACKGROUND Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection. METHODS We randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a soln. of donor feces through a nasoduodenal tube; a std. vancomycin regimen (500 mg orally four times per day for 14 days); or a std. vancomycin regimen with bowel lavage. The primary end point was the resoln. of diarrhea assocd. with C. difficile infection without relapse after 10 wk. RESULTS The study was stopped after an interim anal. Of 16 patients in the infusion group, 13 (81%) had resoln. of C. difficile-assocd. diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resoln. in 2 patients. Resoln. of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were obsd. except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species. CONCLUSIONS The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin.
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211Hamilton, M. J.; Weingarden, A. R.; Sadowsky, M. J.; Khoruts, A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am. J. Gastroenterol. 2012, 107, 761– 767, DOI: 10.1038/ajg.2011.482211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38vhsFOgug%253D%253D&md5=374660d41abfb3c8f52bfb76d82e0606Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infectionHamilton Matthew J; Weingarden Alexa R; Sadowsky Michael J; Khoruts AlexanderThe American journal of gastroenterology (2012), 107 (5), 761-7 ISSN:.OBJECTIVES: While fecal microbiota transplantation (FMT) is historically known to be an effective means to treat recurrent Clostridium difficile infection (CDI) refractory to standard antibiotic therapies, the procedure is rarely performed. At least some of the reasons for limited availability are those of practicality, including aesthetic concerns and costs of donor screening. The objective of this study was to overcome these barriers in our clinical FMT program. METHODS: We report clinical experience with 43 consecutive patients who were treated with FMT for recurrent CDI since inception of this program at the University of Minnesota. During this time, we simplified donor identification and screening by moving from patient-identified individual donors to standard volunteer donors. Material preparation shifted from the endoscopy suite to a standardized process in the laboratory, and ultimately to banking frozen processed fecal material that is ready to use when needed. RESULTS: Standardization of material preparation significantly simplified the practical aspects of FMT without loss of apparent efficacy in clearing recurrent CDI. Approximately 30% of the patients had underlying inflammatory bowel disease, and FMT was equally effective in this group. CONCLUSIONS: Several key steps in the standardization of donor material preparation significantly simplified the clinical practice of FMT for recurrent CDI in patients failing antibiotic therapy.
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212Zafar, H.; Saier, M. H., Jr. Gut Bacteroides species in health and disease. Gut Microbes 2021, 13, 1848158, DOI: 10.1080/19490976.2020.1848158There is no corresponding record for this reference.
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213Chen, Y.; Yang, Y.; Gu, J. Clinical Implications of the Associations Between Intestinal Microbiome and Colorectal Cancer Progression. Cancer Manag. Res. 2020, 12, 4117– 4128, DOI: 10.2147/CMAR.S240108213https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFals7bO&md5=8b18fbdd0f6f9a6d9700a6a4468eededClinical implications of the associations between intestinal microbiome and colorectal cancer progressionChen, Yongkang; Yang, Yong; Gu, JinCancer Management and Research (2020), 12 (), 4117-4128CODEN: CMRACP; ISSN:1179-1322. (Dove Medical Press Ltd.)Intestinal microbiome influences host immunity and several diseases, including cancer, in their areas of colonization. Microbial dysbiosis and over-colonization of specific microbes within the colorectal mucosa can impact the progress of carcinogenesis. Investigations initially focused on the mechanisms by which the intestinal microbiome initiates or promotes the development of colorectal cancer, including DNA damage, induction of chromosomal instability, and regulation of host immune responses. Some studies on the clinicopathol. features have reported that specific strains present at high abundance are assocd. with advanced stage and pos. lymph nodes in colorectal cancer. In this context, we reviewed the relationship between the intestinal microbiome and the clin. features (patient age, disease staging, prognosis, etc.) of patients with colorectal cancer, and evaluated the potential pathogenesis caused by the intestinal microbiome in disease progress. This article assessed whether changes in distinct species or strains occur during the period of cancer advancement. Overall, age grouping does not bring about significant differences in the constitution of microbiome. The disease stages show their distinct distribution in some species and strains. Oncogenic species are generally enriched in patients with poor prognosis, including low infiltration of CD3+ T cells, poor differentiation, widespread invasion, high microsatellite instability, CpG island methylator phenotype, BRAF mutation, short overall survival, and disease-free survival. The implications of those changes we discussed may assist in comprehensive understanding of the tumorigenesis of colorectal cancer from a microbiol. perspective, finding potential biomarkers for colorectal cancer.
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214Bullman, S.; Pedamallu, C. S.; Sicinska, E.; Clancy, T. E.; Zhang, X.; Cai, D.; Neuberg, D.; Huang, K.; Guevara, F.; Nelson, T. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017, 358, 1443– 1448, DOI: 10.1126/science.aal5240214https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFGmtrzI&md5=05bc221abb6825e8934c4b24ce4e7b99Analysis of Fusobacterium persistence and antibiotic response in colorectal cancerBullman, Susan; Pedamallu, Chandra S.; Sicinska, Ewa; Clancy, Thomas E.; Zhang, Xiaoyang; Cai, Diana; Neuberg, Donna; Huang, Katherine; Guevara, Fatima; Nelson, Timothy; Chipashvili, Otari; Hagan, Timothy; Walker, Mark; Ramachandran, Aruna; Diosdado, Begona; Serna, Garazi; Mulet, Nuria; Landolfi, Stefania; Ramon y Cajal, Santiago; Fasani, Roberta; Aguirre, Andrew J.; Ng, Kimmie; Elez, Elena; Ogino, Shuji; Tabernero, Josep; Fuchs, Charles S.; Hahn, William C.; Nuciforo, Paolo; Meyerson, MatthewScience (Washington, DC, United States) (2017), 358 (6369), 1443-1448CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Colorectal cancers comprise a complex mixt. of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its assocd. microbiome - including Bacteroides, Selenomonas, and Prevotella species - is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization anal. revealed that Fusobacterium is predominantly assocd. with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its assocd. microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-assocd. colorectal cancer.
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215Cammann, D.; Lu, Y.; Cummings, M. J.; Zhang, M. L.; Cue, J. M.; Do, J.; Ebersole, J.; Chen, X.; Oh, E. C.; Cummings, J. L. Genetic correlations between Alzheimer’s disease and gut microbiome genera. Sci. Rep. 2023, 13, 5258, DOI: 10.1038/s41598-023-31730-5215https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXmvFOisb4%253D&md5=7129ddcd4fb02a9070cb68b6b50d6411Genetic correlations between Alzheimer's disease and gut microbiome generaCammann, Davis; Lu, Yimei; Cummings, Melika J.; Zhang, Mark L.; Cue, Joan Manuel; Do, Jenifer; Ebersole, Jeffrey; Chen, Xiangning; Oh, Edwin C.; Cummings, Jeffrey L.; Chen, JingchunScientific Reports (2023), 13 (1), 5258CODEN: SRCEC3; ISSN:2045-2322. (Nature Portfolio)Abstr.: A growing body of evidence suggests that dysbiosis of the human gut microbiota is assocd. with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide assocn. study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the "best-fit" model implemented in PRSice-2 and detd. the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS anal. in a replication sample (GenADA case/control: 799/778) and then performed a meta-anal. with the PRS results from both samples. Finally, we conducted a linear regression anal. to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically assocd. with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-anal. with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly assocd. with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD assocn. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was pos. correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly assocd. with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.
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216Silva, Y. P.; Bernardi, A.; Frozza, R. L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020, 11, 25, DOI: 10.3389/fendo.2020.00025216https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB387ksFagug%253D%253D&md5=83e69c9f7ec5454ed8e5abfc5bb3ba2bThe Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain CommunicationSilva Ygor Parladore; Frozza Rudimar Luiz; Bernardi AndressaFrontiers in endocrinology (2020), 11 (), 25 ISSN:1664-2392.A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.
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217Manning, L. P.; Yao, C. K.; Biesiekierski, J. R. Therapy of IBS: Is a Low FODMAP Diet the Answer?. Front. Psychiatry 2020, 11, 865, DOI: 10.3389/fpsyt.2020.00865217https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3s7mvVakug%253D%253D&md5=fdc19d32efa4ed24984b261fe4f145daTherapy of IBS: Is a Low FODMAP Diet the Answer?Manning Lauren P; Biesiekierski Jessica R; Yao C KFrontiers in psychiatry (2020), 11 (), 865 ISSN:1664-0640.Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder with a worldwide prevalence of 11%. It is characterized by abdominal pain and altered bowel habits in the absence of underlying unique pathology. The condition is associated with poor quality of life and high use of healthcare resources required for management. The low FODMAP diet (LFD) is a recognized treatment for symptom management of IBS; however, approximately 30% of patients do not respond. The aim of this review was to understand the effectiveness and application of the LFD compared with other dietary and non-dietary interventions. Ten studies were included, eight of which assessed the LFD against other dietary interventions including traditional dietary advice, modified National Institute for Health and Care Excellence guidelines, a high FODMAP diet, gluten-free diet and Mediterranean diet, generalized dietary advice, probiotics, and a sham diet. Two studies compared a LFD to non-diet interventions of gut directed hypnotherapy or yoga. The findings clearly support the LFD as an effective treatment in IBS, and although it highlights the role for microbiota and current psychosocial state, it remains challenging to identify what combination of treatments may be best to ensure a personalized approach and overall higher response rates to IBS therapy.
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218Nanayakkara, W. S.; Skidmore, P. M.; O’Brien, L.; Wilkinson, T. J.; Gearry, R. B. Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date. Clin. Exp. Gastroenterol. 2016, 9, 131– 142, DOI: 10.2147/CEG.S86798218https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmsFWmsbY%253D&md5=33bf40a2ba4a041768f0ab024ef8405bEfficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to dateNanayakkara, Wathsala S.; Skidmore, Paula M. L.; O'Brien, Leigh; Wilkinson, Tim J.; Gearry, Richard B.Clinical and Experimental Gastroenterology (2016), 9 (), 131-142CODEN: CEGLAD; ISSN:1178-7023. (Dove Medical Press Ltd.)This review summarizes the published clin. studies concerning the management of irritable bowel syndrome (IBS) using restriction of Fermentable Oligosaccharide, Disaccharide, Monosaccharide, and Polyols in the diet (low FODMAP diet). In recent years, the data supporting low FODMAP diet for the management of IBS symptoms have emerged, including several randomized controlled trials, case-control studies, and other observational studies. Unlike most dietary manipulations tried in the past to alleviate gastrointestinal symptoms of IBS, all studies on low FODMAP diet have consistently shown symptomatic benefits in the majority of patients with IBS. However, dietary adherence by the patients and clear dietary intervention led by specialized dietitians appear to be vital for the success of the diet. Up to 86% of patients with IBS find improvement in overall gastrointestinal symptoms as well as individual symptoms such as abdominal pain, bloating, constipation, diarrhea, abdominal distention, and flatulence following the diet. FODMAP restriction reduces the osmotic load and gas prodn. in the distal small bowel and the proximal colon, providing symptomatic relief in patients with IBS. Long-term health effects of a low FODMAP diet are not known; however, stringent FODMAP restriction is not recommended owing to risks of inadequate nutrient intake and potential adverse effects from altered gut microbiota. In conclusion, the evidence to date strongly supports the efficacy of a low FODMAP diet in the treatment of IBS. Further studies are required to understand any potential adverse effects of long-term restriction of FODMAPs.
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219Tegegne, B. A.; Kebede, B. Probiotics, their prophylactic and therapeutic applications in human health development: A review of the literature. Heliyon 2022, 8, e09725 DOI: 10.1016/j.heliyon.2022.e09725219https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitFOmurrO&md5=4dbad5bba5cdeba7fe84bb34dba094dfProbiotics, their prophylactic and therapeutic applications in human health development: A review of the literatureTegegne, Bantayehu Addis; Kebede, BekaluHeliyon (2022), 8 (6), e09725CODEN: HELICI; ISSN:2405-8440. (Elsevier Ltd.)Antibiotics do not differentiate between good and bad germs, disrupting normal microflora and causing vitamin deficiency in the human body. They also kill healthy bacteria in the gut and genital tract on a large scale, weakening the host's defense mechanism. Probiotics are a colony of bacteria that live in our intestines and are regarded as a metabolic 'organ' due to their beneficial effects on human health, including metab. and immunol. function. They are used in clin. settings to prevent and treat conditions such as diarrhoea, colon cancer, hypertension, diabetes, acute pancreatitis, Helicobacter pylori infection, ventilator-assocd. pneumonia, migraine and autism. Probiotics may modify immunol. activity by increasing innate and adaptive immune responses, altering microbial habitat in the intestine, improving gut barrier function, competitive adherence to the mucosa and epithelium, and producing antimicrobial compds. The aim of this study is to index that further in depth researches to be conducted on probiotics pivotal role in the prophylaxis and therapeutic usage for a variety of disease that may or may not have treatment alternatives. Key words such as probiotics, microbiota, prophylactics, and therapeutic applications were searched extensively in research databases such as PubMed, PubMed Central (PMC), Scopus, Web of Science, Research Gate, Google Scholar, and Cochrane Library. This concise narrative review article summarized primarily the history, selection, mechanism/mode of action, recent advances in prophylactic and therapeutic applications, and future directions in the use of probiotics for prophylactic and therapeutic applications.
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220Aponte, M.; Murru, N.; Shoukat, M. Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current Perspective. Front. Microbiol. 2020, 11, 562048, DOI: 10.3389/fmicb.2020.562048220https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3s7gtVertg%253D%253D&md5=a2b4712a68074da0900a9a33b293bf93Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current PerspectiveAponte Maria; Shoukat Mahtab; Murru NicolettaFrontiers in microbiology (2020), 11 (), 562048 ISSN:1664-302X.Probiotics are considered as the twenty-first century panpharmacon due to their competent remedial power to cure from gastrointestinal dysbiosis, systematic metabolic diseases, and genetic impairments up to complicated neurodegenerative disorders. They paved the way for an innovative managing of various severe diseases through palatable food products. The probiotics' role as a "bio-therapy" increased their significance in food and medicine due to many competitive advantages over traditional treatment therapies. Their prophylactic and therapeutic potential has been assessed through hundreds of preclinical and clinical studies. In addition, the food industry employs probiotics as functional and nutraceutical ingredients to enhance the added value of food product in terms of increased health benefits. However, regardless of promising health-boosting effects, the probiotics' efficacy still needs an in-depth understanding of systematic mechanisms and factors supporting the healthy actions.
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221Noonan, S.; Zaveri, M.; Macaninch, E.; Martyn, K. Food & mood: a review of supplementary prebiotic and probiotic interventions in the treatment of anxiety and depression in adults. BMJ. Nutrition, Prevention & Health 2020, 3, 351, DOI: 10.1136/bmjnph-2019-000053221https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srnsl2ksQ%253D%253D&md5=004737e64c73a75826b75cacfa992c6fFood & mood: a review of supplementary prebiotic and probiotic interventions in the treatment of anxiety and depression in adultsNoonan Sanjay; Zaveri Meena; Macaninch Elaine; Martyn KathyBMJ nutrition, prevention & health (2020), 3 (2), 351-362 ISSN:.BACKGROUND: A bidirectional relationship exists between the brain and the gastrointestinal tract. Foods containing bacteria that positively influence the gastrointestinal microbiome are termed, probiotics; compounds that promote the flourishing of these bacteria are termed, prebiotics. Whether microbiome influencing therapies could treat psychiatric conditions, including depression and anxiety, is an area of interest. Presently, no established consensus for such treatment exists. METHODS: This systematic review analyses databases and grey literature sites to investigate pre and/or probiotics as treatments for depression and/or anxiety disorders. Articles included are from within 15 years. Pre-determined inclusion exclusion criteria were applied, and articles were appraised for their quality using a modified-CASP checklist. This review focuses specifically on quantitative measures from patients with clinical diagnoses of depression and/or anxiety disorders. RESULTS: 7 studies were identified. All demonstrated significant improvements in one or more of the outcomes measuring the of effect taking pre/probiotics compared with no treatment/placebo, or when compared to baseline measurements. DISCUSSION: Our review suggests utilising pre/probiotic may be a potentially useful adjunctive treatment. Furthermore, patients with certain co-morbidities, such as IBS, might experience greater benefits from such treatments, given that pre/probiotic are useful treatments for other conditions that were not the primary focus of this discourse. Our results are limited by several factors: sample sizes (adequate, though not robust); short study durations, long-term effects and propensity for remission undetermined. CONCLUSION: Our results affirm that pre/probiotic therapy warrants further investigation. Efforts should aim to elucidate whether the perceived efficacy of pre/probiotic therapy in depression and/or anxiety disorders can be replicated in larger test populations, and whether such effects are maintained through continued treatment, or post cessation. Interventions should also be investigated in isolation, not combination, to ascertain where the observed effects are attributable to. Efforts to produce mechanistic explanations for such effect should be a priority.
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222MACFARLANE, S.; MACFARLANE, G. T.; CUMMINGS, J. H. Review article: prebiotics in the gastrointestinal tract. Aliment. Pharmacol. Ther. 2006, 24, 701– 714, DOI: 10.1111/j.1365-2036.2006.03042.x222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFGqsrvI&md5=326f16c92c2ddf341b9877e55abf9107Review article: prebiotics in the gastrointestinal tractMacFarlane, S.; MacFarlane, G. T.; Cummings, J. H.Alimentary Pharmacology and Therapeutics (2006), 24 (5), 701-714CODEN: APTHEN; ISSN:0269-2813. (Blackwell Publishing Ltd.)A review. Prebiotics are short-chain carbohydrates that alter the compn., or metab., of the gut microbiota in a beneficial manner. It is therefore expected that prebiotics will improve health in a way similar to probiotics, while at the same time being cheaper, and carrying less risk and being easier to incorporate into the diet than probiotics. To review published evidence for prebiotic effects on gut function and human health. We searched the Science Citation Index with the terms prebiotic, microbiota, gut bacteria, large intestine, mucosa, bowel habit, constipation, diarrhea, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, calcium and cancer, focusing principally on studies in humans and reports in the English language. Search of the Cochrane Library did not identify any clin. study or meta-anal. on this topic. Three prebiotics, oligofructose, galacto-oligosaccharides and lactulose, clearly alter the balance of the large bowel microbiota by increasing bifidobacteria and Lactobacillus nos. These carbohydrates are fermented and give rise to short-chain fatty acid and intestinal gas; however, effects on bowel habit are relatively small. Randomized-controlled trials of their effect in a clin. context are few, although animal studies show anti-inflammatory effects in inflammatory bowel disease, while calcium absorption is increased. It is still early days for prebiotics, but they offer the potential to modify the gut microbial balance in such a way as to bring direct health benefits cheaply and safely.
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223Dinan, K.; Dinan, T. Antibiotics and mental health: The good, the bad and the ugly. J. Int. Med. 2022, 292, 858– 869, DOI: 10.1111/joim.13543223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MfmvFCmsw%253D%253D&md5=3fcf2535686849b95f568aa4bfe2dbcaAntibiotics and mental health: The good, the bad and the uglyDinan Katherine; Dinan TimothyJournal of internal medicine (2022), 292 (6), 858-869 ISSN:.Antibiotics are recognised as, on occasion, producing psychiatric side effects, most notably depression and anxiety. Apart from antimicrobial activity, antibiotics have multiple off-target effects. The brain-gut-microbiota axis has multiple sites for off-target activity, which may produce either positive or negative antibiotic effects. Here we review how antibiotics impact mental health by acting through the brain-gut-microbiota axis. Microbes in the gut influence brain function by acting through the vagus nerve or by altering the production of short-chain fatty acids or the amino acid tryptophan, the building block of serotonin. Not all antimicrobial actions of antibiotics have a negative impact. The first antidepressant discovered was actually an antibiotic: isoniazid is an antibacterial drug developed for treating tuberculosis. Minocycline, which enters the brain and mediates its effects through microglia, shows antidepressant activity. Some antibiotics bring about a significant decrease in gut microbial diversity, and this is viewed as a risk factor for depression. Other risk factors induced by antibiotics include altered gut barrier function, activation of the hypothalamic-pituitary-adrenal axis, reducing levels of brain-derived neurotrophic factor or oxytocin and alteration of vagal tone. Although most patients taking antibiotics do not suffer from an iatrogenic psychiatric disorder, some do. As clinicians, we need to keep this in mind. The development of new antibiotics is primarily focused on antibiotic resistance, but efforts should be made to reduce off-target brain-gut-microbiota effects resulting in mental health problems.
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224Karakan, T.; Ozkul, C.; Küpeli Akkol, E.; Bilici, S.; Sobarzo-Sánchez, E.; Capasso, R. Gut-Brain-Microbiota Axis: Antibiotics and Functional Gastrointestinal Disorders. Nutrients 2021, 13, 389, DOI: 10.3390/nu13020389224https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXnt1Ggtrc%253D&md5=b62057fce5fb8e10658783a224a8ce59Gut-brain-microbiota axis: antibiotics and functional gastrointestinal disordersKarakan, Tarkan; Ozkul, Ceren; Akkol, Esra Kuepeli; Bilici, Saniye; Sobarzo-Sanchez, Eduardo; Capasso, RaffaeleNutrients (2021), 13 (2), 389CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Gut microbiota compn. and function are major areas of research for functional gastrointestinal disorders. There is a connection between gastrointestinal tract and central nervous system and this is mediated by neurotransmitters, inflammatory cytokines, the vagus nerve and the hypothalamic-pituitary-adrenal axis. Functional gastrointestinal disorders are prevalent diseases affecting more than one third of the population. The etiol. of these disorders is not clarified. Visceral hyperalgesia is the main hypothesis for explaining clin. symptoms, however gut-brain axis disorder is a new terminol. for functional disorders. In this review, microbiota-gut-brain axis connection pathways and related disorders are discussed. Antibiotics are widely used in developed countries and recent evidence indicates antibiotic-induced dysbiosis as an important factor for functional disorders. Antibiotics exert neg. effects on gut microbiota compn. and functions. Antibiotic-induced dysbiosis is a major factor for occurrence of post-infectious irritable bowel syndrome. Cognitive and mood disorders are also frequent in functional gastrointestinal disorders. Animal and human trials show strong evidence for the causal relationship between gut microbiota and brain functions. Therapeutic implications of these newly defined pathogenic pathways are also discussed.
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225Xu, H. M.; Huang, H. L.; Zhou, Y. L.; Zhao, H. L.; Xu, J.; Shou, D. W.; Liu, Y. D.; Zhou, Y. J.; Nie, Y. Q. Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain. Gastroenterol. Res. Pract. 2021, 2021, 6699268, DOI: 10.1155/2021/6699268225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srmslahsQ%253D%253D&md5=6be72c579a7c6003fb60bbe182a0e30eFecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the BrainXu Hao-Ming; Huang Hong-Li; Zhou You-Lian; Zhao Hai-Lan; Xu Jing; Shou Di-Wen; Liu Yan-Di; Zhou Yong-Jian; Nie Yu-QiangGastroenterology research and practice (2021), 2021 (), 6699268 ISSN:1687-6121.Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).
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226Doll, J. P. K.; Vázquez-Castellanos, J. F.; Schaub, A.-C.; Schweinfurth, N.; Kettelhack, C.; Schneider, E.; Yamanbaeva, G.; Mählmann, L.; Brand, S.; Beglinger, C. Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression─Case Report. Front. Psychiatry 2022, 13, 815422, DOI: 10.3389/fpsyt.2022.815422226https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2Mzgt1aitQ%253D%253D&md5=bb6fd052bb3cfe6ba95ac48f9377e2f9Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case ReportDoll Jessica P K; Schaub Anna-Chiara; Schweinfurth Nina; Kettelhack Cedric; Schneider Else; Yamanbaeva Gulnara; Mahlmann Laura; Borgwardt Stefan; Schmidt Andre; Lang Undine E; Vazquez-Castellanos Jorge F; Raes Jeroen; Brand Serge; Brand Serge; Brand Serge; Brand Serge; Brand Serge; Beglinger Christoph; Borgwardt StefanFrontiers in psychiatry (2022), 13 (), 815422 ISSN:1664-0640.Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment.
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227Waller, K. M. J.; Leong, R. W.; Paramsothy, S. An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases. J. Gastroenterol. Hepatol. 2022, 37, 246– 255, DOI: 10.1111/jgh.15731227https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2cjoslyisQ%253D%253D&md5=f99ac67810d7f66adee95e075d5ce2a4An update on fecal microbiota transplantation for the treatment of gastrointestinal diseasesWaller Karen M J; Leong Rupert W; Paramsothy Sudarshan; Waller Karen M J; Leong Rupert W; Paramsothy Sudarshan; Leong Rupert W; Paramsothy SudarshanJournal of gastroenterology and hepatology (2022), 37 (2), 246-255 ISSN:.Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.
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228Hetterich, L.; Stengel, A. Psychotherapeutic Interventions in Irritable Bowel Syndrome. Front. Psychiatry 2020, 11, 286, DOI: 10.3389/fpsyt.2020.00286228https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38voslWisg%253D%253D&md5=eda0cab2d8bca2378779a256d71f2cd1Psychotherapeutic Interventions in Irritable Bowel SyndromeHetterich Larissa; Stengel Andreas; Stengel AndreasFrontiers in psychiatry (2020), 11 (), 286 ISSN:1664-0640.Irritable bowel syndrome (IBS) is a frequent functional gastrointestinal disorder. The patients complain about various symptoms like change in bowel habits, constipation or diarrhea, abdominal pain, and meteorism leading to a great reduction in quality of life. The pathophysiology is complex and best explained using the biopsychosocial model encompassing biological, psychological as well as (psycho)social factors. In line with the multitude of underlying factors, the treatment is comprised of a multitude of components. Often, patients start with lifestyle changes and dietary advice followed by medical treatment. However, also psychotherapy is an important treatment option for patients with IBS and should not be restricted to those with psychiatric comorbidities. Several evidence-based psychotherapeutic treatment options exist such as psychoeducation, self-help, cognitive behavioral therapy, psychodynamic psychotherapy, hypnotherapy, mindfulness-based therapy, and relaxation therapy which will be discussed in the present review.
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229Wildes, J. E.; Bedell, A.; Graham, A. K.; Kells, M. Brain-gut psychotherapies: Promising tools to address gastrointestinal problems in patients with eating disorders. Int. J. Eat. Disord. 2021, 54, 1063– 1067, DOI: 10.1002/eat.23555229https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c%252FmvVCqsQ%253D%253D&md5=c1bc34b65c12c712ec05ad55fcac0d4eBrain-gut psychotherapies: Promising tools to address gastrointestinal problems in patients with eating disordersWildes Jennifer E; Bedell Alyse; Kells Meredith; Graham Andrea K; Graham Andrea KThe International journal of eating disorders (2021), 54 (6), 1063-1067 ISSN:.Gastrointestinal (GI) problems are common in individuals with eating disorders (EDs) and associated with distress, impairment, and increased healthcare utilization. GI symptoms may be exacerbated by meals and other interventions central to ED recovery thereby contributing to negative clinical outcomes. Informed by models emphasizing the role of the brain-gut axis in the expression of GI symptoms, this article describes a program of research to adapt "brain-gut psychotherapies" for EDs. First, the role of the brain-gut axis in GI symptoms is described, and evidence-based brain-gut psychotherapies are reviewed, with an emphasis on cognitive behavioral therapy for GI disorders and gut-directed hypnotherapy. Next, future directions for research in EDs to (a) understand the impact of GI symptoms on illness course and outcome; (b) clarify target engagement; (c) evaluate brain-gut psychotherapies; and (d) optimize intervention reach and delivery are described. We present a conceptual model that emphasizes GI-specific anxiety and altered gut physiology as targets of brain-gut psychotherapies in EDs, and discuss several issues that need to be addressed in designing clinical trials to test these interventions. We also describe how engagement with multidisciplinary stakeholders and use of digital tools could speed translation from the laboratory to clinical settings.
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230Laird, K. T.; Tanner-Smith, E. E.; Russell, A. C.; Hollon, S. D.; Walker, L. S. Comparative efficacy of psychological therapies for improving mental health and daily functioning in irritable bowel syndrome: A systematic review and meta-analysis. Clin. Psychol. Rev. 2017, 51, 142– 152, DOI: 10.1016/j.cpr.2016.11.001230https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2snoslykuw%253D%253D&md5=de6427a342c2a2a66e5d5a248aa4db29Comparative efficacy of psychological therapies for improving mental health and daily functioning in irritable bowel syndrome: A systematic review and meta-analysisLaird Kelsey T; Tanner-Smith Emily E; Russell Alexandra C; Walker Lynn S; Hollon Steven DClinical psychology review (2017), 51 (), 142-152 ISSN:.Previous meta-analyses have shown that psychotherapy improves gastrointestinal symptoms in adults with irritable bowel syndrome (IBS); however, the impact on functioning in daily activities is unknown. Meta-analysis was used to estimate the effect of psychotherapy on mental health and daily functioning in adults with IBS. An extensive literature search located 28 eligible randomized controlled trials (RCTs) providing outcome data for mental health and 18 RCTs providing data for daily functioning. Compared to a mixed group of control conditions, psychotherapy produced significantly greater improvements to mental health (d-=0.41) and daily functioning (d-=0.43). Cognitive behavior therapy (CBT) was evaluated in the largest number of trials (21 trials), followed by hypnosis (4 trials), psychodynamic (3 trials), and relaxation (2 trials). The psychotherapeutic modalities were comparable with respect to their effect on mental health. CBT produced the greatest improvements to daily functioning, and this effect was significantly larger than that produced by relaxation therapy. These results have important clinical implications for treatment of adults with IBS.
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231Colomier, E.; Algera, J.; Melchior, C. Pharmacological Therapies and Their Clinical Targets in Irritable Bowel Syndrome With Diarrhea. Front. Pharmacol. 2021, 11, 629026, DOI: 10.3389/fphar.2020.629026There is no corresponding record for this reference.
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232World Health Organization. Pharmacological treatment of mental disorders in primary health care. WHO Press: Geneva, Switzerland, 2009.There is no corresponding record for this reference.
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233Fikree, A.; Byrne, P. Management of functional gastrointestinal disorders. Clin Med. (Lond) 2021, 21, 44– 52, DOI: 10.7861/clinmed.2020-0980233https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3srjsFKhtQ%253D%253D&md5=6507a255122bb692c704d190651a1e1fManagement of functional gastrointestinal disordersFikree Asma; Byrne PeterClinical medicine (London, England) (2021), 21 (1), 44-52 ISSN:.Functional gastrointestinal (GI) disorders (eg irritable bowel syndrome and functional dyspepsia) are very common conditions which are associated with very poor quality of life and high healthcare utilisation. They are caused by disorders of GI functioning, namely altered gut sensitivity, motility, microbiota, immune functioning and central nervous system processing. They cause chronic symptoms throughout the gut (eg pain, dyspepsia and altered bowel habit), all of which are made worse by maladaptive patient behaviours, stress and psychological comorbidity. Management involves a biopsychosocial approach involving changes in lifestyle and diet, addressing coexisting psychological comorbidity and using medication to treat underlying pathophysiology. Pharmacological treatment with antispasmodics, neuromodulators, motility agents and antidepressants is effective. Psychotherapy in motivated individuals is equally effective. Success of treatment is increased by a good doctor-patient relationship and so this needs to be taken into account during the consultation.
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234Tierney, B. T.; Yang, Z.; Luber, J. M.; Beaudin, M.; Wibowo, M. C.; Baek, C.; Mehlenbacher, E.; Patel, C. J.; Kostic, A. D. The Landscape of Genetic Content in the Gut and Oral Human Microbiome. Cell Host Microbe 2019, 26, 283– 295.e288, DOI: 10.1016/j.chom.2019.07.008234https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1Sit7zL&md5=add2f2ab5cb4b28803e5e50f0192a132The Landscape of Genetic Content in the Gut and Oral Human MicrobiomeTierney, Braden T.; Yang, Zhen; Luber, Jacob M.; Beaudin, Marc; Wibowo, Marsha C.; Baek, Christina; Mehlenbacher, Eleanor; Patel, Chirag J.; Kostic, Aleksandar D.Cell Host & Microbe (2019), 26 (2), 283-295.e8CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)Meta-anal. of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were "singletons," or unique to a single metagenomic sample. Singletons were enriched for different functions (compared with non-singletons) and arose from sub-population-specific microbial strains. Overall, these results provide potential bases for the unexplained heterogeneity obsd. in microbiome-derived human phenotypes.
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235International Human Genome Sequencing Consortium Finishing the euchromatic sequence of the human genome. Nature 2004, 431, 931– 945, DOI: 10.1038/nature03001There is no corresponding record for this reference.
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236Liu, J.; Tan, Y.; Cheng, H.; Zhang, D.; Feng, W.; Peng, C. Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives. Aging Dis. 2022, 13, 1106– 1126, DOI: 10.14336/AD.2022.0104236https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MbgsFGktg%253D%253D&md5=e5d73d8cf72eb8a31636780eb1a15a27Functions of Gut Microbiota Metabolites, Current Status and Future PerspectivesLiu Juan; Tan Yuzhu; Cheng Hao; Zhang Dandan; Feng Wuwen; Peng Cheng; Cheng Hao; Zhang Dandan; Feng Wuwen; Peng ChengAging and disease (2022), 13 (4), 1106-1126 ISSN:2152-5250.Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health.
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237Heijtz, R. D.; Wang, S.; Anuar, F.; Qian, Y.; Björkholm, B.; Samuelsson, A.; Hibberd, M. L.; Forssberg, H.; Pettersson, S. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 3047– 3052, DOI: 10.1073/pnas.1010529108237https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXisVans7k%253D&md5=120bcfa2cddbab592375dd2e671cf069Normal gut microbiota modulates brain development and behaviorHeijtz, Rochellys Diaz; Wang, Shugui; Anuar, Farhana; Qian, Yu; Bjorkholm, Britta; Samuelsson, Annika; Hibberd, Martin L.; Forssberg, Hans; Pettersson, SvenProceedings of the National Academy of Sciences of the United States of America (2011), 108 (7), 3047-3052, S3047/1-S3047/5CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Microbial colonization of mammals is an evolution-driven process that modulate host physiol., many of which are assocd. with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is assocd. with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
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238Sudo, N.; Chida, Y.; Aiba, Y.; Sonoda, J.; Oyama, N.; Yu, X.-N.; Kubo, C.; Koga, Y. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. Journal of Physiology 2004, 558, 263– 275, DOI: 10.1113/jphysiol.2004.063388238https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXmtFWhtro%253D&md5=eed1b25785166e5444218089f6abe1fePostnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in miceSudo, Nobuyuki; Chida, Yoichi; Aiba, Yuji; Sonoda, Junko; Oyama, Naomi; Yu, Xiao-Nian; Kubo, Chiharu; Koga, YasuhiroJournal of Physiology (Oxford, United Kingdom) (2004), 558 (1), 263-275CODEN: JPHYA7; ISSN:0022-3751. (Blackwell Publishing Ltd.)Indigenous microbiota have several beneficial effects on host physiol. functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiol. system response. To test the idea that such microbes may affect the development of neural systems that govern the endocrine response to stress, we investigated hypothalamic-pituitary-adrenal (HPA) reaction to stress by comparing germ-free (GF), specific pathogen free (SPF) and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not in response to stimulation with ether. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassocn. with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced the response to stress. Importantly, the enhanced HPA response of GF mice was partly cor. by reconstitution with SPF feces at an early stage, but not by any reconstitution exerted at a later stage, which therefore indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of the HPA stress response in mice.
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239Needham, B. D.; Funabashi, M.; Adame, M. D.; Wang, Z.; Boktor, J. C.; Haney, J.; Wu, W.-L.; Rabut, C.; Ladinsky, M. S.; Hwang, S.-J. A gut-derived metabolite alters brain activity and anxiety behaviour in mice. Nature 2022, 602, 647– 653, DOI: 10.1038/s41586-022-04396-8239https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xjs12kurk%253D&md5=3bf0205ec8a2eeef83f05239deedbfddA gut-derived metabolite alters brain activity and anxiety behaviour in miceNeedham, Brittany D.; Funabashi, Masanori; Adame, Mark D.; Wang, Zhuo; Boktor, Joseph C.; Haney, Jillian; Wu, Wei-Li; Rabut, Claire; Ladinsky, Mark S.; Hwang, Son-Jong; Guo, Yumei; Zhu, Qiyun; Griffiths, Jessica A.; Knight, Rob; Bjorkman, Pamela J.; Shapiro, Mikhail G.; Geschwind, Daniel H.; Holschneider, Daniel P.; Fischbach, Michael A.; Mazmanian, Sarkis K.Nature (London, United Kingdom) (2022), 602 (7898), 647-653CODEN: NATUAS; ISSN:1476-4687. (Nature Portfolio)Integration of sensory and mol. inputs from the environment shapes animal behavior. A major site of exposure to environmental mols. is the gastrointestinal tract, in which dietary components are chem. transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behavior3, modulates neurotransmitter prodn. in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was assocd. with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been assocd. with behavioral outcomes7,9-14. Accordingly, we obsd. that mice exposed to 4EPS displayed anxiety-like behaviors, and pharmacol. treatments that promote oligodendrocyte differentiation prevented the behavioral effects of 4EPS. These findings reveal that a gut-derived mol. influences complex behaviors in mice through effects on oligodendrocyte function and myelin patterning in the brain.
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240Gacias, M.; Gaspari, S.; Santos, P.-M. G.; Tamburini, S.; Andrade, M.; Zhang, F.; Shen, N.; Tolstikov, V.; Kiebish, M. A.; Dupree, J. L. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. eLife 2016, 5, e13442, DOI: 10.7554/eLife.13442240https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXmtlGmsL8%253D&md5=ba6cf36afd24925d0ac0af6a370c1632Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behaviourGacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae; Tamburini, Sabrina; Andrade, Monica; Zhang, Fan; Shen, Nan; Tolstikov, Vladimir; Kiebish, Michael A.; Dupree, Jeffrey L.; Zachariou, Venetia; Clemente, Jose C.; Casaccia, PatriziaeLife (2016), 5 (), e13442/1-e13442/27CODEN: ELIFA8; ISSN:2050-084X. (eLife Sciences Publications Ltd.)Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not obsd. in C57BL/6 mice. This was not obsd. in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic anal. identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.
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241Vuong, H. E.; Pronovost, G. N.; Williams, D. W.; Coley, E. J. L.; Siegler, E. L.; Qiu, A.; Kazantsev, M.; Wilson, C. J.; Rendon, T.; Hsiao, E. Y. The maternal microbiome modulates fetal neurodevelopment in mice. Nature 2020, 586, 281– 286, DOI: 10.1038/s41586-020-2745-3241https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFWmurvO&md5=41f2ee099d320a2359f5d5e194bda294The maternal microbiome modulates fetal neurodevelopment in miceVuong, Helen E.; Pronovost, Geoffrey N.; Williams, Drake W.; Coley, Elena J. L.; Siegler, Emily L.; Qiu, Austin; Kazantsev, Maria; Wilson, Chantel J.; Rendon, Tomiko; Hsiao, Elaine Y.Nature (London, United Kingdom) (2020), 586 (7828), 281-286CODEN: NATUAS; ISSN:0028-0836. (Nature Research)'Dysbiosis' of the maternal gut microbiome, in response to challenges such as infection1, altered diet2 and stress3 during pregnancy, has been increasingly assocd. with abnormalities in brain function and behavior of the offspring4. However, it is unclear whether the maternal gut microbiome influences neurodevelopment during crit. prenatal periods and in the absence of environmental challenges. Here we investigate how depletion and selective reconstitution of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibited reduced brain expression of genes related to axonogenesis, deficient thalamocortical axons and impaired outgrowth of thalamic axons in response to cell-extrinsic factors. Gnotobiotic colonization of microbiome-depleted dams with a limited consortium of bacteria prevented abnormalities in fetal brain gene expression and thalamocortical axonogenesis. Metabolomic profiling revealed that the maternal microbiome regulates numerous small mols. in the maternal serum and the brains of fetal offspring. Select microbiota-dependent metabolites promoted axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with these metabolites abrogated deficiencies in fetal thalamocortical axons. Manipulation of the maternal microbiome and microbial metabolites during pregnancy yielded adult offspring with altered tactile sensitivity in two aversive somatosensory behavioral tasks, but no overt differences in many other sensorimotor behaviors. Together, our findings show that the maternal gut microbiome promotes fetal thalamocortical axonogenesis, probably through signalling by microbially modulated metabolites to neurons in the developing brain.
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242Wei, G. Z.; Martin, K. A.; Xing, P. Y.; Agrawal, R.; Whiley, L.; Wood, T. K.; Hejndorf, S.; Ng, Y. Z.; Low, J. Z. Y.; Rossant, J. Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor. Proc. Natl. Acad. Sci. U. S. A. 2021, 118, e2021091118, DOI: 10.1073/pnas.2021091118242https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsFSns7bM&md5=6a699c1abd8c4de300b6ec4a4d8ebff9Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptorWei, George Zhang; Martin, Katherine A.; Xing, Peter Yuli; Agrawal, Ruchi; Whiley, Luke; Wood, Thomas K.; Hejndorf, Sophia; Ng, Yong Zhi; Yan Low, Jeremy Zhi; Rossant, Janet; Nechanitzky, Robert; Holmes, Elaine; Nicholson, Jeremy K.; Tan, Eng-King; Matthews, Paul M.; Pettersson, SvenProceedings of the National Academy of Sciences of the United States of America (2021), 118 (27), e2021091118CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)While modulatory effects of gut microbes on neurol. phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic d. protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not obsd. with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a mol. pathway connecting gut microbiota compn. and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.
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243Kang, D.-W.; Adams, J. B.; Gregory, A. C.; Borody, T.; Chittick, L.; Fasano, A.; Khoruts, A.; Geis, E.; Maldonado, J.; McDonough-Means, S. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 2017, 5, 10, DOI: 10.1186/s40168-016-0225-7243https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1c7pt1Gksw%253D%253D&md5=9c81c841550249c4ef4b2c5ccc9e52caMicrobiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label studyKang Dae-Wook; Maldonado Juan; Krajmalnik-Brown Rosa; Adams James B; Geis Elizabeth; Pollard Elena L; Gregory Ann C; Sullivan Matthew B; Gregory Ann C; Chittick Lauren; Roux Simon; Sullivan Matthew B; Borody Thomas; Chittick Lauren; Roux Simon; Sullivan Matthew B; Fasano Alessio; Khoruts Alexander; Khoruts Alexander; Sadowsky Michael J; Khoruts Alexander; McDonough-Means Sharon; Sadowsky Michael J; Lipson Karen Schwarzberg; Caporaso J Gregory; Sullivan Matthew B; Caporaso J Gregory; Krajmalnik-Brown RosaMicrobiome (2017), 5 (1), 10 ISSN:.BACKGROUND: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10(13) bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. RESULTS: MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). CONCLUSIONS: This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. TRIAL REGISTRATION: This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
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244Korpela, K.; Helve, O.; Kolho, K. L.; Saisto, T.; Skogberg, K.; Dikareva, E.; Stefanovic, V.; Salonen, A.; Andersson, S.; de Vos, W. M. Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study. Cell 2020, 183, 324– 334.e325, DOI: 10.1016/j.cell.2020.08.047244https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFyqt7%252FP&md5=8cf28050f83c4ecf2c922f3f744ee098Maternal Fecal Microbiota Transplantation in Cesarean-born infants rapidly restores normal Gut Microbial Development: A Proof-of-Concept StudyKorpela, Katri; Helve, Otto; Kolho, Kaija-Leena; Saisto, Terhi; Skogberg, Kirsi; Dikareva, Evgenia; Stefanovic, Vedran; Salonen, Anne; Andersson, Sture; de Vos, Willem M.Cell (Cambridge, MA, United States) (2020), 183 (2), 324-334.e5CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a dild. fecal sample from their own mothers, taken 3 wk prior to delivery. All seven infants had an uneventful clin. course during the 3-mo follow-up and showed no adverse effects. The temporal development of the fecal microbiota compn. of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clin. and microbiol. screening.
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245Wikoff, W. R.; Anfora, A. T.; Liu, J.; Schultz, P. G.; Lesley, S. A.; Peters, E. C.; Siuzdak, G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 3698– 3703, DOI: 10.1073/pnas.0812874106245https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjt1Gksrk%253D&md5=2056708fdbccc79f1fa28b5ecfdc694eMetabolomics analysis reveals large effects of gut microflora on mammalian blood metabolitesWikoff, William R.; Anfora, Andrew T.; Liu, Jun; Schultz, Peter G.; Lesley, Scott A.; Peters, Eric C.; Siuzdak, GaryProceedings of the National Academy of Sciences of the United States of America (2009), 106 (10), 3698-3703CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Although it has long been recognized that the enteric community of bacteria that inhabit the human distal intestinal track broadly impacts human health, the biochem. details that underlie these effects remain largely undefined. Here, we report a broad MS-based metabolomics study that demonstrates a surprisingly large effect of the gut "microbiome" on mammalian blood metabolites. Plasma exts. from germ-free mice were compared with samples from conventional (conv) animals by using various MS-based methods. Hundreds of features were detected in only 1 sample set, with the majority of these being unique to the conv animals, whereas ≈10% of all features obsd. in both sample sets showed significant changes in their relative signal intensity. Amino acid metabolites were particularly affected. For example, the bacterial-mediated prodn. of bioactive indole-contg. metabolites derived from tryptophan such as indoxyl sulfate and the antioxidant indole-3-propionic acid (IPA) was impacted. Prodn. of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacterium Clostridium sporogenes. Multiple org. acids contg. Ph groups were also greatly increased in the presence of gut microbes. A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was obsd., suggesting that the gut microflora has a direct impact on the drug metab. capacity of the host. Together, these results suggest a significant interplay between bacterial and mammalian metab.
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246Dodd, D.; Spitzer, M. H.; Van Treuren, W.; Merrill, B. D.; Hryckowian, A. J.; Higginbottom, S. K.; Le, A.; Cowan, T. M.; Nolan, G. P.; Fischbach, M. A. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 2017, 551, 648– 652, DOI: 10.1038/nature24661246https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvVynsLnJ&md5=df143bcb59e17bb7cc33dffbd843689eA gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolitesDodd, Dylan; Spitzer, Matthew H.; Van Treuren, William; Merrill, Bryan D.; Hryckowian, Andrew J.; Higginbottom, Steven K.; Le, Anthony; Cowan, Tina M.; Nolan, Garry P.; Fischbach, Michael A.; Sonnenburg, Justin L.Nature (London, United Kingdom) (2017), 551 (7682), 648-652CODEN: NATUAS; ISSN:0028-0836. (Nature Research)The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small mols. commonly reach concns. similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates arom. amino acid metabolites. Our results reveal that this pathway produces twelve compds., nine of which are known to accumulate in host serum. All three arom. amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the mol. output of the gut bacterial community.
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247Barrett, E.; Ross, R. P.; O’Toole, P. W.; Fitzgerald, G. F.; Stanton, C. γ-Aminobutyric acid production by culturable bacteria from the human intestine. J. Appl. Microbiol. 2012, 113, 411– 417, DOI: 10.1111/j.1365-2672.2012.05344.x247https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFCktbvF&md5=dcf88e5c216766fbe060d473078d696eγ-Aminobutyric acid production by culturable bacteria from the human intestineBarrett, E.; Ross, R. P.; O'Toole, P. W.; Fitzgerald, G. F.; Stanton, C.Journal of Applied Microbiology (2012), 113 (2), 411-417CODEN: JAMIFK; ISSN:1364-5072. (Wiley-Blackwell)The aim was to assess the ability of human intestinally derived strains of Lactobacillus and Bifidobacterium to produce γ-aminobutyric acid (GABA). Strains of Lactobacillus and Bifidobacterium were grown in medium contg. monosodium glutamate (MSG). Growth of the bacteria and conversion of MSG to GABA were measured. Of 91 intestinally derived bacteria assessed, one Lactobacillus strain and four strains of Bifidobacterium produced GABA. Lactobacillus brevisDPC6108 was the most efficient of the strains tested, converting up to 100% of MSG to GABA. The ability of the cultured intestinal strains to produce GABA was investigated using a simple pH-controlled anaerobic faeces-based fermn., supplemented with 30 mg ml-1 MSG. The addn. of Lact. brevisDPC6108 to a faeces-based fermn. significantly increased the GABA concn. (P < 0·001), supporting the notion that this biosynthesis could occur in vivo. The prodn. of GABA by bifidobacteria exhibited considerable interspecies variation. Lactobacillus brevis and Bifidobacterium dentium were the most efficient GABA producers among the range of strains tested. The addn. of Lact. brevisDPC6108 to the culturable gut microbiota increased the GABA concn. in fermented faecal slurry at physiol. pH. Identification of optimal MSG conversion to GABA by particular cultured elements of the commensal intestinal microbiota and the demonstration that this can occur under simulated in vivo conditions offer new prospects for microbiota modulation to promote health.
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248Asano, Y.; Hiramoto, T.; Nishino, R.; Aiba, Y.; Kimura, T.; Yoshihara, K.; Koga, Y.; Sudo, N. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303, G1288– 1295, DOI: 10.1152/ajpgi.00341.2012There is no corresponding record for this reference.
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249Pocivavsek, A.; Wu, H.-Q.; Potter, M. C.; Elmer, G. I.; Pellicciari, R.; Schwarcz, R. Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and Memory. Neuropsychopharmacology 2011, 36, 2357– 2367, DOI: 10.1038/npp.2011.127249https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtFyms7bN&md5=68f97aa462679aadd3af5b5eb106e084Fluctuations in Endogenous Kynurenic Acid Control Hippocampal Glutamate and MemoryPocivavsek, Ana; Wu, Hui-Qiu; Potter, Michelle C.; Elmer, Greg I.; Pellicciari, Roberto; Schwarcz, RobertNeuropsychopharmacology (2011), 36 (11), 2357-2367CODEN: NEROEW; ISSN:0893-133X. (Nature Publishing Group)Kynurenic acid (KYNA), an astrocyte-derived metabolite, antagonizes the α7 nicotinic acetylcholine receptor (α7nAChR) and, possibly, the glycine co-agonist site of the NMDA receptor at endogenous brain concns. As both receptors are involved in cognitive processes, KYNA elevations may aggravate, whereas redns. may improve, cognitive functions. We tested this hypothesis in rats by examg. the effects of acute up- or downregulation of endogenous KYNA on extracellular glutamate in the hippocampus and on performance in the Morris water maze (MWM). Applied directly by reverse dialysis, KYNA (30-300 nM) reduced, whereas the specific kynurenine aminotransferase-II inhibitor (S)-4-(ethylsulfonyl)benzoylalanine (ESBA; 0.3-3 mM) raised, extracellular glutamate levels in the hippocampus. Co-application of KYNA (100 nM) with ESBA (1 mM) prevented the ESBA-induced glutamate increase. Comparable effects on hippocampal glutamate levels were seen after intra-cerebroventricular (i.c.v.) application of the KYNA precursor kynurenine (1 mM, 10 μl) or ESBA (10 mM, 10 μl), resp. In sep. animals, i.c.v. treatment with kynurenine impaired, whereas i.c.v. ESBA improved, performance in the MWM. I.c.v. co-application of KYNA (10 μM) eliminated the pro-cognitive effects of ESBA. Collectively, these studies show that KYNA serves as an endogenous modulator of extracellular glutamate in the hippocampus and regulates hippocampus-related cognitive function. Our results suggest that pharmacol. interventions leading to acute redns. in hippocampal KYNA constitute an effective strategy for cognitive improvement. This approach might be esp. useful in the treatment of cognitive deficits in neurol. and psychiatric diseases that are assocd. with increased brain KYNA levels. Neuropsychopharmacol. (2011) 36, 2357-2367; doi:10.1038/npp.2011.127; published online 27 July 2011.
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250Potter, M. C.; Elmer, G. I.; Bergeron, R.; Albuquerque, E. X.; Guidetti, P.; Wu, H.-Q.; Schwarcz, R. Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive Behavior. Neuropsychopharmacology 2010, 35, 1734– 1742, DOI: 10.1038/npp.2010.39250https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnsVOnsbY%253D&md5=3f26ceee98561f8a40d694645f16f2f9Reduction of Endogenous Kynurenic Acid Formation Enhances Extracellular Glutamate, Hippocampal Plasticity, and Cognitive BehaviorPotter, Michelle C.; Elmer, Greg I.; Bergeron, Richard; Albuquerque, Edson X.; Guidetti, Paolo; Wu, Hui-Qiu; Schwarcz, RobertNeuropsychopharmacology (2010), 35 (8), 1734-1742CODEN: NEROEW; ISSN:0893-133X. (Nature Publishing Group)At endogenous brain concns., the astrocyte-derived metabolite kynurenic acid (KYNA) antagonizes the α7 nicotinic acetylcholine receptor and, possibly, the glycine co-agonist site of the NMDA receptor. The functions of these two receptors, which are intimately involved in synaptic plasticity and cognitive processes, may, therefore, be enhanced by redns. in brain KYNA levels. This concept was tested in mice with a targeted deletion of kynurenine aminotransferase II (KAT II), a major biosynthetic enzyme of brain KYNA. At 21 days of age, KAT II knock-out mice had reduced hippocampal KYNA levels (-71%) and showed significantly increased performance in three cognitive paradigms that rely in part on the integrity of hippocampal function, namely object exploration and recognition, passive avoidance, and spatial discrimination. Moreover, compared with wild-type controls, hippocampal slices from KAT II-deficient mice showed a significant increase in the amplitude of long-term potentiation in vitro. These functional changes were accompanied by reduced extracellular KYNA (-66%) and increased extracellular glutamate (+51%) concns., measured by hippocampal microdialysis in vivo. Taken together, a picture emerges in which a redn. in the astrocytic formation of KYNA increases glutamatergic tone in the hippocampus and enhances cognitive abilities and synaptic plasticity. Our studies raise the prospect that interventions aimed specifically at reducing KYNA formation in the brain may constitute a promising mol. strategy for cognitive improvement in health and disease.
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251Reigstad, C. S.; Salmonson, C. E.; Rainey, J. F., III; Szurszewski, J. H.; Linden, D. R.; Sonnenburg, J. L.; Farrugia, G.; Kashyap, P. C. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2015, 29, 1395– 1403, DOI: 10.1096/fj.14-259598251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmsFahsr4%253D&md5=e94fb047d3a97dc2f4ee14acf6ef9877Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cellsReigstad, Christopher S.; Salmonson, Charles E.; Rainey, John F., III; Szurszewski, Joseph H.; Linden, David R.; Sonnenburg, Justin L.; Farrugia, Gianrico; Kashyap, Purna C.FASEB Journal (2015), 29 (4), 1395-1403CODEN: FAJOEC; ISSN:0892-6638. (Federation of American Societies for Experimental Biology)Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To det. the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P < 0.01] and chromogranin A (neuroendocrine secretion; P < 0.01), with no effect on monoamine oxidase A (serotonin catabolism), serotonin receptor 5-HT4, or mouse serotonin transporter. HM and CR mice also had increased colonic Tph1 protein (P < 0.05) and 5-HT concns. (GF, 17 ± 3 ng/mg; HM, 25 ± 2 ng/mg; and CR, 35 ± 3 ng/mg; P < 0.05). Enterochromaffin (EC) cell nos. (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT prodn. and homeostasis.
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252Yano, J. M.; Yu, K.; Donaldson, G. P.; Shastri, G. G.; Ann, P.; Ma, L.; Nagler, C. R.; Ismagilov, R. F.; Mazmanian, S. K.; Hsiao, E. Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 2015, 161, 264– 276, DOI: 10.1016/j.cell.2015.02.047252https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXmsVWqsLk%253D&md5=5c9ef92794dedb7b9fe60b5d4b825a46Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin BiosynthesisYano, Jessica M.; Yu, Kristie; Donaldson, Gregory P.; Shastri, Gauri G.; Ann, Phoebe; Ma, Liang; Nagler, Cathryn R.; Ismagilov, Rustem F.; Mazmanian, Sarkis K.; Hsiao, Elaine Y.Cell (Cambridge, MA, United States) (2015), 161 (2), 264-276CODEN: CELLB5; ISSN:0092-8674. (Cell Press)The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metab. of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a crit. role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiol., modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concns. of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biol. processes.
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253Bellono, N. W.; Bayrer, J. R.; Leitch, D. B.; Castro, J.; Zhang, C.; O’Donnell, T. A.; Brierley, S. M.; Ingraham, H. A.; Julius, D. Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell 2017, 170, 185– 198.e16, DOI: 10.1016/j.cell.2017.05.034253https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVOjtr7F&md5=88668aed566a2bfb515067b7dcda5789Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural PathwaysBellono, Nicholas W.; Bayrer, James R.; Leitch, Duncan B.; Castro, Joel; Zhang, Chuchu; O'Donnell, Tracey A.; Brierley, Stuart M.; Ingraham, Holly A.; Julius, DavidCell (Cambridge, MA, United States) (2017), 170 (1), 185-198.e16CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiol. processes ranging from metab. to cognition. The gut epithelium is a principal site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single-cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single-cell measurements to elucidate intrinsic biophys., pharmacol., and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are elec. excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.
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254Ye, L.; Bae, M.; Cassilly, C. D.; Jabba, S. V.; Thorpe, D. W.; Martin, A. M.; Lu, H. Y.; Wang, J.; Thompson, J. D.; Lickwar, C. R. Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways. Cell Host Microbe 2021, 29, 179– 196.e79, DOI: 10.1016/j.chom.2020.11.011254https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXktlajsw%253D%253D&md5=4abd750d5836a0e6f1b530180778294fEnteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathwaysYe, Lihua; Bae, Munhyung; Cassilly, Chelsi D.; Jabba, Sairam V.; Thorpe, Daniel W.; Martin, Alyce M.; Lu, Hsiu-Yi; Wang, Jinhu; Thompson, John D.; Lickwar, Colin R.; Poss, Kenneth D.; Keating, Damien J.; Jordt, Sven-Eric; Clardy, Jon; Liddle, Rodger A.; Rawls, John F.Cell Host & Microbe (2021), 29 (2), 179-196.e9CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility. Microbial, pharmacol., or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons by secreting the neurotransmitter 5-hydroxytryptamine (5-HT). A subset of indole derivs. of tryptophan catabolism produced by E. tarda and other gut microbes activates zebrafish EEC Trpa1 signaling. These catabolites also directly stimulate human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a mol. pathway by which EECs regulate enteric and vagal neuronal pathways in response to microbial signals.
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255O’Hagan, C.; Li, J. V.; Marchesi, J. R.; Plummer, S.; Garaiova, I.; Good, M. A. Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats. Neurobiol Learn Mem 2017, 144, 36– 47, DOI: 10.1016/j.nlm.2017.05.015255https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVGktr3J&md5=4ea879e2715e8e481dff3b0b7e02fa3eLong-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged ratsO'Hagan, Caroline; Li, Jia V.; Marchesi, Julian R.; Plummer, Sue; Garaiova, Iveta; Good, Mark A.Neurobiology of Learning and Memory (2017), 144 (), 36-47CODEN: NLMEFR; ISSN:1074-7427. (Elsevier Inc.)Ageing is assocd. with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and prodn. of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixt. (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioral flexibility in 15-17-mo-old male rats. Following behavioral testing, the hippocampus and prefrontal cortex was extd. and analyzed ex vivo using 1H NMR (1H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place assocns. Short-term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. 1H NMR anal. revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory.
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256Mao, J.-H.; Kim, Y.-M.; Zhou, Y.-X.; Hu, D.; Zhong, C.; Chang, H.; Brislawn, C. J.; Fansler, S.; Langley, S.; Wang, Y. Genetic and metabolic links between the murine microbiome and memory. Microbiome 2020, 8, 53, DOI: 10.1186/s40168-020-00817-w256https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjsVehsbs%253D&md5=90f020cfab898e7e8f0cc61b09ef752eGenetic and metabolic links between the murine microbiome and memoryMao, Jian-Hua; Kim, Young-Mo; Zhou, Yan-Xia; Hu, Dehong; Zhong, Chenhan; Chang, Hang; Brislawn, Colin J.; Fansler, Sarah; Langley, Sasha; Wang, Yunshan; Peisl, B. Y. Loulou; Celniker, Susan E.; Threadgill, David W.; Wilmes, Paul; Orr, Galya; Metz, Thomas O.; Jansson, Janet K.; Snijders, Antoine M.Microbiome (2020), 8 (1), 53CODEN: MICRMP; ISSN:2049-2618. (BioMed Central Ltd.)Recent evidence has linked the gut microbiome to host behavior via the gut-brain axis; however, the underlying mechanisms remain unexplored. A genome-wide assocn. anal. (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly assocd. with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a pos. correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics anal. revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice. Together, this study provides new evidence for a link between Lactobacillus and memory and the results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites.
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257El Hayek, L.; Khalifeh, M.; Zibara, V.; Abi Assaad, R.; Emmanuel, N.; Karnib, N.; El-Ghandour, R.; Nasrallah, P.; Bilen, M.; Ibrahim, P. Lactate Mediates the Effects of Exercise on Learning and Memory through SIRT1-Dependent Activation of Hippocampal Brain-Derived Neurotrophic Factor (BDNF). J. Neurosci. 2019, 39, 2369– 2382, DOI: 10.1523/JNEUROSCI.1661-18.2019257https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cjmtlSquw%253D%253D&md5=70eb44958e8732a7b2373388d184535fLactate Mediates the Effects of Exercise on Learning and Memory through SIRT1-Dependent Activation of Hippocampal Brain-Derived Neurotrophic Factor (BDNF)El Hayek Lauretta; Khalifeh Mohamad; Zibara Victor; Abi Assaad Rawad; Emmanuel Nancy; Karnib Nabil; El-Ghandour Rim; Nasrallah Patrick; Bilen Maria; Ibrahim Pascale; Younes Joe; Abou Haidar Edwina; Barmo Nour; Jabre Vanessa; Sleiman Sama F; Stephan Joseph SThe Journal of neuroscience : the official journal of the Society for Neuroscience (2019), 39 (13), 2369-2382 ISSN:.Exercise promotes learning and memory formation. These effects depend on increases in hippocampal BDNF, a growth factor associated with cognitive improvement and the alleviation of depression symptoms. Identifying molecules that are produced during exercise and that mediate hippocampal Bdnf expression will allow us to harness the therapeutic potential of exercise. Here, we report that an endogenous molecule produced during exercise in male mice induces the Mus musculus Bdnf gene and promotes learning and memory formation. The metabolite lactate, which is released during exercise by the muscles, crosses the blood-brain barrier and induces Bdnf expression and TRKB signaling in the hippocampus. Indeed, we find that lactate-dependent increases in BDNF are associated with improved spatial learning and memory retention. The action of lactate is dependent on the activation of the Sirtuin1 deacetylase. SIRT1 increases the levels of the transcriptional coactivator PGC1a and the secreted molecule FNDC5, known to mediate Bdnf expression. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF, and identify lactate as a potential endogenous molecule that may have therapeutic value for CNS diseases in which BDNF signaling is disrupted.SIGNIFICANCE STATEMENT It is established that exercise promotes learning and memory formation and alleviates the symptoms of depression. These effects are mediated through inducing Bdnf expression and signaling in the hippocampus. Understanding how exercise induces Bdnf and identifying the molecules that mediate this induction will allow us to design therapeutic strategies that can mimic the effects of exercise on the brain, especially for patients with CNS disorders characterized by a decrease in Bdnf expression and who cannot exercise because of their conditions. We identify lactate as an endogenous metabolite that is produced during exercise, crosses the blood-brain barrier and promotes hippocampal dependent learning and memory in a BDNF-dependent manner. Our work identifies lactate as a component of the "exercise pill."
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258Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nature Reviews Gastroenterology & Hepatology 2019, 16, 461– 478, DOI: 10.1038/s41575-019-0157-3258https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7pt1Witw%253D%253D&md5=1b468afb50257e2ad98b7cbfb80b7db1The role of short-chain fatty acids in microbiota-gut-brain communicationDalile Boushra; Van Oudenhove Lukas; Verbeke Kristin; Vervliet BramNature reviews. Gastroenterology & hepatology (2019), 16 (8), 461-478 ISSN:.Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.
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259van de Wouw, M.; Boehme, M.; Lyte, J. M.; Wiley, N.; Strain, C.; O’Sullivan, O.; Clarke, G.; Stanton, C.; Dinan, T. G.; Cryan, J. F. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. Journal of Physiology 2018, 596, 4923– 4944, DOI: 10.1113/JP276431259https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsF2lt7jP&md5=550e19112a53fb82de71611be6b0cac6Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterationsvan de Wouw, Marcel; Boehme, Marcus; Lyte, Joshua M.; Wiley, Niamh; Strain, Conall; O'Sullivan, Orla; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.Journal of Physiology (Oxford, United Kingdom) (2018), 596 (20), 4923-4944CODEN: JPHYA7; ISSN:1469-7793. (Wiley-Blackwell)Key points : Chronic (psychosocial) stress changes gut microbiota compn., as well as inducing behavioral and physiol. deficits. The study assess whether short-chain fatty acids (SCFAs) supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixt. of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 wk of repeated psychosocial stress, followed by a comprehensive behavioral anal. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota compn. were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behavior, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addn., SCFAs exhibited behavioral test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body wt. gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota compn. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.
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260Bernasconi, R.; Jones, R. S.; Bittiger, H.; Olpe, H. R.; Heid, J.; Martin, P.; Klein, M.; Loo, P.; Braunwalder, A.; Schmutz, M. Dose pipecolic acid interact with the central GABA-ergic system?. J. Neural Transm. 1986, 67, 175– 189, DOI: 10.1007/BF01243346260https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2sXps1Oqsg%253D%253D&md5=b357e9f578d1ab146212cc6b88e6278aDoes pipecolic acid interact with the central GABA-ergic system?Bernasconi, R.; Jones, R. S. G.; Bittiger, H.; Olpe, H. R.; Heid, J.; Martin, P.; Klein, M.; Loo, P.; Braunwalder, A.; Schmutz, M.Journal of Neural Transmission (1972-1989) (1986), 67 (3-4), 175-89CODEN: JNTMAH; ISSN:0300-9564.Several previous studies have suggested a strong GABA [56-12-2]-mimetic action of the endogenous brain imino acid L-pipecolic acid (PA) [3105-95-1]. These observations were evaluated by using electrophysiol. and neurochem. methods on rat cortical neurons in situ. In contrast to published data, only a weak, but bicuculline-sensitive depressant action of PA on cortical neurons was obsd. Furthermore, PA had no affinity for any of the 3 components of the GABA-benzodiazepine-Cl- channel receptor complex. However, in using a modification of published methods, a weak affinity for the GABA-B receptor site was demonstrated [concn. for 50% inhibition (IC50) = 1.8 × 10-3M]. PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15). PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. These results are not compatible with a strong in vivo interaction between PA and GABA-mediated inhibitory transmission.
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261Takahama, K.; Hashimoto, T.; Wang, M. W.; Akaike, N.; Hitoshi, T.; Okano, Y.; Kasé, Y.; Miyata, T. Pipecolic acid enhancement of GABA response in single neurons of rat brain. Neuropharmacology 1986, 25, 339– 342, DOI: 10.1016/0028-3908(86)90263-7261https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL28Xhs1anu7w%253D&md5=9daeb6c15ef8e55e338067a0ab7e0968Pipecolic acid enhancement of GABA response in single neurons of rat brainTakahama, K.; Hashimoto, T.; Wang, M. W.; Akaike, N.; Hitoshi, T.; Okano, Y.; Kase, Y.; Miyata, T.Neuropharmacology (1986), 25 (3), 339-42CODEN: NEPHBW; ISSN:0028-3908.Using unit recording and microelectrophoresis, the influence of pipecolic acid (PA) [535-75-1], a major metabolite of lysine in the brain, on GABA [56-12-2] and glycine [56-40-6] responses was studied in the cerebral cortical and hippocampal pyramidal neurons of rats. With small currents, PA had no effect on the single neuron activities but enhanced GABA response without affecting glycine response. Thus, PA may have a connection with central GABA system.
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262Braniste, V.; Al-Asmakh, M.; Kowal, C.; Anuar, F.; Abbaspour, A.; Tóth, M.; Korecka, A.; Bakocevic, N.; Ng, L. G.; Kundu, P. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 2014, 6, 263ra158– 263ra158, DOI: 10.1126/scitranslmed.3009759There is no corresponding record for this reference.
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263Li, H.; Sun, J.; Wang, F.; Ding, G.; Chen, W.; Fang, R.; Yao, Y.; Pang, M.; Lu, Z. Q.; Liu, J. Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice. Brain Res. 2016, 1642, 70– 78, DOI: 10.1016/j.brainres.2016.03.031263https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xlt1Snurc%253D&md5=910e9dfb5b484f26d1bd2f2140b3a31bSodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury miceLi, Haixiao; Sun, Jing; Wang, Fangyan; Ding, Guoqiang; Chen, Wenqian; Fang, Renchi; Yao, Ye; Pang, Mengqi; Lu, Zhong-Qiu; Liu, JiamingBrain Research (2016), 1642 (), 70-78CODEN: BRREAP; ISSN:0006-8993. (Elsevier B.V.)Sodium butyrate (SB) has been widely used to treat cerebral diseases. The aim of the present study is to examine the neuroprotective effects of SB on early TBI in mice and to explore the underlying mechanisms of these effects. TBI was induced using a modified wt.-drop method. Neurol. deficits were evaluated according to the neurol. severity score (NSS), brain edema was measured by brain water content, and blood-brain barrier (BBB) permeability was evaluated by Evans blue (EB) dye extravasation. Neuronal injury was assessed by hematoxylin and eosin (H&E) staining and Fluoro-Jade C staining. The expression of tight junction-assocd. proteins, such as occludin and zonula occludens-1 (ZO-1), was analyzed by western blotting and immunofluorescence. Our results showed that mice subjected to TBI exhibited worsened NSS, brain edema, neuronal damage and BBB permeability. However, these were all attenuated by SB. Moreover, SB reversed the decrease in occludin and ZO-1 expression induced by TBI. These findings suggest that SB might attenuate neurol. deficits, brain edema, neuronal change and BBB damage, as well as increase occludin and ZO-1 expression in the brain to protect against TBI. The protective effect of SB may be correlated with restoring the BBB following its impairment.
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264Hoyles, L.; Snelling, T.; Umlai, U.-K.; Nicholson, J. K.; Carding, S. R.; Glen, R. C.; McArthur, S. Microbiome–host systems interactions: protective effects of propionate upon the blood–brain barrier. Microbiome 2018, 6, 55, DOI: 10.1186/s40168-018-0439-y264https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MnjsVyrtw%253D%253D&md5=37554bb850a120a8702d86617f653e97Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrierHoyles Lesley; Snelling Tom; Umlai Umm-Kulthum; Nicholson Jeremy K; Glen Robert C; Carding Simon R; Carding Simon R; Glen Robert C; McArthur SimonMicrobiome (2018), 6 (1), 55 ISSN:.BACKGROUND: Gut microbiota composition and function are symbiotically linked with host health and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, and the blood-brain barrier (BBB) also contribute to the gut-brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed. RESULTS: After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signalling. CONCLUSIONS: Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut-brain axis that warrants further attention.
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265Quinn, M.; McMillin, M.; Galindo, C.; Frampton, G.; Pae, H. Y.; DeMorrow, S. Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms. Dig. Liver Dis. 2014, 46, 527– 534, DOI: 10.1016/j.dld.2014.01.159265https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksFWqsbg%253D&md5=9d94f4f86f1d08329d3e0bea7067acf6Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanismsQuinn, Matthew; McMillin, Matthew; Galindo, Cheryl; Frampton, Gabriel; Pae, Hae Yong; DeMorrow, SharonDigestive and Liver Disease (2014), 46 (6), 527-534CODEN: DLDIFK; ISSN:1590-8658. (Elsevier B.V.)The blood brain barrier tightly regulates the passage of mols. into the brain and becomes leaky following obstructive cholestasis. The aim of this study was to det. if increased serum bile acids obsd. during cholestasis permeabilize the blood brain barrier. Rats underwent bile duct ligation or deoxycholic or chenodeoxycholic acid injections and blood brain barrier permeability assessed. In vitro, the permeability of rat brain microvessel endothelial cell monolayers, the expression and phosphorylation of occludin, ZO-1 and ZO-2 as well as the activity of Rac1 was assessed after treatment with plasma from cholestatic rats, or bile acid treatment, in the presence of a Rac1 inhibitor. Blood brain barrier permeability was increased in vivo and in vitro following bile duct ligation or treatment with bile acids. Assocd. with the bile acid-stimulated increase in endothelial cell monolayer permeability was elevated Rac1 activity and increased phosphorylation of occludin. Pretreatment of endothelial cell monolayers with a Rac1 inhibitor prevented the effects of bile acid treatment on occludin phosphorylation and monolayer permeability. These data suggest that increased circulating serum bile acids may contribute to the increased permeability of the blood brain barrier seen during obstructive cholestasis via disruption of tight junctions.
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266Palmela, I.; Correia, L.; Silva, R. F. M.; Sasaki, H.; Kim, K. S.; Brites, D.; Brito, M. A. Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study. Front. Neurosci. 2015, 9, 80, DOI: 10.3389/fnins.2015.00080266https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2Mnpt1SjsA%253D%253D&md5=9b3c6fabb43315c5be8406d37695a53cHydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro studyPalmela Ines; Correia Leonor; Silva Rui F M; Brites Dora; Brito Maria A; Sasaki Hiroyuki; Kim Kwang SFrontiers in neuroscience (2015), 9 (), 80 ISSN:1662-4548.Ursodeoxycholic acid and its main conjugate glycoursodeoxycholic acid are bile acids with neuroprotective properties. Our previous studies demonstrated their anti-apoptotic, anti-inflammatory, and antioxidant properties in neural cells exposed to elevated levels of unconjugated bilirubin (UCB) as in severe jaundice. In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular endothelial cells, UCB has shown to induce caspase-3 activation and cell death, as well as interleukin-6 release and a loss of blood-brain barrier integrity. Here, we tested the preventive and restorative effects of these bile acids regarding the disruption of blood-brain barrier properties by UCB in in vitro conditions mimicking severe neonatal hyperbilirubinemia and using the same experimental blood-brain barrier model. Both bile acids reduced the apoptotic cell death induced by UCB, but only glycoursodeoxycholic acid significantly counteracted caspase-3 activation. Bile acids also prevented the upregulation of interleukin-6 mRNA, whereas only ursodeoxycholic acid abrogated cytokine release. Regarding barrier integrity, only ursodeoxycholic acid abrogated UCB-induced barrier permeability. Better protective effects were obtained by bile acid pre-treatment, but a strong efficacy was still observed by their addition after UCB treatment. Finally, both bile acids showed ability to cross confluent monolayers of human brain microvascular endothelial cells in a time-dependent manner. Collectively, data disclose a therapeutic time-window for preventive and restorative effects of ursodeoxycholic acid and glycoursodeoxycholic acid against UCB-induced blood-brain barrier disruption and damage to human brain microvascular endothelial cells.
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267Hoyles, L.; Pontifex, M. G.; Rodriguez-Ramiro, I.; Anis-Alavi, M. A.; Jelane, K. S.; Snelling, T.; Solito, E.; Fonseca, S.; Carvalho, A. L.; Carding, S. R. Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide. Microbiome 2021, 9, 235, DOI: 10.1186/s40168-021-01181-z267https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjsVChtLo%253D&md5=469ad302a3b94bbc45f69521cabcbd54Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxideHoyles, Lesley; Pontifex, Matthew G.; Rodriguez-Ramiro, Ildefonso; Anis-Alavi, M. Areeb; Jelane, Khadija S.; Snelling, Tom; Solito, Egle; Fonseca, Sonia; Carvalho, Ana L.; Carding, Simon R.; Muller, Michael; Glen, Robert C.; Vauzour, David; McArthur, SimonMicrobiome (2021), 9 (1), 235CODEN: MICRMP; ISSN:2049-2618. (BioMed Central Ltd.)Communication between the gut microbiota and the brain is primarily mediated via sol. microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metab. of dietary choline and L-carnitine have received attention due to their proposed assocn. with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. Here, we use an integrated in vitro/in vivo approach to show that physiol. relevant concns. of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. Our findings demonstrate the mechanisms through which microbiome-assocd. methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function.
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268Magistretti, P. J.; Allaman, I. A cellular perspective on brain energy metabolism and functional imaging. Neuron 2015, 86, 883– 901, DOI: 10.1016/j.neuron.2015.03.035268https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXpt1Snu7w%253D&md5=7bf55bdc98f4e3aa87f2abdcd469a04bA Cellular Perspective on Brain Energy Metabolism and Functional ImagingMagistretti, Pierre J.; Allaman, IgorNeuron (2015), 86 (4), 883-901CODEN: NERNET; ISSN:0896-6273. (Cell Press)The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is assocd. with an increased glucose utilization and expression of energy metab. genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technol. advances in metabolic studies with cellular resoln. have afforded decisive insights into the understanding of the cellular and mol. bases of the coupling between neuronal activity and energy metab. and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metab. across resoln. scales.
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269Wyss, M. T.; Jolivet, R.; Buck, A.; Magistretti, P. J.; Weber, B. In Vivo Evidence for Lactate as a Neuronal Energy Source. J. Neurosci. 2011, 31, 7477– 7485, DOI: 10.1523/JNEUROSCI.0415-11.2011269https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmvFektLk%253D&md5=0be6e0e78737d934d61b108b3cca336dIn vivo evidence for lactate as a neuronal energy sourceWyss, Matthias T.; Jolivet, Renaud; Buck, Alfred; Magistretti, Pierre J.; Weber, BrunoJournal of Neuroscience (2011), 31 (20), 7477-7485CODEN: JNRSDS; ISSN:0270-6474. (Society for Neuroscience)Cerebral energy metab. is a highly compartmentalized and complex process in which transcellular trafficking of metabolites plays a pivotal role. Over the past decade, a role for lactate in fueling the energetic requirements of neurons has emerged. Furthermore, a neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported. The majority of the current evidence concerning lactate metab. at the cellular level is based on in vitro data; only a few recent in vivo results have demonstrated that the brain preferentially utilizes lactate over glucose. Using voltage-sensitive dye (VSD) imaging, beta-probe measurements of radiotracer kinetics, and brain activation by sensory stimulation in the anesthetized rat, we investigated several aspects of cerebral lactate metab. The present study is the first in vivo demonstration of the maintenance of neuronal activity in the presence of lactate as the primary energy source. The loss of the voltage-sensitive dye signal found during severe insulin-induced hypoglycemia is completely prevented by lactate infusion. Thus, lactate has a direct neuroprotective effect. Furthermore, we demonstrate that the brain readily oxidizes lactate in an activity-dependent manner. The washout of 1-[11C]L-lactate, reflecting cerebral lactate oxidn., was obsd. to increase during brain activation from 0.077 ± 0.009 to 0.105 ± 0.007 min-1. Finally, our data confirm that the brain prefers lactate over glucose as an energy substrate when both substrates are available. Using [18F]fluorodeoxyglucose (FDG) to measure the local cerebral metabolic rate of glucose, we demonstrated a lactate concn.-dependent redn. of cerebral glucose utilization during exptl. increased plasma lactate levels.
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270Liu, Z.; Dai, X.; Zhang, H.; Shi, R.; Hui, Y.; Jin, X.; Zhang, W.; Wang, L.; Wang, Q.; Wang, D. Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat. Commun. 2020, 11, 855, DOI: 10.1038/s41467-020-14676-4270https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvFaju7g%253D&md5=baf7abe48bb0c1b76b754d056b8b6f0fGut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairmentLiu, Zhigang; Dai, Xiaoshuang; Zhang, Hongbo; Shi, Renjie; Hui, Yan; Jin, Xin; Zhang, Wentong; Wang, Luanfeng; Wang, Qianxu; Wang, Danna; Wang, Jia; Tan, Xintong; Ren, Bo; Liu, Xiaoning; Zhao, Tong; Wang, Jiamin; Pan, Junru; Yuan, Tian; Chu, Chuanqi; Lan, Lei; Yin, Fei; Cadenas, Enrique; Shi, Lin; Zhao, Shancen; Liu, XueboNature Communications (2020), 11 (1), 855CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metab. gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are obsd. between IF affected genes, microbiota and metabolites, as assessed by integrative modeling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metab.-implicated cognitive pathophysiologies.
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271Russell, W. R.; Hoyles, L.; Flint, H. J.; Dumas, M. E. Colonic bacterial metabolites and human health. Curr. Opin. Microbiol. 2013, 16, 246– 254, DOI: 10.1016/j.mib.2013.07.002271https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFGmu7nE&md5=4cee9b9ceb1c0f330914643a1cb9eaf7Colonic bacterial metabolites and human healthRussell, Wendy R.; Hoyles, Lesley; Flint, Harry J.; Dumas, Marc-EmmanuelCurrent Opinion in Microbiology (2013), 16 (3), 246-254CODEN: COMIF7; ISSN:1369-5274. (Elsevier Ltd.)A review. The influence of the microbial-mammalian metabolic axis is becoming increasingly important for human health. Bacterial fermn. of carbohydrates (CHOs) and proteins produces short-chain fatty acids (SCFA) and a range of other metabolites including those from arom. amino acid (AAA) fermn. SCFA influence host health as energy sources and via multiple signalling mechanisms. Bacterial transformation of fiber-related phytochems. is assocd. with a reduced incidence of several chronic diseases. The 'gut-liver axis' is an emerging area of study. Microbial deconjugation of xenobiotics and release of arom. moieties into the colon can have a wide range of physiol. consequences. In addn., the role of the gut microbiota in choline deficiency in non-alc. fatty liver disease (NAFLD) and insulin resistance is receiving increased attention.
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272Ren, Z.; Zhang, R.; Li, Y.; Li, Y.; Yang, Z.; Yang, H. Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo. Int. J. Mol. Med. 2017, 40, 1444– 1456, DOI: 10.3892/ijmm.2017.3127272https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOru77I&md5=dddc5fbf640e21cdd583d583e1bdecafFerulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivoRen, Zhongkun; Zhang, Rongping; Li, Yuanyuan; Li, Yu; Yang, Zhiyong; Yang, HuiInternational Journal of Molecular Medicine (2017), 40 (5), 1444-1456CODEN: IJMMFG; ISSN:1791-244X. (Spandidos Publications Ltd.)Ferulic acid (FA) is a deriv. of cinnamic acid. It is used in the treatment of heart head blood-vessel disease and exerts protective effects against hypoxia/ischemiainduced cell injury in the brain. This study investigated the potential neuroprotective effects of FA against ischemia/reperfusion (I/R)-induced brain injury in vivo and in vitro through hematoxylin and eosin (H&E) and Nissl staining assays, flow cytometry, Hoechst 33258 staining, quant. PCR, western blot anal. and fluorescence microscopic anal. In this study, models of cerebral I/R injury were established using rats and pheochromocytoma (PC-12) cells. The results revealed that treatment with FA significantly attenuated memory impairment, and reduced hippocampal neuronal apoptosis and oxidative stress in a dose-dependent manner. The results from in vitro expts. also indicated that FA protected the PC-12 cells against I/R-induced reactive oxygen species (ROS) generation and apoptosis by inhibiting apoptosis, Ca2+ influx, superoxide anion (O2-), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) prodn. in a concn.-dependent manner. Moreover, FA inactivated the Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway. MyD88 overexpression abolished the neuroprotective effects of FA. On the whole, we found that FA attenuated memory dysfunction and exerted protective effects against oxidative stress and apoptosis induced by I/R injury by inhibiting the TLR4/MyD88 signaling pathway. This study supports the view that FA may be a promising neuroprotective agent for use in the treatment of cerebral ischemia.
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273Zeni, A. L. B.; Camargo, A.; Dalmagro, A. P. Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice. Steroids 2017, 125, 131– 136, DOI: 10.1016/j.steroids.2017.07.006273https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1enur%252FO&md5=10737f509116132ad93f8b214023939bFerulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in miceZeni, Ana Lucia Bertarello; Camargo, Anderson; Dalmagro, Ana PaulaSteroids (2017), 125 (), 131-136CODEN: STEDAM; ISSN:0039-128X. (Elsevier)Corticosterone (CORT) treatment has been evidenced to develop a depression-like state in animals, that mimic hypothalamic-pituitary-adrenal (HPA)-axis dysregulation implicated in the development of depression. The present study aimed to examine the ferulic acid (FA), a natural phenolic compd., antidepressant and antioxidant activities on the CORT chronic model. Mice orally treated with 20 mg/kg of CORT for 21 days were considered control group, while mice treated with FA (1 mg/kg) or fluoxetine (10 mg/kg) for the last week of CORT treatment, as drug groups. Three weeks of CORT treatment resulted in depressive-like behavior, as indicated by the increase on the immobility time in the tail suspension test, grooming in the splash test and an increase in the oxidative stress markers in the brain. It was obsd. that FA ameliorated the behavioral and oxidative stress alterations induced by CORT, which may plausibly suggest a mode of action for the FA antidepressant effect. The involvement of FA repairing the stress caused by HPA-axis dysfunction evidenced that this phenolic acid could be further investigated as a novel potential agent to improve the management of depression.
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274Verzelloni, E.; Pellacani, C.; Tagliazucchi, D.; Tagliaferri, S.; Calani, L.; Costa, L. G.; Brighenti, F.; Borges, G.; Crozier, A.; Conte, A. Antiglycative and neuroprotective activity of colon-derived polyphenol catabolites. Mol. Nutr. Food Res. 2011, 55, S35– S43, DOI: 10.1002/mnfr.201000525274https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFSltL%252FP&md5=adb4a1bb4d6f2975226d86847520f2f6Antiglycative and neuroprotective activity of colon-derived polyphenol catabolitesVerzelloni, Elena; Pellacani, Claudia; Tagliazucchi, Davide; Tagliaferri, Sara; Calani, Luca; Costa, Lucio G.; Brighenti, Furio; Borges, Gina; Crozier, Alan; Conte, Angela; Del Rio, DanieleMolecular Nutrition & Food Research (2011), 55 (Suppl. 1), S35-S43CODEN: MNFRCV; ISSN:1613-4125. (Wiley-VCH Verlag GmbH & Co. KGaA)Scope: Dietary flavonoids and allied phenolic compds. are thought to be beneficial in the control of diabetes and its complications, because of their ability to inhibit oxidative stress, protein glycation and to act as neuroprotectants. Following ingestion by humans, polyphenolic compds. entering the large intestine undergo extensive metab. by interaction with colonic microbiota and it is metabolites and catabolites of the parent compds. that enter the circulatory system. The aim of this study was to investigate the inhibitory activity of some colonic microbiota-derived polyphenol catabolites against advanced glycation endproducts formation in vitro and to det. their ability, at physiol. concns., to counteract mild oxidative stress of cultured human neuron cells. Methods and results: This study demonstrated that ellagitannin-derived catabolites (urolithins and pyrogallol) are the most effective antiglycative agents, whereas chlorogenic acid-derived catabolites (dihydrocaffeic acid, dihydroferulic acid and feruloylglycine) were most effective in combination in protecting neuronal cells in a conservative in vitro exptl. model. Conclusion: Some polyphenolic catabolites, generated in vivo in the colon, were able in vitro to counteract two key features of diabetic complications, i.e. protein glycation and neurodegeneration. These observations could lead to a better control of these events, which are usually correlated with hyperglycemia.
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275Macfarlane, S.; Macfarlane, G. T. Regulation of short-chain fatty acid production. Proc. Nutr. Soc. 2003, 62, 67– 72, DOI: 10.1079/PNS2002207275https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXjslyhtLc%253D&md5=eae7e43433cdbec5bc8b1f3bb3ef482eSession: Short-chain fatty acids. Regulation of short-chain fatty acid productionMacfarlane, Sandra; Macfarlane, Georgia T.Proceedings of the Nutrition Society (2003), 62 (1), 67-72CODEN: PNUSA4; ISSN:0029-6651. (CABI Publishing)A review. Short-chain fatty acid (SCFA) formation by intestinal bacteria is regulated by many different host, environmental, dietary, and microbiol. factors. Substrate availability, bacterial species compn. of the intestinal microflora, and intestinal transit time largely det. the amts. and types of SCFA produced in healthy individuals. Most SCFA in the gut are derived from bacterial breakdown of complex dietary carbohydrates, esp. in the proximal bowel, but digestion of proteins and peptides makes an increasing contribution to SCFA prodn. as food residues pass through the bowel. Bacterial hydrogen metab. also affects the way in which SCFA are made. This can be seen through the effects of inorg. electron acceptors (nitrate, sulfate) on fermn. processes, where they facilitate the formation of more oxidized SCFA such as acetate, at the expense of more reduced fatty acids, such as butyrate. Chemostat studies with pure cultures of saccharolytic gut microorganisms show that carbon availability and growth rate strongly affect the outcome of fermn. Acetate and formate are the major bifidobacterial fermn. products formed during growth under carbon sources limitation, whereas acetate and lactate are produced when carbohydrate is in excess. Lactate is also used as an electron sink in Clostridium perfringens and, to a lesser extent, in Bacteroides fragilis. In the latter microorganism, acetate and succinate are the major fermn. products when substrate is abundant, whereas succinate is decarboxylated to propionate when carbon and energy sources are limiting.
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276Thomas, C. M.; Hong, T.; van Pijkeren, J. P.; Hemarajata, P.; Trinh, D. V.; Hu, W.; Britton, R. A.; Kalkum, M.; Versalovic, J. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One 2012, 7, e31951, DOI: 10.1371/journal.pone.0031951276https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjsVejtbw%253D&md5=c53235a29e18762b542e36e29688a2c5Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signalingThomas, Carissa M.; Hong, Teresa; van Pijkeren, Jan Peter; Hemarajata, Peera; Trinh, Dan V.; Hu, Weidong; Britton, Robert A.; Kalkum, Markus; Versalovic, JamesPLoS One (2012), 7 (2), e31951CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biol. active compds. that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compd.(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liq. chromatog.-high performance liq. chromatog. (HILIC-HPLC) sepn. isolated TNF-inhibitory compds., and HILIC-HPLC fraction compn. was detd. by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from -histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in prodn. of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF prodn. via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF prodn. by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, -histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF prodn. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases.
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277De Biase, D.; Pennacchietti, E. Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operon. Mol. Microbiol. 2012, 86, 770– 786, DOI: 10.1111/mmi.12020277https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFyqsrk%253D&md5=fbe249895db7344d75729f206fb33ee1Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: function, distribution and biomedical implications of the gadBC operonDe Biase, Daniela; Pennacchietti, EugeniaMolecular Microbiology (2012), 86 (4), 770-786CODEN: MOMIEE; ISSN:0950-382X. (Wiley-Blackwell)A review. For successful colonization of the mammalian host, orally acquired bacteria must overcome the extreme acidic stress (pH < 2.5) encountered during transit through the host stomach. The glutamate-dependent acid resistance (GDAR) system is by far the most potent acid resistance system in commensal and pathogenic Escherichia coli, Shigella flexneri, Listeria monocytogenes and Lactococcus lactis. GDAR requires the activity of glutamate decarboxylase (GadB), an intracellular PLP-dependent enzyme which performs a proton-consuming decarboxylation reaction, and of the cognate antiporter (GadC), which performs the glutamatein/γ-aminobutyrateout (GABA) electrogenic antiport. Here, the authors review recent findings on the structural determinants responsible for pH-dependent intracellular activation of E. coli GadB and GadC. A survey of genomes of bacteria (pathogenic and non-pathogenic), having in common the ability to colonize or to transit through the host gut, shows that the gadB and gadC genes frequently lie next or near each other. This gene arrangement is likely to be important to ensure timely co-regulation of the decarboxylase and the antiporter. Besides the involvement in acid resistance, GABA prodn. and release were found to occur at very high levels in lactic acid bacteria originally isolated from traditionally fermented foods, supporting the evidence that GABA-enriched foods possess health-promoting properties.
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278Zhou, L.; Zeng, Y.; Zhang, H.; Ma, Y. The Role of Gastrointestinal Microbiota in Functional Dyspepsia: A Review. Front. Physiol. 2022, 13, 910568, DOI: 10.3389/fphys.2022.910568278https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MfgsFylsA%253D%253D&md5=aaaf7f23983276192a7afe1dd6083e06The Role of Gastrointestinal Microbiota in Functional Dyspepsia: A ReviewZhou Li; Ma Yan; Zeng Yi; Zhang HongxingFrontiers in physiology (2022), 13 (), 910568 ISSN:1664-042X.Functional dyspepsia is a clinically common functional gastrointestinal disorder with a high prevalence, high impact and high consumption of medical resources. The microbiota in the gastrointestinal tract is a large number of families and is one of the most complex microbial reservoirs in the human body. An increasing number of studies have confirmed the close association between dysbiosis of the gastrointestinal microbiota and the occurrence and progression of functional dyspepsia. Therefore, we reviewed the role of dysbiosis of the gastrointestinal microbiota, H. pylori infection and gastrointestinal microbiota metabolites in functional dyspepsia, focusing on the possible mechanisms by which dysbiosis of the gastrointestinal microbiota contributes to the pathogenesis of functional dyspepsia. Several studies have confirmed that dysbiosis of the gastrointestinal microbiota may cause the occurrence and progression of functional dyspepsia by disrupting the biological barrier of the intestinal mucosa, by disturbing the immune function of the intestinal mucosa, or by causing dysregulation of the microbial-gut-brain axis. Probiotics and antibiotics have also been chosen to treat functional dyspepsia in clinical studies and have shown some improvement in the clinical symptoms. However, more studies are needed to explore and confirm the relationship between dysbiosis of the gastrointestinal microbiota and the occurrence and progression of functional dyspepsia, and more clinical studies are needed to confirm the therapeutic efficacy of microbiota modulation for functional dyspepsia.
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279Alexandrov, P. N.; Hill, J. M.; Zhao, Y.; Bond, T.; Taylor, C. M.; Percy, M. E.; Li, W.; Lukiw, W. J. Aluminum-induced generation of lipopolysaccharide (LPS) from the human gastrointestinal (GI)-tract microbiome-resident Bacteroides fragilis. J. Inorg. Biochem. 2020, 203, 110886, DOI: 10.1016/j.jinorgbio.2019.110886279https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFGqsbvE&md5=29d04279adbb1aeb6db878f1517cac28Aluminum-induced generation of lipopolysaccharide (LPS) from the human gastrointestinal (GI)-tract microbiome-resident Bacteroides fragilisAlexandrov, P. N.; Hill, J. M.; Zhao, Y.; Bond, T.; Taylor, C. M.; Percy, M. E.; Li, W.; Lukiw, W. J.Journal of Inorganic Biochemistry (2020), 203 (), 110886CODEN: JIBIDJ; ISSN:0162-0134. (Elsevier)Gram-neg. bacteria of the human gastrointestinal (GI) tract microbiome: (i) are capable of generating a broad-spectrum of highly neurotoxic, pro-inflammatory and potentially pathogenic mols.; and (ii) these include a highly immunogenic class of amphipathic surface glycolipids known as lipopolysaccharide (LPS). Bacteroides fragilis (B. fragilis), a commensal, Gram neg., non-motile, non-spore forming obligatory anaerobic bacillus, and one of the most abundant bacteria found in the human GI tract, produces a particularly pro-inflammatory and neurotoxic LPS (BF-LPS). BF-LPS: (i) is known to be secreted from the B. fragilis outer membrane into the external-medium; (ii) can damage biophysiol. barriers via cleavage of zonula adherens cell-cell adhesion proteins, thereby disrupting both the GI-tract barrier and the blood-brain barrier (BBB); (iii) is able to transit GI-tract barriers into the systemic circulation and cross the BBB into the human CNS; and (iv) accumulates within CNS neurons in neurodegenerative disorders such as Alzheimer's disease (AD). This short communication provides evidence that the incubation of B. fragilis with aluminum sulfate [Al2(SO4)3] is a potent inducer of BF-LPS. The results suggest for the first time that the pro-inflammatory properties of aluminum may not only be propagated by aluminum itself, but by a stimulation in the prodn. of microbiome-derived BF-LPS and other pro-inflammatory pathogenic microbial products normally secreted from human GI-tract-resident microorganisms.
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280Brown, E. M.; Ke, X.; Hitchcock, D.; Jeanfavre, S.; Avila-Pacheco, J.; Nakata, T.; Arthur, T. D.; Fornelos, N.; Heim, C.; Franzosa, E. A. Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis. Cell Host Microbe 2019, 25, 668– 680.e67, DOI: 10.1016/j.chom.2019.04.002280https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXptFCjsb8%253D&md5=9066af01c7cbaffe9d96bb1c2f9aaf37Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and SymbiosisBrown, Eric M.; Ke, Xiaobo; Hitchcock, Daniel; Jeanfavre, Sarah; Avila-Pacheco, Julian; Nakata, Toru; Arthur, Timothy D.; Fornelos, Nadine; Heim, Cortney; Franzosa, Eric A.; Watson, Nicki; Huttenhower, Curtis; Haiser, Henry J.; Dillow, Glen; Graham, Daniel B.; Finlay, B. Brett; Kostic, Aleksandar D.; Porter, Jeffrey A.; Vlamakis, Hera; Clish, Clary B.; Xavier, Ramnik J.Cell Host & Microbe (2019), 25 (5), 668-680.e7CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)Sphingolipids are structural membrane components and important eukaryotic signaling mols. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentially abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipids, but the impact of these metabolites on host pathways is largely uncharacterized. To det. whether bacterial sphingolipids modulate intestinal health, we colonized germ-free mice with a sphingolipid-deficient Bacteroides thetaiotaomicron strain. A lack of Bacteroides-derived sphingolipids resulted in intestinal inflammation and altered host ceramide pools in mice. Using lipidomic anal., we described a sphingolipid biosynthesis pathway and revealed a variety of Bacteroides-derived sphingolipids including ceramide phosphoinositol and deoxy-sphingolipids. Annotating Bacteroides sphingolipids in an IBD metabolomic dataset revealed lower abundances in IBD and neg. correlations with inflammation and host sphingolipid prodn. These data highlight the role of bacterial sphingolipids in maintaining homeostasis and symbiosis in the gut.
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281Gao, K.; Pi, Y.; Mu, C. L.; Farzi, A.; Liu, Z.; Zhu, W. Y. Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota-brain axis. J. Neurochem. 2019, 149, 641– 659, DOI: 10.1111/jnc.14709281https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXpsFagu70%253D&md5=5c44d1a907a9a89e54e338ac136a4b92Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: aromatic amino acids linking the microbiota-brain axisGao, Kan; Pi, Yu; Mu, Chun-Long; Farzi, Aitak; Liu, Zhuang; Zhu, Wei-YunJournal of Neurochemistry (2019), 149 (5), 641-659CODEN: JONRA9; ISSN:0022-3042. (Wiley-Blackwell)The gut microbiota is increasingly recognized to modulate brain function by recent studies demonstrating the central effects of various gut microbial manipulation strategies. Our previous study demonstrated that antibiotic-induced alterations of hindgut microbiota are assocd. with changes in arom. amino acid (AAA) metab. and hypothalamic neurochem., while the underlying mechanistic insight is limited. Given that the microbial AAA metab. can be affected by luminal carbohydrate availability, here we hypothesize that increasing hindgut carbohydrate availability affects the expression of neurotransmitters in the porcine hypothalamus. A hindgut microbiota-targeted strategy was adopted by increasing hindgut carbohydrate availability in a cecal-cannulated piglet model. Mechanistic involvement of AAAs along the gut microbiota-brain axis was further investigated in mice and neuronal cells. Increasing carbohydrate availability by cecal starch infusion led to a decrease in hindgut AAA metab., and an increase in systemic AAA availability, central AAA-derived neurotransmitters (5-HT, dopamine), and neurotrophin BDNF in piglets, indicating that hindgut microbiota affect hypothalamic neurochem. in an AAA-dependent manner. Single AAA i.p. injection in mice revealed that an increase in circulating tryptophan and tyrosine elevated their concns. in brain and finally promoted the expressions of 5-HT, dopamine, and BDNF in a time-dependent manner. Neuronal cells treated with single AAAs in vitro further demonstrated that tryptophan and tyrosine enhanced 5-HT and dopamine synthesis, resp., and promoted BDNF expression partly through the 5-HT1A/DRD1-CREB pathway. Our study reveals that increasing hindgut carbohydrate availability promotes hypothalamic neurotransmitter synthesis and that AAAs act as potential mediators between hindgut microbiota and brain neurochem.
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282Gao, K.; Mu, C.-l.; Farzi, A.; Zhu, W.-y. Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. Adv. Nutr. 2020, 11, 709– 723, DOI: 10.1093/advances/nmz127282https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MfovFarug%253D%253D&md5=517971632b0589cd171716d960b396a5Tryptophan Metabolism: A Link Between the Gut Microbiota and BrainGao Kan; Mu Chun-Long; Zhu Wei-Yun; Gao Kan; Mu Chun-Long; Zhu Wei-Yun; Farzi AitakAdvances in nutrition (Bethesda, Md.) (2020), 11 (3), 709-723 ISSN:.The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota. We start by outlining existing knowledge on tryptophan metabolism, including serotonin synthesis and degradation pathways of the host, and summarize recent advances in demonstrating the influence of the gut microbiota on tryptophan metabolism. The latest evidence revealing those mechanisms by which the gut microbiota modulates tryptophan metabolism, with subsequent effects on brain function, is reviewed. Finally, the potential modulation of intestinal tryptophan metabolism as a therapeutic option for brain and GI functional disorders is also discussed.
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283Xiao, L.; Liu, Q.; Luo, M.; Xiong, L. Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome. Frontiers in Cellular and Infection Microbiology 2021, 11, 729346, DOI: 10.3389/fcimb.2021.729346283https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XmslWrtrc%253D&md5=59c88c713d2413d27736a3a03283af9fGut microbiota-derived metabolites in irritable bowel syndromeXiao, Lin; Liu, Qin; Luo, Mei; Xiong, LishouFrontiers in Cellular and Infection Microbiology (2021), 11 (), 729346CODEN: FCIMAB; ISSN:2235-2988. (Frontiers Media S.A.)Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is assocd. with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiol. remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiol. factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, esp. bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.
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284Mawe, G. M.; Hoffman, J. M. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 473– 486, DOI: 10.1038/nrgastro.2013.105284https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1amtLrN&md5=d844a1824e6d6e186e3cb5ad4701cf4bSerotonin signalling in the gut-functions, dysfunctions and therapeutic targetsMawe, Gary M.; Hoffman, Jill M.Nature Reviews Gastroenterology & Hepatology (2013), 10 (8), 473-486CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. Serotonin (5-HT) has been recognized for decades as an important signalling mol. in the gut, but it is still revealing its secrets. Novel gastrointestinal functions of 5-HT continue to be discovered, as well as distant actions of gut-derived 5-HT, and we are learning how 5-HT signalling is altered in gastrointestinal disorders. Conventional functions of 5-HT involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion and vasodilation. Activation of extrinsic vagal and spinal afferent fibers results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts nonconventional actions such as promoting inflammation and serving as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, originating in the gut, promotes haemostasis, influences bone development and serves many other functions. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhoea or constipation, resp., and the synthetic enzyme tryptophan hydroxylase has also been targeted. Emerging evidence suggests that exploiting epithelial targets with nonabsorbable serotonergic agents could provide safe and effective therapies. We provide an overview of these serotonergic actions and treatment strategies.
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285Tan, J.; McKenzie, C.; Potamitis, M.; Thorburn, A. N.; Mackay, C. R.; Macia, L. The role of short-chain fatty acids in health and disease. Adv. Immunol. 2014, 121, 91– 119, DOI: 10.1016/B978-0-12-800100-4.00003-9285https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmslyitbc%253D&md5=406b18dd24f999e71d0043c09c9f0b73The role of short-chain fatty acids in health and diseaseTan, Jian; McKenzie, Craig; Potamitis, Maria; Thorburn, Alison N.; MacKay, Charles R.; Macia, LaurenceAdvances in Immunology (2014), 121 (), 91-119CODEN: ADIMAV; ISSN:0065-2776. (Elsevier Inc.)A review. There is now an abundance of evidence to show that short-chain fatty acids (SCFAs) play an important role in the maintenance of health and the development of disease. SCFAs are a subset of fatty acids that are produced by the gut microbiota during the fermn. of partially and nondigestible polysaccharides. The highest levels of SCFAs are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream. Two major SCFA signaling mechanisms have been identified, inhibition of histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs). Since HDACs regulate gene expression, inhibition of HDACs has a vast array of downstream consequences. Our understanding of SCFA-mediated inhibition of HDACs is still in its infancy. GPCRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have implicated a major role for these GPCRs in the regulation of metab., inflammation, and disease. SCFAs have been shown to alter chemotaxis and phagocytosis; induce reactive oxygen species (ROS); change cell proliferation and function; have anti-inflammatory, antitumorigenic, and antimicrobial effects; and alter gut integrity. These findings highlight the role of SCFAs as a major player in maintenance of gut and immune homeostasis. Given the vast effects of SCFAs, and that their levels are regulated by diet, they provide a new basis to explain the increased prevalence of inflammatory disease in Westernized countries, as highlighted in this chapter.
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286Felizardo, R. J. F.; Watanabe, I. K. M.; Dardi, P.; Rossoni, L. V.; Câmara, N. O. S. The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids. Pharmacol. Res. 2019, 141, 366– 377, DOI: 10.1016/j.phrs.2019.01.019286https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFyksLo%253D&md5=c398cbf6bc9cc75591333d1e01ae7de0The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acidsFelizardo, R. J. F.; Mizuno Watanabe, Ingrid Kazue; Dardi, Patrizia; Venturini Rossoni, Luciana; Olsen Saraiva Camara, NielsPharmacological Research (2019), 141 (), 366-377CODEN: PHMREP; ISSN:1043-6618. (Elsevier Ltd.)A review. The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been assocd. with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely assocd. diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced no. of short-chain fatty acids (SCFAs) producing bacteria is assocd. with modifications in gut environment, involving redn. of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the redn. of SCFAs plasma levels. These modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria compn. and fecal metabolite profile, inducing a pos. feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota compn. can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial compn. uncovering to improve human health maintenance and, esp., for the development of new alternative therapies.
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287Canfora, E. E.; Meex, R. C. R.; Venema, K.; Blaak, E. E. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat. Rev. Endocrinol. 2019, 15, 261– 273, DOI: 10.1038/s41574-019-0156-z287https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVyrtrzN&md5=b6bb65904cdce776542156c958c2e0ebGut microbial metabolites in obesity, NAFLD and T2DMCanfora, Emanuel E.; Meex, Ruth C. R.; Venema, Koen; Blaak, Ellen E.Nature Reviews Endocrinology (2019), 15 (5), 261-273CODEN: NREABD; ISSN:1759-5029. (Nature Research)Evidence is accumulating that the gut microbiome is involved in the etiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fiber), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fiber, the major energy source for the microbiota, is limited here. This proteolytic fermn. yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermn. could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermn. in relation to obesity and obesity-assocd. insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.
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288Tahara, Y.; Yamazaki, M.; Sukigara, H.; Motohashi, H.; Sasaki, H.; Miyakawa, H.; Haraguchi, A.; Ikeda, Y.; Fukuda, S.; Shibata, S. Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue. Sci. Rep. 2018, 8, 1395, DOI: 10.1038/s41598-018-19836-7288https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MvjsFKjuw%253D%253D&md5=6333e6b0503509819433c4f1181cae9dGut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral TissueTahara Yu; Yamazaki Mayu; Sukigara Haruna; Motohashi Hiroaki; Sasaki Hiroyuki; Miyakawa Hiroki; Haraguchi Atsushi; Ikeda Yuko; Shibata Shigenobu; Tahara Yu; Fukuda Shinji; Fukuda ShinjiScientific reports (2018), 8 (1), 1395 ISSN:.Microbiota-derived short-chain fatty acids (SCFAs) and organic acids produced by the fermentation of non-digestible fibre can communicate from the microbiome to host tissues and modulate homeostasis in mammals. The microbiome has circadian rhythmicity and helps the host circadian clock function. We investigated the effect of SCFA or fibre-containing diets on circadian clock phase adjustment in mouse peripheral tissues (liver, kidney, and submandibular gland). Initially, caecal SCFA concentrations, particularly acetate and butyrate, induced significant day-night differences at high concentrations during the active period, which were correlated with lower caecal pH. By monitoring luciferase activity correlated with the clock gene Period2 in vivo, we found that oral administration of mixed SCFA (acetate, butyrate, and propionate) and an organic acid (lactate), or single administration of each SCFA or lactate for three days, caused phase changes in the peripheral clocks with stimulation timing dependency. However, this effect was not detected in cultured fibroblasts or cultured liver slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect modulation of circadian clocks in vivo. Finally, cellobiose-containing diets facilitated SCFA production and refeeding-induced peripheral clock entrainment. SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock adjustment, suggesting prebiotics as novel therapeutic candidates for misalignment.
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289Feng, W.; Ao, H.; Peng, C. Gut Microbiota, Short-Chain Fatty Acids, and Herbal Medicines. Front. Pharmacol. 2018, 9, 1354, DOI: 10.3389/fphar.2018.01354289https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVGmt7fM&md5=bb45526d6fcc36ea07eb55386de4e4b0Gut microbiota, short-chain fatty acids, and herbal medicinesFeng, Wuwen; Ao, Hui; Peng, ChengFrontiers in Pharmacology (2018), 9 (), 1354CODEN: FPRHAU; ISSN:1663-9812. (Frontiers Media S.A.)A review. As an important source for traditional medical systems such as Ayurvedic medicine and traditional Chinesemedicine, herbalmedicines have received widespread attentions from all over the world, esp. in developing countries. Over the past decade, studies on gut microbiota have generated rich information for understanding how gut microbiota shape the functioning of our body system. In view of the importance of gutmicrobiota, the researchers engaged in studying herbal medicines have paid more and more attention to gut microbiota and gut microbiota metabolites. Among a variety of gut microbiota metabolites, short-chain fatty acids (SCFAs) have received most attention because of their important role in maintaining the hemostasis of hosts and recovery of diseases. Herbal medicines, as an important resource provider for prodn. of SCFAs, have been demonstrated to be able to modulate gut microbiota compn. and regulate SCFAs prodn. In this mini-review, we summarize current knowledge about SCFAs origination, the role of SCFAs in health and disease, the influence of herbal medicine on SCFAs prodn. and the corresponding mechanisms. At the end of this review, the strategies and suggestions for further research of SCFAs and herbal medicines are also discussed.
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290Pan, L. L.; Li, B. B.; Pan, X. H.; Sun, J. Gut microbiota in pancreatic diseases: possible new therapeutic strategies. Acta Pharmacol. Sin. 2021, 42, 1027– 1039, DOI: 10.1038/s41401-020-00532-0290https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1ersLzI&md5=f5b631fb45a432e9c11987d3ed7eef92Gut microbiota in pancreatic diseases: possible new therapeutic strategiesPan, Li-long; Li, Bin-bin; Pan, Xiao-hua; Sun, JiaActa Pharmacologica Sinica (2021), 42 (7), 1027-1039CODEN: APSCG5; ISSN:1671-4083. (Nature Portfolio)Abstr.: Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential mol. mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clin. potential to reduce the cost of pancreatic diseases.
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291Perino, A.; Demagny, H.; Velazquez-Villegas, L.; Schoonjans, K. Molecular Physiology of Bile Acid Signaling in Health, Disease, and Aging. Physiol. Rev. 2021, 101, 683– 731, DOI: 10.1152/physrev.00049.2019291https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsV2rtLfM&md5=e40a91623bb6a6e5d72940b486bf7207Molecular physiology of bile acid signaling in health, disease, and agingPerino, Alessia; Demagny, Hadrien; Velazquez-Villegas, Laura; Schoonjans, KristinaPhysiological Reviews (2021), 101 (2), 683-731CODEN: PHREA7; ISSN:1522-1210. (American Physiological Society)Over the past two decades, bile acids (BAs) have become established as important signaling mols. that enable fine-tuned inter-tissue communication from the liver, their site of prodn., over the intestine, where they are modified by the gut microbiota, to virtually any organ, where they exert their pleiotropic physiol. effects. The chem. variety of BAs, to a large extent detd. by the gut microbiome, also allows for a complex fine-tuning of adaptive responses in our body. This review provides an overview of the mechanisms by which BA receptors coordinate several aspects of physiol. and highlights new therapeutic strategies for diseases underlying pathol. BA signaling.
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292Wahlström, A.; Sayin, S. I.; Marschall, H. U.; Bäckhed, F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016, 24, 41– 50, DOI: 10.1016/j.cmet.2016.05.005292https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7hsFCksg%253D%253D&md5=4511dc3bf1227613cfc8758c24f3d1c0Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host MetabolismWahlstrom Annika; Sayin Sama I; Marschall Hanns-Ulrich; Backhed FredrikCell metabolism (2016), 24 (1), 41-50 ISSN:.The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition.
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293Poland, J. C.; Flynn, C. R. Bile Acids, Their Receptors, and the Gut Microbiota. Physiology (Bethesda) 2021, 36, 235– 245, DOI: 10.1152/physiol.00028.2020293https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c3hsVagsA%253D%253D&md5=21524b7bd10b81a547092fba07c511aaBile Acids, Their Receptors, and the Gut MicrobiotaPoland James C; Flynn C RobbPhysiology (Bethesda, Md.) (2021), 36 (4), 235-245 ISSN:.Bile acids (BAs) are a family of hydroxylated steroids secreted by the liver that aid in the breakdown and absorption of dietary fats. BAs also function as nutrient and inflammatory signaling molecules, acting through cognate receptors, to coordinate host metabolism. Commensal bacteria in the gastrointestinal tract are functional modifiers of the BA pool, affecting composition and abundance. Deconjugation of host BAs creates a molecular network that inextricably links gut microtia with their host. In this review we highlight the roles of BAs in mediating this mutualistic relationship with a focus on those events that impact host physiology and metabolism.
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294Govindarajan, K.; MacSharry, J.; Casey, P. G.; Shanahan, F.; Joyce, S. A.; Gahan, C. G. M. Unconjugated Bile Acids Influence Expression of Circadian Genes: A Potential Mechanism for Microbe-Host Crosstalk. PLoS One 2016, 11, e0167319 DOI: 10.1371/journal.pone.0167319294https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXktFaitrg%253D&md5=f9ce0ed944d15813a8e055d849bc5580Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalkGovindarajan, Kalaimathi; MacSharry, John; Casey, Patrick G.; Shanahan, Fergus; Joyce, Susan A.; Gahan, Cormac G. M.PLoS One (2016), 11 (12), e0167319/1-e0167319/13CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Disruptions to circadian rhythm in mice and humans have been assocd. with an increased risk of obesity and metabolic syndrome. The gut microbiota is known to be essential for the maintenance of circadian rhythm in the host suggesting a role for microbe-host interactions in the regulation of the peripheral circadian clock. Previous work suggested a role for gut bacterial bile salt hydrolase (BSH) activity in the regulation of host circadian gene expression. Here we demonstrate that unconjugated bile acids, known to be generated through the BSH activity of the gut microbiota, are potentially chronobiol. regulators of host circadian gene expression. We utilized a synchronised Caco-2 epithelial colorectal cell model and demonstrated that unconjugated bile acids, but not the equiv. tauro-conjugated bile salts, enhance the expression levels of genes involved in circadian rhythm. In addn. oral administration of mice with unconjugated bile acids significantly altered expression levels of circadian clock genes in the ileum and colon as well as the liver with significant changes to expression of hepatic regulators of circadian rhythm (including Dbp) and assocd. genes (Per2, Per3 and Cry2). The data demonstrate a potential mechanism for microbe-host crosstalk that significantly impacts upon host circadian gene expression.
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295McMillin, M.; DeMorrow, S. Effects of bile acids on neurological function and disease. FASEB J. 2016, 30, 3658– 3668, DOI: 10.1096/fj.201600275R295https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvV2mtbzK&md5=66ec30bab5f8afd61a577c18a5b12697Effects of bile acids on neurological function and diseaseMcmillin, Matthew; DeMorrow, SharonFASEB Journal (2016), 30 (11), 3658-3668CODEN: FAJOEC; ISSN:0892-6638. (Federation of American Societies for Experimental Biology)Bile acids are synthesized from cholesterol and are known to be involved with the emulsification and digestion of dietary lipids and fat-sol. vitamins. Outside of this role, bile acids can act as cell signaling effectors through binding and activating receptors on both the cell membrane and nucleus. Numerous reports have investigated these signaling pathways in conditions where the liver is damaged. More recently, effort has been made to investigate the role of bile acids in diseases outside of those assocd. with liver damage. This review summarizes recent findings on the influences that bile acids can exert in normal neurol. function and their contribution to diseases of the nervous system, with the intent of highlighting the role of these metabolites as potential players in neurol. disorders.
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296Roth, W.; Zadeh, K.; Vekariya, R.; Ge, Y.; Mohamadzadeh, M. Tryptophan Metabolism and Gut-Brain Homeostasis. Int. J. Mol. Sci. 2021, 22, 2973, DOI: 10.3390/ijms22062973296https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXht1OitL%252FN&md5=2b067a8c7e8ea4f3283bca2798d5f93eTryptophan metabolism and gut-brain homeostasisRoth, William; Zadeh, Kimia; Vekariya, Rushi; Ge, Yong; Mohamadzadeh, MansourInternational Journal of Molecular Sciences (2021), 22 (6), 2973CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)A review. Tryptophan is an essential amino acid crit. for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degrdation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Addnl., tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurol. and psychiatric disorders. Gut microbes influence tryptophan metab. directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurol. and psychiatric disorders where tryptophan and its metabolites play a prominent role. In we will touch upon some of these features and their involvement in health and disease.
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297Zhang, J.; Zhu, S.; Ma, N.; Johnston, L. J.; Wu, C.; Ma, X. Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammation. Med. Res. Rev. 2021, 41, 1061– 1088, DOI: 10.1002/med.21752297https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlvVCgu7g%253D&md5=8f82f6574152862aa3706b034e261b12Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammationZhang, Jie; Zhu, Shengwei; Ma, Ning; Johnston, Lee J.; Wu, Chaodong; Ma, XiMedicinal Research Reviews (2021), 41 (2), 1061-1088CODEN: MRREDD; ISSN:0198-6325. (John Wiley & Sons, Inc.)A review. In a complex, diverse intestinal environment, commensal microbiota metabolizes excessive dietary tryptophan to produce more bioactive metabolites connecting with kinds of diverse process, such as host physiol. defense, homeostasis, excessive immune activation and the progression and outcome of different diseases, such as inflammatory bowel disease, irritable bowel syndrome and others. Although commensal microbiota includes bacteria, fungi, and protozoa and all that, they often have the similar metabolites in tryptophan metab. process via same or different pathways. These metabolites can work as signal to activate the innate immunity of intestinal mucosa and induce the rapid inflammation response. They are crit. in reconstruction of lumen homeostasis as well. This review aims to seek the potential function and mechanism of microbiota-derived tryptophan metabolites as targets to regulate and shape intestinal immune function, which mainly focused on two aspects. First, analyze the character of tryptophan metab. in bacteria, fungi, and protozoa, and assess the functions of their metabolites (including indole and eight other derivs., serotonin (5-HT) and -tryptophan) on regulating the integrity of intestinal epithelium and the immunity of the intestinal mucosa. Second, focus on the mediator and pathway for their recognition, transfer and crosstalk between microbiota-derived tryptophan metabolites and intestinal mucosal immunity. Disruption of intestinal homeostasis has been described in different intestinal inflammatory diseases, available data suggest the remarkable potential of tryptophan-derived aryl hydrocarbon receptor agonists, indole derivs. on lumen equil. These metabolites as preventive and therapeutic interventions have potential to promote proinflammatory or anti-inflammatory responses of the gut.
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298Modoux, M.; Rolhion, N.; Mani, S.; Sokol, H. Tryptophan Metabolism as a Pharmacological Target. Trends Pharmacol. Sci. 2021, 42, 60– 73, DOI: 10.1016/j.tips.2020.11.006298https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVags7bF&md5=8185b6cec8cafad33abfa47edccc14d3Tryptophan Metabolism as a Pharmacological TargetModoux, Morgane; Rolhion, Nathalie; Mani, Sridhar; Sokol, HarryTrends in Pharmacological Sciences (2021), 42 (1), 60-73CODEN: TPHSDY; ISSN:0165-6147. (Elsevier Ltd.)A review. L-Tryptophan is an essential amino acid required for protein synthesis. It undergoes an extensive and complex metab. along several pathways, resulting in many bioactive mols. acting in various organs through different action mechanisms. Enzymes involved in its metab., metabolites themselves, or their receptors, represent potential therapeutic targets, which are the subject of dynamic research. Disruptions in L-tryptophan metab. are reported in several neurol., metabolic, psychiatric, and intestinal disorders, paving the way to develop drugs to target it. This review will briefly describe L-tryptophan metab. and present and discuss the most recent pharmacol. developments targeting it.
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299Roager, H. M.; Licht, T. R. Microbial tryptophan catabolites in health and disease. Nat. Commun. 2018, 9, 3294, DOI: 10.1038/s41467-018-05470-4299https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c7ptlCrtg%253D%253D&md5=7ec59a169558847e494dd14b59447737Microbial tryptophan catabolites in health and diseaseRoager Henrik M; Roager Henrik M; Licht Tine RNature communications (2018), 9 (1), 3294 ISSN:.Accumulating evidence implicates metabolites produced by gut microbes as crucial mediators of diet-induced host-microbial cross-talk. Here, we review emerging data suggesting that microbial tryptophan catabolites resulting from proteolysis are influencing host health. These metabolites are suggested to activate the immune system through binding to the aryl hydrocarbon receptor (AHR), enhance the intestinal epithelial barrier, stimulate gastrointestinal motility, as well as secretion of gut hormones, exert anti-inflammatory, anti-oxidative or toxic effects in systemic circulation, and putatively modulate gut microbial composition. Tryptophan catabolites thus affect various physiological processes and may contribute to intestinal and systemic homeostasis in health and disease.
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300Agus, A.; Planchais, J.; Sokol, H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe 2018, 23, 716– 724, DOI: 10.1016/j.chom.2018.05.003300https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFCqtrjO&md5=690e7ed63e96a101269ff4165f917902Gut Microbiota Regulation of Tryptophan Metabolism in Health and DiseaseAgus, Allison; Planchais, Julien; Sokol, HarryCell Host & Microbe (2018), 23 (6), 716-724CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)A review. The gut microbiota is a crucial actor in human physiol. Many of these effects are mediated by metabolites that are either produced by the microbes or derived from the transformation of environmental or host mols. Among the array of metabolites at the interface between these microorganisms and the host is the essential arom. amino acid tryptophan (Trp). In the gut, the three major Trp metab. pathways leading to serotonin (5-hydroxytryptamine), kynurenine (Kyn), and indole derivs. are under the direct or indirect control of the microbiota. In this review, we gather the most recent advances concerning the central role of Trp metab. in microbiota-host crosstalk in health and disease. Deciphering the complex equil. between these pathways will facilitate a better understanding of the pathogenesis of human diseases and open therapeutic opportunities.
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301Wang, Z.; Bergeron, N.; Levison, B. S.; Li, X. S.; Chiu, S.; Jia, X.; Koeth, R. A.; Li, L.; Wu, Y.; Tang, W. H. W. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur. Heart J. 2019, 40, 583– 594, DOI: 10.1093/eurheartj/ehy799301https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjsFeks74%253D&md5=63b4295582c8062536b42fbb426e6f53Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and womenWang, Zeneng; Bergeron, Nathalie; Levison, Bruce S.; Li, Xinmin S.; Chiu, Sally; Jia, Xun; Koeth, Robert A.; Li, Lin; Wu, Yuping; Tang, W. H. Wilson; Krauss, Ronald M.; Hazen, Stanley L.European Heart Journal (2019), 40 (7), 583-594CODEN: EHJODF; ISSN:1522-9645. (Oxford University Press)Aims Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore the impact of chronic dietary patterns on TMAO levels, metab. and renal excretion. Methods and results Volunteers (N = 113) were enrolled in a randomized 2-arm (high- or low-satd. fat) crossover design study. Within each arm, three 4-wk isocaloric diets (with washout period between each) were evaluated (all meals prepd. in metabolic kitchen with 25% calories from protein) to examine the effects of red meat, white meat, or non-meat protein on TMAO metab. Trimethylamine N-oxide and other trimethylamine (TMA) related metabolites were quantified at the end of each diet period. A random subset (N = 13) of subjects also participated in heavy isotope tracer studies. Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine, γ-butyrobetaine, and crotonobetaine (P < 0.05).
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302Zhang, Y.; Wang, Y.; Ke, B.; Du, J. TMAO: how gut microbiota contributes to heart failure. Transl. Res. 2021, 228, 109– 125, DOI: 10.1016/j.trsl.2020.08.007302https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVeqtLbL&md5=de42e2d7b7c56657dbcd149b1a22e064TMAO: how gut microbiota contributes to heart failureZhang, Yixin; Wang, Yuan; Ke, Bingbing; Du, JieTranslational Research (2021), 228 (), 109-125CODEN: TRRECL; ISSN:1878-1810. (Elsevier B.V.)A review. An increasing amt. of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathol. of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathol. processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gut-TMAO-HF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research.
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303Yang, S.; Li, X.; Yang, F.; Zhao, R.; Pan, X.; Liang, J.; Tian, L.; Li, X.; Liu, L.; Xing, Y. Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target. Front. Pharmacol. 2019, 10, 1360, DOI: 10.3389/fphar.2019.01360303https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhs12gsb7F&md5=bb8715d400eb6dcd9c5913c7f3e22cc3Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic TargetYang, Shengjie; Li, Xinye; Yang, Fan; Zhao, Ran; Pan, Xiandu; Liang, Jiaqi; Tian, Li; Li, Xiaoya; Liu, Longtao; Xing, Yanwei; Wu, MinFrontiers in Pharmacology (2019), 10 (), 1360CODEN: FPRHAU; ISSN:1663-9812. (Frontiers Media S.A.)Cardiovascular disease is the leading cause of death worldwide, esp. in developed countries, and atherosclerosis (AS) is the common pathol. basis of many cardiovascular diseases such as coronary heart disease. The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide, an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In this review, we discuss the TMAO-involved mechanisms of atherosclerotic CVD from the perspective of inflammation, inflammation-related immunity, cholesterol metab., and atherothrombosis. We also summarize available clin. studies on the role of TMAO in predicting prognostic outcomes, including major adverse cardiovascular events, in patients presenting with AS. Finally, since TMAO may be a novel therapeutic target for AS, several therapeutic strategies including drugs, dietary, etc. to lower TMAO levels that are currently being explored are also discussed.
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304Rudzki, L.; Stone, T. W.; Maes, M.; Misiak, B.; Samochowiec, J.; Szulc, A. Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021, 107, 110240, DOI: 10.1016/j.pnpbp.2020.110240304https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3svosFGksQ%253D%253D&md5=ae0e6a49e8f1ae5c922b388f898744fdGut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and diseaseRudzki Leszek; Stone Trevor W; Maes Michael; Misiak Blazej; Samochowiec Jerzy; Szulc AgataProgress in neuro-psychopharmacology & biological psychiatry (2021), 107 (), 110240 ISSN:.Despite the well-established roles of B-vitamins and their deficiencies in health and disease, there is growing evidence indicating a key role of those nutrients in functions of the central nervous system and in psychopathology. Clinical data indicate the substantial role of B-vitamins in various psychiatric disorders, including major depression, bipolar disorder, schizophrenia, autism, and dementia, including Alzheimer's and Parkinson's diseases. As enzymatic cofactors, B-vitamins are involved in many physiological processes such as the metabolism of glucose, fatty acids and amino acids, metabolism of tryptophan in the kynurenine pathway, homocysteine metabolism, synthesis and metabolism of various neurotransmitters and neurohormones including serotonin, dopamine, adrenaline, acetylcholine, GABA, glutamate, D-serine, glycine, histamine and melatonin. Those vitamins are highly involved in brain energetic metabolism and respiration at the cellular level. They have a broad range of anti-inflammatory, immunomodulatory, antioxidant and neuroprotective properties. Furthermore, some of those vitamins are involved in the regulation of permeability of the intestinal and blood-brain barriers. Despite the fact that a substantial amount of the above vitamins is acquired from various dietary sources, deficiencies are not uncommon, and it is estimated that micronutrient deficiencies affect about two billion people worldwide. The majority of gut-resident microbes and the broad range of bacteria available in fermented food, express genetic machinery enabling the synthesis and metabolism of B-vitamins and, consequently, intestinal microbiota and fermented food rich in probiotic bacteria are essential sources of B-vitamins for humans. All in all, there is growing evidence that intestinal bacteria-derived vitamins play a significant role in physiology and that dysregulation of the "microbiota-vitamins frontier" is related to various disorders. In this review, we will discuss the role of vitamins in mental health and explore the perspectives and potential of how gut microbiota-derived vitamins could contribute to mental health and psychiatric treatment.
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305Stacchiotti, V.; Rezzi, S.; Eggersdorfer, M.; Galli, F. Metabolic and functional interplay between gut microbiota and fat-soluble vitamins. Crit Rev. Food Sci. Nutr 2021, 61, 3211– 3232, DOI: 10.1080/10408398.2020.1793728305https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsFOiu77P&md5=7cd75a8903603411a5be6c4ee71dacabMetabolic and functional interplay between gut microbiota and fat-soluble vitaminsStacchiotti, Valentina; Rezzi, Serge; Eggersdorfer, Manfred; Galli, FrancescoCritical Reviews in Food Science and Nutrition (2021), 61 (19), 3211-3232CODEN: CRFND6; ISSN:1040-8398. (Taylor & Francis, Inc.)A review. Gut microbiota is a complex ecosystem seen as an extension of human genome. It represents a major metabolic interface of interaction with food components and xenobiotics in the gastrointestinal (GI) environment. In this context, the advent of modern bacterial genome sequencing technol. has enabled the identification of dietary nutrients as key determinants of gut microbial ecosystem able to modulate the host-microbiome symbiotic relationship and its effects on human health. This article provides a literature review on functional and mol. interactions between a specific group of lipids and essential nutrients, e.g., fat-sol. vitamins (FSVs), and the gut microbiota. A two-way relationship appears to emerge from the available literature with important effects on human metab., nutrition, GI physiol. and immune function. First, FSV directly or indirectly modify the microbial compn. involving for example immune system-mediated and/or metabolic mechanisms of bacterial growth or inhibition. Second, the gut microbiota influences at different levels the synthesis, metab. and transport of FSV including their bioactive metabolites that are either introduced with the diet or released in the gut via entero-hepatic circulation. A better understanding of these interactions, and of their impact on intestinal and metabolic homeostasis, will be pivotal to design new and more efficient strategies of disease prevention and therapy, and personalized nutrition.
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306Masri, O. A.; Chalhoub, J. M.; Sharara, A. I. Role of vitamins in gastrointestinal diseases. World J. Gastroenterol. 2015, 21, 5191– 5209, DOI: 10.3748/wjg.v21.i17.5191306https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtFaktr7J&md5=6ef31693fd6f1a30e51d88cde6e6276fRole of vitamins in gastrointestinal diseasesMasri, Omar A.; Chalhoub, Jean M.; Sharara, Ala I.World Journal of Gastroenterology (2015), 21 (17), 5191-5209CODEN: WJGAF2; ISSN:2219-2840. (Baishideng Publishing Group Inc.)A tremendous amt. of data from research was published over the past decades concerning the roles of different vitamins in various gastrointestinal diseases. For instance, most vitamins showed an inverse relationship with the risk of colorectal carcinoma as well as other malignancies like gastric and esophageal cancer in observational trials, however interventional trials failed to prove a clear beneficial preventive role. On the other hand, more solid evidence was obtained from high quality studies for a role of certain vitamins in specific entities. Examples for this include the therapeutic role of vitamin E in patients with nonalcoholic steatohepatitis, the additive role of vitamins B12 and D to the std. therapy of chronic hepatitis C virus, the role of vitamin C in reducing the risk of gallstones, the pos. outcome with vitamin B12 in patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1 in patients with inflammatory bowel disease. Other potential uses are yet to be elaborated, like those on celiac disease, pancreatic cancer, pancreatitis, cholestasis and other potential fields. Data from several ongoing interventional trials are expected to add to the current knowledge over the coming few years. Given that vitamin supplementation is psychol. accepted by patients as a natural compd. with relative safety and low cost, their use should be encouraged in the fields where pos. data are available.
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307McCarville, J. L.; Chen, G. Y.; Cuevas, V. D.; Troha, K.; Ayres, J. S. Microbiota Metabolites in Health and Disease. Annu. Rev. Immunol. 2020, 38, 147– 170, DOI: 10.1146/annurev-immunol-071219-125715307https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXotVGntrk%253D&md5=c59095f280dd378b705afa9b15380a35Microbiota Metabolites in Health and DiseaseMcCarville, Justin L.; Chen, Grischa Y.; Cuevas, Victor D.; Troha, Katia; Ayres, Janelle S.Annual Review of Immunology (2020), 38 (), 147-170CODEN: ARIMDU; ISSN:0732-0582. (Annual Reviews)A review. Metab. is one of the strongest drivers of interkingdom interactions-including those between microorganisms and their multicellular hosts. Traditionally thought to fuel energy requirements and provide building blocks for biosynthetic pathways, metab. is now appreciated for its role in providing metabolites, small-mol. intermediates generated from metabolic processes, to perform various regulatory functions to mediate symbiotic relationships between microbes and their hosts. Here, we review recent advances in our mechanistic understanding of how microbiota-derived metabolites orchestrate and support physiol. responses in the host, including immunity, inflammation, defense against infections, and metab. Understanding how microbes metabolically communicate with their hosts will provide us an opportunity to better describe how a host interacts with all microbes-beneficial, pathogenic, and commensal-and an opportunity to discover new ways to treat microbial-driven diseases.
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308Wang, Y.; Li, N.; Yang, J. J.; Zhao, D. M.; Chen, B.; Zhang, G. Q.; Chen, S.; Cao, R. F.; Yu, H.; Zhao, C. Y. Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder. Pharmacol. Res. 2020, 157, 104784, DOI: 10.1016/j.phrs.2020.104784308https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXptVChs7w%253D&md5=c107eaa07acc8541d964e2cf46379c73Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorderWang, Ying; Li, Ning; Yang, Jun-Jie; Zhao, Dong-Mei; Chen, Bin; Zhang, Guo-Qing; Chen, Shuo; Cao, Rui-Fang; Yu, Han; Zhao, Chang-Ying; Zhao, Lu; Ge, Yong-Sheng; Liu, Yi; Zhang, Le-Hai; Hu, Wei; Zhang, Lei; Gai, Zhong-TaoPharmacological Research (2020), 157 (), 104784CODEN: PHMREP; ISSN:1043-6618. (Elsevier Ltd.)The prevalence of autism spectrum disorders (ASD) is increasing, but its etiol. remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathol. and more human research is needed. This study was divided into two stages,. At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were obsd. at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant redn. in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metab. disorder (decreased homovanillic acid) were obsd. in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addn., our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in assocn. with improved ASD symptoms, including a hyper-serotonergic state and dopamine metab. disorder.
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309Morais, L. H.; Schreiber, H. L. t.; Mazmanian, S. K. The gut microbiota-brain axis in behaviour and brain disorders. Nat. Rev. Microbiol. 2021, 19, 241– 255, DOI: 10.1038/s41579-020-00460-0309https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFGqtb3O&md5=2baa4b73ccf5194f9aae45b8c6df701fThe gut microbiota-brain axis in behaviour and brain disordersMorais, Livia H.; Schreiber IV, Henry L.; Mazmanian, Sarkis K.Nature Reviews Microbiology (2021), 19 (4), 241-255CODEN: NRMACK; ISSN:1740-1526. (Nature Research)Abstr.: In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the 'gut-brain axis'. These processes may affect human health, as certain animal behaviors appear to correlate with the compn. of gut bacteria, and disruptions in microbial communities have been implicated in several neurol. disorders. Most insights about host-microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biol. systems, and possible contributions by the gut microbiota to neurol. disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health.
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310Cani, P. D.; Amar, J.; Iglesias, M. A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A. M.; Fava, F.; Tuohy, K. M.; Chabo, C. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56, 1761– 1772, DOI: 10.2337/db06-1491310https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXnvVWjurk%253D&md5=0021ad14696d8ef622651cded925b58eMetabolic endotoxemia initiates obesity and insulin resistanceCani, Patrice D.; Amar, Jacques; Iglesias, Miguel Angel; Poggi, Marjorie; Knauf, Claude; Bastelica, Delphine; Neyrinck, Audrey M.; Fava, Francesca; Tuohy, Kieran M.; Chabo, Chantal; Waget, Aurelie; Delmee, Evelyne; Cousin, Beatrice; Sulpice, Thierry; Chamontin, Bernard; Ferrieres, Jean; Tanti, Jean-Francois; Gibson, Glenn R.; Casteilla, Louis; Delzenne, Nathalie M.; Alessi, Marie Christine; Burcelin, RemyDiabetes (2007), 56 (7), 1761-1772CODEN: DIAEAZ; ISSN:0012-1797. (American Diabetes Association)Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, resp., on a nutritional basis and that a 4-wk high-fat diet chronically increased plasma LPS concn. two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-contg. microbiota in the gut. When metabolic endotoxemia was induced for 4 wk in mice through continuous s.c. infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue wt. gain were increased to a similar extent as in high-fat-fed mice. In addn., adipose tissue F4/80-pos. cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body wt. gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concn. could be a potent strategy for the control of metabolic diseases.
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311Serino, M.; Luche, E.; Gres, S.; Baylac, A.; Bergé, M.; Cenac, C.; Waget, A.; Klopp, P.; Iacovoni, J.; Klopp, C. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 2012, 61, 543– 553, DOI: 10.1136/gutjnl-2011-301012311https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmsFOis70%253D&md5=5cf617bd75501023775b64d89f1677a7Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiotaSerino, Matteo; Luche, Elodie; Gres, Sandra; Baylac, Audrey; Berge, Mathieu; Cenac, Claire; Waget, Aurelie; Klopp, Pascale; Iacovoni, Jason; Klopp, Christophe; Mariette, Jerome; Bouchez, Olivier; Lluch, Jerome; Ouarne, Francoise; Monsan, Pierre; Valet, Philippe; Roques, Christine; Amar, Jacques; Bouloumie, Anne; Theodorou, Vassilia; Burcelin, RemyGut (2012), 61 (4), 543-553CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. Methods The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an addnl. group of mice was given a glucooligosaccharide (GOS)-supplemented HFD (HFD+GOS). Results Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was assocd. with increased gut permeability linked to increased endotoxemia and to a dramatic increase in cell no. in the stroma vascular fraction from visceral white adipose tissue. Most of the physiol. characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibers. Conclusions The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.
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312Ostojic, S. M. Inadequate Production of H(2) by Gut Microbiota and Parkinson Disease. Trends Endocrinol Metab 2018, 29, 286– 288, DOI: 10.1016/j.tem.2018.02.006312https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXivVCku7Y%253D&md5=eb96ab049fcf5d094e14786a4e627731Inadequate Production of H2 by Gut Microbiota and Parkinson DiseaseOstojic, Sergej M.Trends in Endocrinology and Metabolism (2018), 29 (5), 286-288CODEN: TENME4; ISSN:1043-2760. (Elsevier Ltd.)A review. Dysbiosis of the gut flora accompanies Parkinson disease (PD), yet no specific cause-effect link has been identified so far. The gut microbiota produce mol. hydrogen (H2), a ubiquitous mol. recently recognized as a biol. active gas with antioxidant, antiapoptotic, anti-inflammatory, cytoprotective, and signaling properties. Here, we discuss an idea that an impaired prodn. of endogenous H2 by intestinal microbiota might play a role in PD pathogenesis, with supplemental H2 debated as a possible therapy for this progressive neurodegenerative disease.
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313Kalantar-Zadeh, K.; Berean, K. J.; Burgell, R. E.; Muir, J. G.; Gibson, P. R. Intestinal gases: influence on gut disorders and the role of dietary manipulations. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 733– 747, DOI: 10.1038/s41575-019-0193-z313https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhvVShurnN&md5=8897dbad5ca2972fdfb292a4ebba4ccbIntestinal gases: influence on gut disorders and the role of dietary manipulationsKalantar-Zadeh, Kourosh; Berean, Kyle J.; Burgell, Rebecca E.; Muir, Jane G.; Gibson, Peter R.Nature Reviews Gastroenterology & Hepatology (2019), 16 (12), 733-747CODEN: NRGHA9; ISSN:1759-5045. (Nature Research)A review. The inner workings of the intestines, in which the body and microbiome intersect to influence gut function and systemic health, remain elusive. Carbon dioxide, hydrogen, methane and hydrogen sulfide, as well as a variety of trace gases, are generated by the chem. interactions and microbiota within the gut. Profiling of these intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. Indeed, different tools for measuring these intestinal gases have been developed, including newly developed gas-sensing capsule technol. Gases can, according to their type, concn. and vol., induce or relieve abdominal symptoms, and might also have physiol., pathogenic and therapeutic effects. Thus, profiling and modulating intestinal gases could be powerful tools for disease prevention and/or therapy. As the interactions between the microbiota, chem. constituents and fermentative substrates of the gut are principally influenced by dietary intake, altering the diet, which, in turn, changes gas profiles, is the main therapeutic approach for gastrointestinal disorders. An improved understanding of the complex interactions within the intestines that generate gases will enhance our ability to prevent, diagnose, treat and monitor many gastrointestinal disorders.
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314Pacher, P.; Beckman, J. S.; Liaudet, L. Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 2007, 87, 315– 424, DOI: 10.1152/physrev.00029.2006314https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXitVagsr8%253D&md5=43534aa55fe52c09a2c19d04e8a652ddNitric oxide and peroxynitrite in health and diseasePacher, Pal; Beckman, Joseph S.; Liaudet, LucasPhysiological Reviews (2007), 87 (1), 315-424CODEN: PHREA7; ISSN:0031-9333. (American Physiological Society)A review. The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biol. and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every crit. cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacol. strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.
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315Singh, S. B.; Lin, H. C. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms 2015, 3, 866– 889, DOI: 10.3390/microorganisms3040866315https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXltFCht7s%253D&md5=4a8fd11434a2cff9c586ba62d5e68c59Hydrogen sulfide in physiology and diseases of the digestive tractSingh, Sudha B.; Lin, Henry C.Microorganisms (2015), 3 (4), 866-889CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Hydrogen sulfide (H2S) is a Janus-faced mol. On one hand, several toxic functions have been attributed to H2S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H2S delivery based clin. therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H2S has been found to have pleiotropic effects on physiol. and health. H2S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addn. to H2S prodn. by mammalian cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), H2S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate redn. (DSR) pathway. In the gut, H2S regulates functions such as inflammation, ischemia/reperfusion injury and motility. H2S derived from gut microbes has been found to be assocd. with gastrointestinal disorders such as ulcerative colitis, Crohn's disease and irritable bowel syndrome. This underscores the importance of gut microbes and their prodn. of H2S on host physiol. and pathophysiol.
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316Sen, N. Functional and Molecular Insights of Hydrogen Sulfide Signaling and Protein Sulfhydration. J. Mol. Biol. 2017, 429, 543– 561, DOI: 10.1016/j.jmb.2016.12.015316https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitFGhsbvI&md5=4845c8ac79246a01df007496188e982dFunctional and Molecular Insights of Hydrogen Sulfide Signaling and Protein SulfhydrationSen, NilkanthaJournal of Molecular Biology (2017), 429 (4), 543-561CODEN: JMOBAK; ISSN:0022-2836. (Elsevier Ltd.)A review. Hydrogen sulfide (H2S), a novel gasotransmitter, is endogenously synthesized by multiple enzymes that are differentially expressed in the peripheral tissues and central nervous systems. H2S regulates a wide range of physiol. processes, namely cardiovascular, neuronal, immune, respiratory, gastrointestinal, liver, and endocrine systems, by influencing cellular signaling pathways and sulfhydration of target proteins. This review focuses on the recent progress made in H2S signaling that affects mechanistic and functional aspects of several biol. processes such as autophagy, inflammation, proliferation and differentiation of stem cell, cell survival/death, and cellular metab. under both physiol. and pathol. conditions. Moreover, we highlighted the cross-talk between nitric oxide and H2S in several biol. contexts.
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317Skonieczna-Żydecka, K.; Marlicz, W.; Misera, A.; Koulaouzidis, A.; Łoniewski, I. Microbiome─The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health. Journal of Clinical Medicine 2018, 7, 521, DOI: 10.3390/jcm7120521There is no corresponding record for this reference.
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318Schmulson, M. J.; Drossman, D. A. What Is New in Rome IV. J. Neurogastroenterol. Motil. 2017, 23, 151– 163, DOI: 10.5056/jnm16214318https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czkt1Kmug%253D%253D&md5=ef944cf8294c397a77f10dbb49e81a12What Is New in Rome IVSchmulson Max J; Drossman Douglas A; Drossman Douglas AJournal of neurogastroenterology and motility (2017), 23 (2), 151-163 ISSN:2093-0879.Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the Rome criteria; the criteria may change over time as new scientific data emerge. The Rome IV was released in May 2016. The aim is to review the main changes in Rome IV. FGIDs are now called disorders of gut-brain interaction (DGBI). Rome IV has a multicultural rather than a Western-culture focus. There are new chapters including multicultural, age-gender-women's health, intestinal microenvironment, biopsychosocial, and centrally mediated disorders. New disorders have been included although not truly FGIDs, but fit the new definition of DGBI including opioid-induced gastrointestinal hyperalgesia , opioid-induced constipation , and cannabinoid hyperemesis . Also, new FGIDs based on available evidence including reflux hypersensitivity and centrally mediated abdominal pain syndrome . Using a normative survey to determine the frequency of normal bowel symptoms in the general population changes in the time frame for diagnosis were introduced. For irritable bowel syndrome (IBS) only pain is required and discomfort was eliminated because it is non-specific, having different meanings in different languages. Pain is now related to bowel movements rather than just improving with bowel movements (ie, can get worse with bowel movement). Functional bowel disorders (functional diarrhea , functional constipation , IBS with predominant diarrhea [IBS-D], IBS with predominant constipation [IBS-C ], and IBS with mixed bowel habits ) are considered to be on a continuum rather than as independent entities. Clinical applications such as diagnostic algorithms and the Multidimensional Clinical Profile have been updated. The new Rome IV iteration is evidence-based, multicultural oriented and with clinical applications. As new evidence become available, future updates are expected.
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319Stasi, C.; Nisita, C.; Cortopassi, S.; Corretti, G.; Gambaccini, D.; De Bortoli, N.; Fani, B.; Simonetti, N.; Ricchiuti, A.; Dell’Osso, L. Subthreshold Psychiatric Psychopathology in Functional Gastrointestinal Disorders: Can It Be the Bridge between Gastroenterology and Psychiatry?. Gastroenterol. Res. Pract. 2017, 2017, 1953435, DOI: 10.1155/2017/1953435319https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M3oslGisA%253D%253D&md5=ab67afe646cf40eb0c1e04990e44d0adSubthreshold Psychiatric Psychopathology in Functional Gastrointestinal Disorders: Can It Be the Bridge between Gastroenterology and Psychiatry?Stasi Cristina; Nisita Cristiana; Cortopassi Sonia; Dell'Osso Liliana; Corretti Giorgio; Gambaccini Dario; De Bortoli Nicola; Fani Bernardo; Simonetti Natalia; Ricchiuti Angelo; Marchi Santino; Bellini MassimoGastroenterology research and practice (2017), 2017 (), 1953435 ISSN:1687-6121.BACKGROUND AND AIMS: Functional gastrointestinal disorders (FGDs) are multifactorial disorders of the gut-brain interaction. This study investigated the prevalence of Axis I and spectrum disorders in patients with FGD and established the link between FGDs and psychopathological dimensions. METHODS: A total of 135 consecutive patients with FGD were enrolled. The symptoms' severity was evaluated using questionnaires, while the psychiatric evaluation by clinical interviews established the presence/absence of mental (Diagnostic and Statistical Manual-4th edition, Axis I Diagnosis) or spectrum disorders. RESULTS: Of the 135 patients, 42 (32.3%) had functional dyspepsia, 52 (40.0%) had irritable bowel syndrome, 21 (16.2%) had functional bloating, and 20 (15.4%) had functional constipation. At least one psychiatric disorder was present in 46.9% of the patients, while a suprathreshold panic spectrum was present in 26.2%. Functional constipation was associated with depressive disorders (p < 0.05), while functional dyspepsia was related to the current major depressive episode (p < 0.05). Obsessive-compulsive spectrum was correlated with the presence of functional constipation and irritable bowel syndrome (p < 0.05). CONCLUSION: The high prevalence of subthreshold psychiatric symptomatology in patients with FGD, which is likely to influence the expression of gastrointestinal symptoms, suggested the usefulness of psychological evaluation in patients with FGDs.
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320Cryan, J. F.; O’Riordan, K. J.; Cowan, C. S. M.; Sandhu, K. V.; Bastiaanssen, T. F. S.; Boehme, M.; Codagnone, M. G.; Cussotto, S.; Fulling, C.; Golubeva, A. V. The Microbiota-Gut-Brain Axis. Physiol. Rev. 2019, 99, 1877– 2013, DOI: 10.1152/physrev.00018.2018320https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitFWjsLs%253D&md5=efad6ac39777a0569fa724115a775361The microbiota-gut-brain axisCryan, John F.; O'Riordan, Kenneth J.; Cowan, Caitlin S. M.; Sandhu, Kiran V.; Bastiaanssen, Thomaz F. S.; Boehme, Marcus; Codagnone, Martin G.; Cussotto, Sofia; Fulling, Christine; Golubeva, Anna V.; Guzzetta, Katherine E.; Jaggar, Minal; Long-Smith, Caitriona M.; Lyte, Joshua M.; Martin, Jason A.; Molinero-Perez, Alicia; Moloney, Gerard; Morelli, Emanuela; Morillas, Enrique; O'Connor, Rory; Cruz-Pereira, Joana S.; Peterson, Veronica L.; Rea, Kieran; Ritz, Nathaniel L.; Sherwin, Eoin; Spichak, Simon; Teichman, Emily M.; van de Wouw, Marcel; Ventura-Silva, Ana Paula; Wallace-Fitzsimons, Shauna E.; Hyland, Niall; Clarke, Gerard; Dinan, Timothy G.Physiological Reviews (2019), 99 (4), 1877-2013CODEN: PHREA7; ISSN:1522-1210. (American Physiological Society)A review. The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biol. and physiol. basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metab., the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota compn. in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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321Gralnek, I. M.; Hays, R. D.; Kilbourne, A.; Naliboff, B.; Mayer, E. A. The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology 2000, 119, 654– 660, DOI: 10.1053/gast.2000.16484321https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3cvnt1amuw%253D%253D&md5=61ae873d02ae9f3dc2ea36f59b8b0b4bThe impact of irritable bowel syndrome on health-related quality of lifeGralnek I M; Hays R D; Kilbourne A; Naliboff B; Mayer E AGastroenterology (2000), 119 (3), 654-60 ISSN:0016-5085.BACKGROUND & AIMS: Few data are available to evaluate health-related quality of life (HRQOL) of people with irritable bowel syndrome (IBS). We evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the U.S. general population and for people with selected chronic diseases. METHODS: Using the SF-36 Health Survey, we compared the HRQOL of IBS patients (n = 877) with previously reported SF-36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end-stage renal disease (ESRD). RESULTS: On all 8 SF-36 scales, IBS patients had significantly worse HRQOL than the U.S. general population (P < 0. 001). Compared with GERD patients, IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF-36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF-36 scale scores than patients with depression (P < 0.001). CONCLUSIONS: IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy/fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. These data offer further insight into the impact of IBS on patient functional status and well-being.
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322O’Keeffe, M.; Lomer, M. C. Who should deliver the low FODMAP diet and what educational methods are optimal: a review. J. Gastroenterol. Hepatol. 2017, 32, 23– 26, DOI: 10.1111/jgh.13690322https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czhtlamug%253D%253D&md5=b20c62bcfe40e3459a5f44a9f3823f2fWho should deliver the low FODMAP diet and what educational methods are optimal: a reviewO'Keeffe Majella; Lomer Miranda Ce; Lomer Miranda CeJournal of gastroenterology and hepatology (2017), 32 Suppl 1 (), 23-26 ISSN:.Dietary management is being hailed as an effective strategy for the management of irritable bowel syndrome. Specifically, a diet low in fermentable carbohydrates (FODMAPs) has demonstrated efficacy in approximately 70% of patients. As evidence in support of the low FODMAP diet continues to emerge, there is increasing debate regarding implementation of the diet particularly concerning who should educate patients and how to educate them. Registered dieticians have largely pioneered the evidence that supports the effectiveness of the low FODMAP diet in irritable bowel syndrome, and the diet is recognized as a dietician-led therapy. However, there is an increasing trend for non-dietician-led implementation of the diet despite an absence of evidence on both the clinical or cost-effectiveness of such. Additionally, there is a growing requirement for dietetic services to increase capacity in response to increasing referrals, and consequently, there is a need to investigate innovative ways to educate patients whilst maintaining dietician-led intervention. Herein, we review the evidence for delivery of the low FODMAP diet and discuss potentially effective methods for service delivery.
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323Koloski, N. A.; Jones, M.; Talley, N. J. Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study. Alimentary pharmacology & therapeutics 2016, 44, 592– 600, DOI: 10.1111/apt.13738There is no corresponding record for this reference.
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324Eijsbouts, C.; Zheng, T.; Kennedy, N. A.; Bonfiglio, F.; Anderson, C. A.; Moutsianas, L.; Holliday, J.; Shi, J.; Shringarpure, S.; Agee, M. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat. Genet. 2021, 53, 1543– 1552, DOI: 10.1038/s41588-021-00950-8324https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVehtb7F&md5=84ea904f4564f6c663d42d80481f2018Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disordersEijsbouts, Chris; Zheng, Tenghao; Kennedy, Nicholas A.; Bonfiglio, Ferdinando; Anderson, Carl A.; Moutsianas, Loukas; Holliday, Joanne; Shi, Jingchunzi; Shringarpure, Suyash; Voda, Alexandru-Ioan; Farrugia, Gianrico; Franke, Andre; Hubenthal, Matthias; Abecasis, Goncalo; Zawistowski, Matthew; Skogholt, Anne Heidi; Ness-Jensen, Eivind; Hveem, Kristian; Esko, Tonu; Teder-Laving, Maris; Zhernakova, Alexandra; Camilleri, Michael; Boeckxstaens, Guy; Whorwell, Peter J.; Spiller, Robin; McVean, Gil; D'Amato, Mauro; Jostins, Luke; Parkes, MilesNature Genetics (2021), 53 (11), 1543-1552CODEN: NGENEC; ISSN:1061-4036. (Nature Portfolio)Irritable bowel syndrome (IBS) results from disordered brain-gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiol. mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide assocn. study with 53,400 cases and 433,201 controls and replicated significant assocns. in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are assocd. with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Addnl. analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain-gut interactions underlying IBS.
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325Schwarz, E.; Maukonen, J.; Hyytiäinen, T.; Kieseppä, T.; Orešič, M.; Sabunciyan, S.; Mantere, O.; Saarela, M.; Yolken, R.; Suvisaari, J. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr. Res. 2018, 192, 398– 403, DOI: 10.1016/j.schres.2017.04.017325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1crhtV2itw%253D%253D&md5=3768583481e3c898421edc538da930d1Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment responseSchwarz Emanuel; Maukonen Johanna; Hyytiainen Tiina; Saarela Maria; Kieseppa Tuula; Oresic Matej; Sabunciyan Sarven; Yolken Robert; Mantere Outi; Suvisaari JaanaSchizophrenia research (2018), 192 (), 398-403 ISSN:.The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission.
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326Castro-Nallar, E.; Bendall, M. L.; Pérez-Losada, M.; Sabuncyan, S.; Severance, E. G.; Dickerson, F. B.; Schroeder, J. R.; Yolken, R. H.; Crandall, K. A. Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls. PeerJ. 2015, 3, e1140, DOI: 10.7717/peerj.1140There is no corresponding record for this reference.
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327Belkaid, Y.; Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 2014, 157, 121– 141, DOI: 10.1016/j.cell.2014.03.011327https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtVCqsL8%253D&md5=8a9f60a467ebbefb7dba7fde7e46f423Role of the Microbiota in Immunity and InflammationBelkaid, Yasmine; Hand, Timothy W.Cell (Cambridge, MA, United States) (2014), 157 (1), 121-141CODEN: CELLB5; ISSN:0092-8674. (Cell Press)A review. The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relation of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where the authors' symbiotic relation with the microbiota has been the most affected.
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328Anderson, G.; Maes, M. Bipolar disorder: role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolites. Curr. Psychiatry Rep 2015, 17, 8, DOI: 10.1007/s11920-014-0541-1328https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MvpslSjtg%253D%253D&md5=2a5eee380a11b5e55ca19099ab9cdb93Bipolar disorder: role of immune-inflammatory cytokines, oxidative and nitrosative stress and tryptophan catabolitesAnderson George; Maes MichaelCurrent psychiatry reports (2015), 17 (2), 8 ISSN:.Bipolar disorder (BD) is a complex disorder with a range of presentations. BD is defined by the presentation of symptoms of mania or depression, with classification dependent on patient/family reports and behavioural observations. Recent work has investigated the biological underpinnings of BD, highlighting the role played by increased immune-inflammatory activity, which is readily indicated by changes in pro-inflammatory cytokines or signalling, both centrally and systemically, e.g. increased interleukin-6 trans-signalling. Here, we review the recent data on immune-inflammatory pathways and cytokine changes in BD. Such changes are intimately linked to changes in oxidative and nitrosative stress (O&NS) and neuroregulatory tryptophan catabolites (TRYCATs), both centrally and peripherally. TRYCATs take tryptophan away from serotonin, N-acetylserotonin and melatonin synthesis, driving it down the TRYCAT pathway, predominantly as a result of the pro-inflammatory cytokine induction of indoleamine 2,3-dioxygenase. This has led to an emerging biological perspective on the aetiology, course and treatment of BD. Such data also better integrates the numerous comorbidities associated with BD, including addiction, cardiovascular disorders and increased reporting of pain. Immune-inflammatory, O&NS and TRYCAT pathways are also likely to be relevant biological underpinnings to the significant decrease in life expectancy in BD.
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329Clarke, G.; Fitzgerald, P.; Cryan, J. F.; Cassidy, E. M.; Quigley, E. M.; Dinan, T. G. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. BMC Gastroenterol. 2009, 9, 6, DOI: 10.1186/1471-230X-9-6329https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M7mvVyktA%253D%253D&md5=e1e82fee8d56c114872bfc68605d15c2Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohortClarke Gerard; Fitzgerald Peter; Cryan John F; Cassidy Eugene M; Quigley Eamonn M; Dinan Timothy GBMC gastroenterology (2009), 9 (), 6 ISSN:.BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that affects 10-15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26). METHODS: Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay. RESULTS: Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio. CONCLUSION: These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.
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330Clarke, G.; McKernan, D.; Gaszner, G.; Quigley, E.; Cryan, J.; Dinan, T. A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome. Front. Pharmacol. 2012, 3, 90, DOI: 10.3389/fphar.2012.00090330https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmsVKqsbs%253D&md5=a8bf82d079221b6140978215a07b42a8A distinct profile of tryptophan metabolism along the kynurenine pathway downstream of toll-like receptor activation in irritable bowel syndromeClarke, Gerard; McKernan, Declan P.; Gaszner, Gabor; Quigley, Eamonn M.; Cryan, John F.; Dinan, Timothy G.Frontiers in Gastrointestinal Pharmacology (2012), 3 (May), 90CODEN: FGPRAL ISSN:. (Frontiers Media S.A.)Irritable bowel syndrome (IBS), a disorder of the brain-gut axis, is characterised by the absence of reliable biol. markers. Tryptophan is an essential amino acid that serves as a precursor to serotonin but which can alternatively be metabolised along the kynurenine pathway leading to the prodn. of other neuroactive agents. We previously reported an increased degrdn. of tryptophan along this immunoresponsive pathway in IBS. Recently, altered cytokine prodn. following activation of specific members of the toll-like receptor (TLR) family (TLR1-9) has also been demonstrated in IBS. However, the relationship between TLR activation and kynurenine pathway activity in IBS is unknown. In this study, we investigated whether activation of specific TLRs elicits exaggerated kynurenine prodn. in IBS patients compared to controls. Whole blood from IBS patients and healthy controls was cultured with a panel of nine different TLR agonists for 24 h. Cell culture supernatants were then analyzed for both tryptophan and kynurenine concns., as were plasma samples from both cohorts. IBS subjects had an elevated plasma kynurenine:tryptophan ratio compared to healthy controls. Furthermore, we demonstrated a differential downstream profile of kynurenine prodn. subsequent to TLR activation in IBS patients compared to healthy controls. This profile included alterations at TLR1/2, TLR2, TLR3, TLR5, TLR7, and TLR8. Our data expands on our previous understanding of altered tryptophan metab. in IBS and suggests that measurement of tryptophan metabolites downstream of TLR activation may ultimately find utility as components of a biomarker panel to aid gastroenterologists in the diagnosis of IBS. Furthermore, these studies implicate the modulation of TLRs as means through which aberrant tryptophan metab. along the kynurenine pathway can be controlled, a novel potential therapeutic strategy in this and other disorders.
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331Liang, X.; FitzGerald, G. A. Timing the Microbes: The Circadian Rhythm of the Gut Microbiome. J. Biol. Rhythms 2017, 32, 505– 515, DOI: 10.1177/0748730417729066331https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXislSrsLo%253D&md5=58f6fe2c84152d919b7b75b41bd2b34eTiming the microbes: the circadian rhythm of the gut microbiomeLiang, Xue; FitzGeraldt, Garret A.Journal of Biological Rhythms (2017), 32 (6), 505-515CODEN: JBRHEE; ISSN:0748-7304. (Sage Publications)A review. The mammalian circadian clock system, which includes the master clock and peripheral clocks, times different biol. processes in reaction to external cues, such as the light-dark cycle. However, the chronobiol. of pro- karyotic cells is less well understood, except for in cyanobacteria. The recent blooming of gut microbiome research has revealed a crit. role for the trillions of microbes residing in the vertebrate gut in detg. both health and dis- ease in the host. The question of whether the gut microbiome exhibits circadian oscillation and how it synchronizes with the host circadian clock has attracted considerable interest. In this review, we discuss the time-of-day-dependent compositional and functional structure within the gut microbial community, how it is regulated by the host, and how it reciprocally influences the host cir- cadian dock.
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332Enck, P.; Aziz, Q.; Barbara, G.; Farmer, A. D.; Fukudo, S.; Mayer, E. A.; Niesler, B.; Quigley, E. M.; Rajilić-Stojanović, M.; Schemann, M. Irritable bowel syndrome. Nat. Rev. Dis Primers 2016, 2, 16014, DOI: 10.1038/nrdp.2016.14332https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28botVWqtg%253D%253D&md5=177e4e06ce4142c039bfd8937b08683fIrritable bowel syndromeEnck Paul; Schwille-Kiuntke Juliane; Zipfel Stephan; Aziz Qasim; Farmer Adam D; Barbara Giovanni; Fukudo Shin; Mayer Emeran A; Niesler Beate; Quigley Eamonn M M; Rajilic-Stojanovic Mirjana; Schemann Michael; Simren Magnus; Spiller Robin CNature reviews. Disease primers (2016), 2 (), 16014 ISSN:.Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain-gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.
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333Dalile, B.; Vervliet, B.; Bergonzelli, G.; Verbeke, K.; Van Oudenhove, L. Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trial. Neuropsychopharmacology 2020, 45, 2257– 2266, DOI: 10.1038/s41386-020-0732-x333https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFKgtLzM&md5=d8a5d4b71e49c7a313eea32e4dfb6bd0Colon-delivered short-chain fatty acids attenuate the cortisol response to psychosocial stress in healthy men: a randomized, placebo-controlled trialDalile, Boushra; Vervliet, Bram; Bergonzelli, Gabriela; Verbeke, Kristin; Van Oudenhove, LukasNeuropsychopharmacology (2020), 45 (13), 2257-2266CODEN: NEROEW; ISSN:0893-133X. (Nature Research)Short-chain fatty acids (SCFAs) are products of microbial fermn. of dietary fiber in the colon and may mediate microbiota-gut-brain communication. However, their role in modulating psychobiol. processes that underlie the development of stress- and anxiety-related disorders is not mechanistically studied in humans. In this triple-blind, randomized, placebo-controlled intervention trial, we examine in a parallel group design the effects of 1-wk colonic SCFA-mixt. delivery in doses equiv. to fermn. of 10 g or 20 g of arabinoxylan oligosaccharides on responses to psychosocial stress and fear tasks in 66 healthy men. We demonstrate that low and high doses of SCFAs significantly attenuate the cortisol response to psychosocial stress compared to placebo. Both doses of SCFAs increase serum SCFA levels and this increase in circulating SCFAs co-varies significantly with the attenuation of the cortisol response to psychosocial stress. Colonic SCFA delivery does not modulate fecal SCFA concns., serum brain-derived neurotrophic factor, cortisol awakening response, fear learning and extinction, or subjective mood ratings. These results demonstrate that colon-delivered SCFAs modulate hypothalamic-pituitary-adrenal axis reactivity to psychosocial stress, thereby supporting their hypothesized role in microbiota-gut-brain communication.
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334Bercik, P.; Park, A. J.; Sinclair, D.; Khoshdel, A.; Lu, J.; Huang, X.; Deng, Y.; Blennerhassett, P. A.; Fahnestock, M.; Moine, D. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol. Motil. 2011, 23, 1132– 1139, DOI: 10.1111/j.1365-2982.2011.01796.x334https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xns1Kmuw%253D%253D&md5=9b3305bf4a6c9e6627db3e1dafdba5d3The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communicationBercik, P.; Park, A. J.; Sinclair, D.; Khoshdel, A.; Lu, I.; Huang, X.; Deng, Y.; Blennerhassett, P. A.; Fahnestock, M.; Moine, D.; Berger, B.; Huizinga, J. D.; Kunze, W.; McLean, P. G.; Bergonzelli, G. E.; Collins, S. M.; Verdu, E. F.Neurogastroenterology & Motility (2011), 23 (12), 1132-1139CODEN: NMOTEK; ISSN:1350-1925. (Wiley-Blackwell)The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chem. colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-wk cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histol. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was assocd. with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histol. scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. & Inferences In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or prodn. of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.
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335Mishima, Y.; Ishihara, S. Molecular Mechanisms of Microbiota-Mediated Pathology in Irritable Bowel Syndrome. Int. J. Mol. Sci. 2020, 21, 8664, DOI: 10.3390/ijms21228664335https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFyhtb3L&md5=0b6b935b69b2563c790e931794404bd4Molecular mechanisms of microbiota-mediated pathology in irritable bowel syndromeMishima, Yoshiyuki; Ishihara, ShunjiInternational Journal of Molecular Sciences (2020), 21 (22), 8664CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)A review. Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders, and accumulating evidence gained in both preclin. and clin. studies indicate the involvement of enteric microbiota in its pathogenesis. Gut resident microbiota appear to influence brain activity through the enteric nervous system, while their compn. and function are affected by the central nervous system. Based on these results, the term "brain-gut-microbiome" has been proposed and enteric microbiota have become a potential therapeutic target in IBS cases. However, details regarding the microbe-related pathophysiol. of IBS remain elusive. This review summarizes the existing knowledge of mol. mechanisms in the pathogenesis of IBS as well as recent progress related to microbiome-derived neurotransmitters, compds., metabolites, neuroendocrine factors, and enzymes.
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336Leeming, E. R.; Johnson, A. J.; Spector, T. D.; Le Roy, C. I. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients 2019, 11, 2862, DOI: 10.3390/nu11122862There is no corresponding record for this reference.
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337Hillestad, E. M. R.; van der Meeren, A.; Nagaraja, B. H.; Bjo̷rsvik, B. R.; Haleem, N.; Benitez-Paez, A.; Sanz, Y.; Hausken, T.; Lied, G. A.; Lundervold, A. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J. Gastroenterol. 2022, 28, 412– 431, DOI: 10.3748/wjg.v28.i4.412337https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XlvFalsL8%253D&md5=1035ffb12c3a336ddf4b65e4a1c0e462Gut bless you: the microbiota-gut-brain axis in irritable bowel syndromeHillestad, Eline Margrete Randulff; van der Meeren, Aina; Nagaraja, Bharat Halandur; Bjoersvik, Ben Rene; Haleem, Noman; Benitez-Paez, Alfonso; Sanz, Yolanda; Hausken, Trygve; Lied, Gulen Arslan; Lundervold, Arvid; Berentsen, BirgitteWorld Journal of Gastroenterology (2022), 28 (4), 412-431CODEN: WJGAF2; ISSN:2219-2840. (Baishideng Publishing Group Inc.)A review. Irritable bowel syndrome (IBS) is a common clin. label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiol. of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiol. mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiol., or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing. In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clin. microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data anal. in IBS.
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338Hugerth, L. W.; Andreasson, A.; Talley, N. J.; Forsberg, A. M.; Kjellström, L.; Schmidt, P. T.; Agreus, L.; Engstrand, L. No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population. Gut 2020, 69, 1076– 1084, DOI: 10.1136/gutjnl-2019-318717338https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mnmslymtg%253D%253D&md5=55d809f6c060f0fa2ddfb314d2fed1bcNo distinct microbiome signature of irritable bowel syndrome found in a Swedish random populationHugerth Luisa W; Engstrand Lars; Andreasson Anna; Andreasson Anna; Forsberg Anna M; Schmidt Peter Thelin; Andreasson Anna; Talley Nicholas J; Kjellstrom Lars; Agreus Lars; Engstrand LarsGut (2020), 69 (6), 1076-1084 ISSN:.OBJECTIVE: The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings. DESIGN: The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases). RESULTS: While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R2=0.255, p<3E-11) as was diversity (R2=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals. CONCLUSIONS: No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.
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339Sundin, J.; Aziz, I.; Nordlander, S.; Polster, A.; Hu, Y. O. O.; Hugerth, L. W.; Pennhag, A. A. L.; Engstrand, L.; Törnblom, H.; Simrén, M. Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci. Rep. 2020, 10, 593, DOI: 10.1038/s41598-020-57468-y339https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXjsVSit7w%253D&md5=fc60c1f852982038171c0216d22c5db3Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel SyndromeSundin, Johanna; Aziz, Imran; Nordlander, Sofia; Polster, Annikka; Hu, Yue O. O.; Hugerth, Luisa W.; Pennhag, Alexandra A. L.; Engstrand, Lars; Toernblom, Hans; Simren, Magnus; Oehman, LenaScientific Reports (2020), 10 (1), 593CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: Altered bacterial compn. and small intestinal bacterial overgrowth (SIBO) may be assocd. with irritable bowel syndrome (IBS). This study aimed to det. the fecal and mucosa-assocd. bacterial compn. along the gastrointestinal (GI) tract and to assess SIBO in IBS. Bacterial compn. of feces, and mucosa of the duodenum and sigmoid colon was detd. by 16S rRNA-amplicon-sequencing. SIBO was evaluated by bacterial culture of duodenal aspirate, glucose and lactulose breath tests. Mucosal antibacterial gene expression was assessed by PCR Array. The bacterial profiles of feces and the mucosa of sigmoid colon, but not duodenum, differed between IBS patients (n = 17) and HS (n = 20). The IBS specific bacterial profiles were linked to the colonic antibacterial gene expression. Fecal bacterial profile differed between IBS subtypes, while the mucosa-assocd. bacterial profile was assocd. with IBS symptom severity and breath tests results at baseline (H2 and/or CH4 ≥ 15 ppm). The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial compn. of the sigmoid colon of IBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-assocd. bacterial compn., there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS.
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340Mayer, E. A.; Labus, J.; Aziz, Q.; Tracey, I.; Kilpatrick, L.; Elsenbruch, S.; Schweinhardt, P.; Van Oudenhove, L.; Borsook, D. Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report. Gut 2019, 68, 1701– 1715, DOI: 10.1136/gutjnl-2019-318308340https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXisVCnu73M&md5=79fed8428d6c74a501436d1f274842daRole of brain imaging in disorders of brain-gut interaction: a Rome Working Team ReportMayer, Emeran A.; Labus, Jennifer; Aziz, Qasim; Tracey, Irene; Kilpatrick, Lisa; Elsenbruch, Sigrid; Schweinhardt, Petra; Van Oudenhove, Lukas; Borsook, DavidGut (2019), 68 (9), 1701-1715CODEN: GUTTAK; ISSN:0017-5749. (BMJ)A review. Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clin. symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urol. pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclin. vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
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341Seminowicz, D. A.; Labus, J. S.; Bueller, J. A.; Tillisch, K.; Naliboff, B. D.; Bushnell, M. C.; Mayer, E. A. Regional gray matter density changes in brains of patients with irritable bowel syndrome. Gastroenterology 2010, 139, 48– 57.e42, DOI: 10.1053/j.gastro.2010.03.049341https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cnms1yrsQ%253D%253D&md5=fa5d68d8fe3e8c5d06705f7de1162628Regional gray matter density changes in brains of patients with irritable bowel syndromeSeminowicz David A; Labus Jennifer S; Bueller Joshua A; Tillisch Kirsten; Naliboff Bruce D; Bushnell M Catherine; Mayer Emeran AGastroenterology (2010), 139 (1), 48-57.e2 ISSN:.BACKGROUND & AIMS: Several studies have examined structural brain changes associated with chronic pain syndromes, including irritable bowel syndrome (IBS), but study sample sizes have been small and heterogeneous. METHODS: We used magnetic resonance imaging-based techniques, voxel-based morphometry, and cortical thickness analysis to examine brain anatomical differences in a relatively large, tightly screened sample of IBS patients (n = 55); we compared data with that from healthy persons (controls; n = 48). RESULTS: IBS was associated with decreased gray matter density (GMD) in widespread areas of the brain, including medial prefrontal and ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum, and thalamus. Compared with controls, we observed increased GMD in patients with IBS in the pregenual anterior cingulate cortex and the orbitofrontal cortex, as well as trends in the posterior insula/secondary somatosensory cortex, (para)hippocampus, and left dorsolateral prefrontal cortex. In accounting for anxiety and depression, we found that several of the regions involved in affective processing no longer differed between patients with IBS and controls, whereas the differences in prefrontal and posterior parietal cortices remained. The areas of decreased GMD associated with IBS were largely consistent across clinical subgroups, based on predominant bowel habit and pain predominance of symptoms. No overall or regional differences were observed in cortical thickness between patients with IBS and controls. CONCLUSIONS: Changes in density of gray matter among regions involved in cognitive/evaluative functions are specifically observed in patients with IBS, whereas changes in other areas of the brain can be explained by levels of anxiety and depression.
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342Kano, M.; Grinsvall, C.; Ran, Q.; Dupont, P.; Morishita, J.; Muratsubaki, T.; Mugikura, S.; Ly, H. G.; Törnblom, H.; Ljungberg, M. Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysis. Sci. Rep. 2020, 10, 11015, DOI: 10.1038/s41598-020-67048-9342https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlClsb3P&md5=b7f4ea6496a4628d56c6644c1b7a49a7Resting state functional connectivity of the pain matrix and default mode network in irritable bowel syndrome: a graph theoretical analysisKano, Michiko; Grinsvall, Cecilia; Ran, Qian; Dupont, Patrick; Morishita, Joe; Muratsubaki, Tomohiko; Mugikura, Shunji; Ly, Huynh Giao; Tornblom, Hans; Ljungberg, Maria; Takase, Kei; Simren, Magnus; Van Oudenhove, Lukas; Fukudo, ShinScientific Reports (2020), 10 (1), 11015CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: Irritable bowel syndrome (IBS) is a functional disorder of brain-gut interactions. Differential brain responses to rectal distention between IBS and healthy controls (HCs) have been demonstrated, particularly in the pain matrix and the default mode network. This study aims to compare resting-state functional properties of these networks between IBS patients and HCs using graph anal. in two independent cohorts. We used a weighted graph anal. of the adjacency matrix based on partial correlations between time series in the different regions in each subject to det. subject specific graph measures. These graph measures were normalized by values obtained in equiv. random networks. We did not find any significant differences between IBS patients and controls in global normalized graph measures, hubs, or modularity structure of the pain matrix and the DMN in any of our two independent cohorts. Furthermore, we did not find consistent assocns. between these global network measures and IBS symptom severity or GI-specific anxiety but we found a significant difference in the relationship between measures of psychol. distress (anxiety and/or depressive symptoms) and normalized characteristic path length. The responses of these networks to visceral stimulation rather than their organization at rest may be primarily disturbed in IBS.
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343Wilder-Smith, C. H.; Schindler, D.; Lovblad, K.; Redmond, S. M.; Nirkko, A. Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut 2004, 53, 1595– 1601, DOI: 10.1136/gut.2003.028514343https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2crhtVWrtg%253D%253D&md5=ad6253c554b04976487e1bc95bd701c6Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controlsWilder-Smith C H; Schindler D; Lovblad K; Redmond S M; Nirkko AGut (2004), 53 (11), 1595-601 ISSN:0017-5749.BACKGROUND AND AIMS: Many patients with irritable bowel syndrome (IBS) show intestinal hypersensitivity to distension and sensitisation after repeated intestinal distensions. Abnormalities in endogenous pain inhibitory mechanisms, such as diffuse noxious inhibitory controls (DNIC), may be implicated and were investigated during brain functional magnetic resonance imaging (fMRI). PATIENTS AND METHODS: fMRI was performed in 10 female patients with IBS (five constipated (IBS-C) and five with diarrhoea (IBS-D)) and 10 female healthy controls during rectal balloon distension alone or during activation of DNIC by painful heterotopic stimulation of the foot with ice water. Rectal pain was scored with and without heterotopic stimulation (0 = none, 10 = maximal). RESULTS: Heterotopic stimulation decreased median rectal pain scores significantly in healthy controls (-1.5 (interquartile range -2 to -1); p = 0.001) but not in IBS-C (-0.7 (-1 to 0.5)), IBS-D (-0.5 (-1.5 to 0.5)), or in all IBS patients (0 (-1.5 to 1.3)). Brain activation changes during heterotopic stimulation differed highly significantly between IBS-C, IBS-D, and controls. The main centres affected were the amygdala, anterior cingulate cortex, hippocampus, insula, periaqueductal gray, and prefrontal cortex, which form part of the matrix controlling emotional, autonomic, and descending modulatory responses to pain. CONCLUSIONS: IBS-C and IBS-D appear to have differing abnormal endogenous pain inhibitory mechanisms, involving DNIC and other supraspinal modulatory pathways.
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344Tillisch, K.; Mayer, E. A.; Labus, J. S. Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology 2011, 140, 91– 100, DOI: 10.1053/j.gastro.2010.07.053344https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M%252FlsVaktw%253D%253D&md5=b0b14cfd62049cb1cba0c771498616c2Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndromeTillisch Kirsten; Mayer Emeran A; Labus Jennifer SGastroenterology (2011), 140 (1), 91-100 ISSN:.BACKGROUND AND AIMS: The responsiveness of the central nervous system is altered in patients with irritable bowel syndrome (IBS). However, because of variations in experimental paradigms, analytic techniques, and reporting practices, little consensus exists on brain responses to visceral stimulation. We aimed to identify brain regions consistently activated by supraliminal rectal stimulation in IBS patients and healthy subjects (controls) by performing a quantitative meta-analysis of published studies. METHODS: Significant foci from within-group statistical parametric maps were extracted from published neuroimaging studies that employed rectal distension. Voxel-based activation likelihood estimation was applied, pooling the results and comparing them across groups. RESULTS: Across studies, there was consistent activation in regions associated with visceral afferent processing (ie, thalamus, insula, anterior midcingulate) among IBS patients and controls, but considerable differences in the extent and specific location of foci. IBS patients differed from controls in that there were more consistent activations in regions associated with emotional arousal (pregenual anterior cingulate cortex, amygdala) and activation of a midbrain cluster, a region playing a role in endogenous pain modulation. Controls showed more consistent activation of the medial and lateral prefrontal cortex. CONCLUSIONS: Patients with IBS have greater engagement of regions associated with emotional arousal and endogenous pain modulation, but similar activation of regions involved in processing of visceral afferent information. Controls have greater engagement of cognitive modulatory regions. These results support a role for central nervous system dysregulation in IBS. These findings provide specific targets for guiding development of future neuroimaging protocols to more clearly define altered brain-gut interactions in IBS.
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345Ringel, Y.; Drossman, D. A.; Leserman, J. L.; Suyenobu, B. Y.; Wilber, K.; Lin, W.; Whitehead, W. E.; Naliboff, B. D.; Berman, S.; Mayer, E. A. Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an FMRI study. Gastroenterology 2008, 134, 396– 404, DOI: 10.1053/j.gastro.2007.11.011345https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1c%252Fos1Sjsg%253D%253D&md5=cb28a09dc42eb9b67c0cd64119176158Effect of abuse history on pain reports and brain responses to aversive visceral stimulation: an FMRI studyRingel Yehuda; Drossman Douglas A; Leserman Jane L; Suyenobu Brandall Y; Wilber Kathy; Lin Weili; Whitehead William E; Naliboff Bruce D; Berman Steven; Mayer Emeran AGastroenterology (2008), 134 (2), 396-404 ISSN:.BACKGROUND & AIMS: Abuse history is common in irritable bowel syndrome (IBS) and is associated with greater pain reporting, psychologic distress, and poorer health outcome. These effects may be mediated by enhanced responses to aversive visceral stimuli. We investigated the effects of IBS and abuse history on pain reporting and brain activation in response to rectal distentions. METHODS: Ten female patients with IBS and 10 controls were included. Half of patients in each group reported a history of abuse. Brain functional magnetic resonance imaging (fMRI) images and pain ratings were obtained during rectal distentions. Statistical parametric mapping identified activation in subregions of the dorsal cingulate cortex and covariation with rated pain. RESULTS: (1) Distention-elicited pain correlated with anxiety and activation of the posterior (PCC) and middle (MCC) dorsal cingulate subregions. (2) Subjects with a history of abuse showed greater activation in the left MCC (P = .022; t = 5.61) and PCC (P = .033; t = 5.00) than subjects without abuse. (3) Those with IBS and abuse reported greater pain than all others (P = .004), had more activity in the left MCC (P = .021; t = 5.29) and PCC (P = .049; t = 4.81), and had less activity in the left supragenual anterior cingulate (sACC) (P = .01; t = 4.86). CONCLUSIONS: Pain ratings during rectal distention are associated with activation of dorsal cingulate regions implicated in homeostatic afferent processing, and prior abuse enhances this activation. Patients with IBS and abuse report more pain, greater MCC/PCC activation, and reduced activity of a region implicated in pain inhibition and arousal (sACC). These findings suggest a possible explanation for the clinical observation of greater pain reporting and poorer outcome in IBS patients with a history of abuse.
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346Mayer, E. A.; Bradesi, S.; Chang, L.; Spiegel, B. M.; Bueller, J. A.; Naliboff, B. D. Functional GI disorders: from animal models to drug development. Gut 2008, 57, 384– 404, DOI: 10.1136/gut.2006.101675346https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXjs1ektr8%253D&md5=d9ae30ed1d9dd55c0dd53bea40ec2cabFunctional GI disorders: from animal models to drug developmentMayer, E. A.; Bradesi, S.; Chang, L.; Spiegel, B. M. R.; Bueller, J. A.; Naliboff, B. D.Gut (2008), 57 (3), 384-404CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)A review. Despite considerable efforts by academic researchers and by the pharmaceutical industry, the development of novel pharmacol. treatments for irritable bowel syndrome (IBS) and other functional gastrointestinal (GI) disorders has been slow and disappointing. The traditional approach to identifying and evaluating novel drugs for these symptom-based syndromes has relied on a fairly std. algorithm using animal models, exptl. medicine models and clin. trials. In the current article, the empirical basis for this process is reviewed, focusing on the utility of the assessment of visceral hypersensitivity and GI transit, in both animals and humans, as well as the predictive validity of preclin. and clin. models of IBS for identifying successful treatments for IBS symptoms and IBS-related quality of life impairment. A review of published evidence suggests that abdominal pain, defecation-related symptoms (urgency, straining) and psychol. factors all contribute to overall symptom severity and to health-related quality of life. Correlations between readouts obtained in preclin. and clin. models and resp. symptoms are small, and the ability to predict drug effectiveness for specific as well as for global IBS symptoms is limited. One possible drug development algorithm is proposed which focuses on pharmacol. imaging approaches in both preclin. and clin. models, with decreased emphasis on evaluating compds. in symptom-related animal models, and more rapid screening of promising candidate compds. in man.
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347Labus, J. S.; Osadchiy, V.; Hsiao, E. Y.; Tap, J.; Derrien, M.; Gupta, A.; Tillisch, K.; Le Nevé, B.; Grinsvall, C.; Ljungberg, M. Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysis. Microbiome 2019, 7, 45, DOI: 10.1186/s40168-019-0656-z347https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cbmsl2ksQ%253D%253D&md5=0287762a085c272f8ed0dfd145b78398Evidence for an association of gut microbial Clostridia with brain functional connectivity and gastrointestinal sensorimotor function in patients with irritable bowel syndrome, based on tripartite network analysisLabus Jennifer S; Osadchiy Vadim; Hsiao Elaine Y; Gupta Arpana; Tillisch Kirsten; Mayer Emeran A; Hsiao Elaine Y; Tap Julien; Derrien Muriel; Le Neve Boris; Grinsvall Cecilia; Ohman Lena; Tornblom Hans; Simren Magnus; Ljungberg Maria; Ohman Lena; Simren MagnusMicrobiome (2019), 7 (1), 45 ISSN:.BACKGROUND AND AIMS: Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. METHODS: We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. RESULTS: We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. CONCLUSIONS: In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.
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348Osadchiy, V.; Mayer, E. A.; Gao, K.; Labus, J. S.; Naliboff, B.; Tillisch, K.; Chang, L.; Jacobs, J. P.; Hsiao, E. Y.; Gupta, A. Analysis of brain networks and fecal metabolites reveals brain-gut alterations in premenopausal females with irritable bowel syndrome. Transl Psychiatry 2020, 10, 367, DOI: 10.1038/s41398-020-01071-2348https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXit1Ggtr%252FI&md5=5c89e838387d24a126e6b848354226c2Analysis of brain networks and fecal metabolites reveals brain-gut alterations in premenopausal females with irritable bowel syndromeOsadchiy, Vadim; Mayer, Emeran A.; Gao, Kan; Labus, Jennifer S.; Naliboff, Bruce; Tillisch, Kirsten; Chang, Lin; Jacobs, Jonathan P.; Hsiao, Elaine Y.; Gupta, ArpanaTranslational Psychiatry (2020), 10 (1), 367CODEN: TPRSCF; ISSN:2158-3188. (Nature Research)Alterations in brain-gut-microbiome (BGM) interactions have been implicated in the pathogenesis of irritable bowel syndrome (IBS). Here, we apply a systems biol. approach, leveraging neuroimaging and fecal metabolite data, to characterize BGM interactions that are driving IBS pathophysiol. Fecal samples and resting state fMRI images were obtained from 138 female subjects (99 IBS, 39 healthy controls (HCs)). Partial least-squares discriminant anal. (PLS-DA) was conducted to explore group differences, and partial correlation anal. explored significantly changed metabolites and neuroimaging data. All correlational tests were performed controlling for age, body mass index, and diet; results are reported after FDR correction, with q < 0.05 as significant. Compared to HCs, IBS showed increased connectivity of the putamen with regions of the default mode and somatosensory networks. Metabolite pathways involved in nucleic acid and amino acid metab. differentiated the two groups. Only a subset of metabolites, primarily amino acids, were assocd. with IBS-specific brain changes, including tryptophan, glutamate, and histidine. Histidine was the only metabolite pos. assocd. with both IBS-specific alterations in brain connectivity. Our findings suggest a role for several amino acid metabolites in modulating brain function in IBS. These metabolites may alter brain connectivity directly, by crossing the blood-brain-barrier, or indirectly through peripheral mechanisms. This is the first study to integrate both neuroimaging and fecal metabolite data supporting the BGM model of IBS, building the foundation for future mechanistic studies on the influence of gut microbial metabolites on brain function in IBS.
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349Sarnoff, R. P.; Bhatt, R. R.; Osadchiy, V.; Dong, T.; Labus, J. S.; Kilpatrick, L. A.; Chen, Z.; Subramanyam, V.; Zhang, Y.; Ellingson, B. M. A multi-omic brain gut microbiome signature differs between IBS subjects with different bowel habits. Neuropharmacology 2023, 225, 109381, DOI: 10.1016/j.neuropharm.2022.109381349https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtFyjtr7E&md5=a4fc547b31c0e82f5d2d7cf00b102f64A multi-omic brain gut microbiome signature differs between IBS subjects with different bowel habitsSarnoff, Rachel P.; Bhatt, Ravi R.; Osadchiy, Vadim; Dong, Tien; Labus, Jennifer S.; Kilpatrick, Lisa A.; Chen, Zixi; Subramanyam, Vishvak; Zhang, Yurui; Ellingson, Benjamin M.; Naliboff, Bruce; Chang, Lin; Mayer, Emeran A.; Gupta, ArpanaNeuropharmacology (2023), 225 (), 109381CODEN: NEPHBW; ISSN:0028-3908. (Elsevier B.V.)Alterations of the brain-gut-microbiome system (BGM) have been implicated in the pathophysiol. of irritable bowel syndrome (IBS), yet bowel habit-specific alterations have not been elucidated. In this cross-sectional study, we apply a systems biol. approach to characterize BGM patterns related to predominant bowel habit. Fecal samples and resting state fMRI were obtained from 102 premenopausal women (36 constipation-predominant IBS (IBS-C), 27 diarrhea-predominant IBS (IBS-D), 39 healthy controls (HCs)). Data integration anal. using latent components (DIABLO) was used to integrate data from the phenome, microbiome, metabolome, and resting-state connectome to predict HCs vs IBS-C vs IBS-D. Bloating and visceral sensitivity, distinguishing IBS from HC, were neg. assocd. with beneficial microbes and connectivity involving the orbitofrontal cortex. This suggests that gut interactions may generate aberrant central autonomic and descending pain pathways in IBS. The connection between IBS symptom duration, key microbes, and caudate connectivity may provide mechanistic insight to the chronicity of pain in IBS. Compared to IBS-C and HCs, IBS-D had higher levels of many key metabolites including tryptophan and phenylalanine, and increased connectivity between the sensorimotor and default mode networks; thus, suggestingan influence on diarrhea, self-related thoughts, and pain perception in IBS-D (bottom-up mechanism). IBS-Cs microbiome and metabolome resembled HCs, but IBS-C had increased connectivity in the default mode and salience networks compared to IBS-D, which may indicate importance of visceral signals, suggesting a more top-down BGM pathophysiol. These BGM characteristics highlight possible mechanistic differences for variations in the IBS bowel habit phenome.
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350Berman, S. M.; Naliboff, B. D.; Suyenobu, B.; Labus, J. S.; Stains, J.; Ohning, G.; Kilpatrick, L.; Bueller, J. A.; Ruby, K.; Jarcho, J. Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome. J. Neurosci. 2008, 28, 349– 359, DOI: 10.1523/JNEUROSCI.2500-07.2008350https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1c%252Fit1Gmuw%253D%253D&md5=eca766b1cc3a147861d3fd3b47599965Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndromeBerman Steven M; Naliboff Bruce D; Suyenobu Brandall; Labus Jennifer S; Stains Jean; Ohning Gordon; Kilpatrick Lisa; Bueller Joshua A; Ruby Kim; Jarcho Johanna; Mayer Emeran AThe Journal of neuroscience : the official journal of the Society for Neuroscience (2008), 28 (2), 349-59 ISSN:.Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls. During cued anticipation of distention, activity decreased in the insula, supragenual anterior cingulate cortex (sACC), amygdala, and dorsal brainstem (DBS) of controls. IBS patients showed less anticipatory inactivation. Group differences were significant in the right posterior insula and bilateral DBS. Self-rated measures of negative affect during scanning were higher in patients than controls (p < 0.001), and the anticipatory BOLD decreases in DBS were inversely correlated with these ratings. During subsequent distention, both groups showed activity increases in insula, dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, producing significant group differences in dorsal ACC and DBS. The amplitude of the anticipatory decrease in the pontine portion of DBS was associated with greater activation during distention in right orbitofrontal cortex and bilateral sACC. Both regions have been associated previously with corticolimbic inhibition and cognitive coping. Deficits in preparatory inhibition of DBS, including the locus ceruleus complex and parabrachial nuclei, may interfere with descending corticolimbic inhibition and contribute to enhanced brain responsiveness and perceptual sensitivity to visceral stimuli in IBS.
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351Guleria, A.; Karyampudi, A.; Singh, R.; Khetrapal, C. L.; Verma, A.; Ghoshal, U. C.; Kumar, D. Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging. J. Neurogastroenterol. Motil. 2017, 23, 415– 427, DOI: 10.5056/jnm16148351https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1c3mt1Cmtg%253D%253D&md5=0d7b4ad6f60058559bbf81a7effb6af3Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance ImagingGuleria Anupam; Khetrapal Chunni L; Kumar Dinesh; Karyampudi Arun; Singh Rajan; Verma Abhai; Ghoshal Uday CJournal of neurogastroenterology and motility (2017), 23 (3), 415-427 ISSN:2093-0879.BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. METHODS: Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. RESULTS: IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. CONCLUSIONS: Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain.
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352Ticinesi, A.; Milani, C.; Lauretani, F.; Nouvenne, A.; Mancabelli, L.; Lugli, G. A.; Turroni, F.; Duranti, S.; Mangifesta, M.; Viappiani, A. Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients. Sci. Rep. 2017, 7, 11102, DOI: 10.1038/s41598-017-10734-y352https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cbmvFejsQ%253D%253D&md5=33fed3dc99128e0f02be9c0e18699080Gut microbiota composition is associated with polypharmacy in elderly hospitalized patientsTicinesi Andrea; Lauretani Fulvio; Nouvenne Antonio; Maggio Marcello; Meschi Tiziana; Ticinesi Andrea; Lauretani Fulvio; Nouvenne Antonio; Maggio Marcello; Meschi Tiziana; Milani Christian; Mancabelli Leonardo; Lugli Gabriele Andrea; Turroni Francesca; Duranti Sabrina; Mangifesta Marta; Ferrario Chiara; Ventura Marco; Viappiani AliceScientific reports (2017), 7 (1), 11102 ISSN:.Reduced biodiversity and increased representation of opportunistic pathogens are typical features of gut microbiota composition in aging. Few studies have investigated their correlation with polypharmacy, multimorbidity and frailty. To assess it, we analyzed the fecal microbiota from 76 inpatients, aged 83 ± 8. Microbiome biodiversity (Chao1 index) and relative abundance of individual bacterial taxa were determined by next-generation 16S rRNA microbial profiling. Their correlation with number of drugs, and indexes of multimorbidity and frailty were verified using multivariate linear regression models. The impact of gut microbiota biodiversity on mortality, rehospitalizations and incident sepsis was also assessed after a 2-year follow-up, using Cox regression analysis. We found a significant negative correlation between the number of drugs and Chao1 Index at multivariate analysis. The number of drugs was associated with the average relative abundance of 15 taxa. The drug classes exhibiting the strongest association with single taxa abundance were proton pump inhibitors, antidepressants and antipsychotics. Conversely, frailty and multimorbidity were not significantly associated with gut microbiota biodiversity. Very low Chao1 index was also a significant predictor of mortality, but not of rehospitalizations and sepsis, at follow-up. In aging, polypharmacy may thus represent a determinant of gut microbiota composition, with detrimental clinical consequences.
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353Chopra, K.; Kumar, B.; Kuhad, A. Pathobiological targets of depression. Expert Opin. Ther. Targets 2011, 15, 379– 400, DOI: 10.1517/14728222.2011.553603353https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M3kvFKmtQ%253D%253D&md5=3f82d50c4e7e1d996d8e92bfadffc3fbPathobiological targets of depressionChopra Kanwaljit; Kumar Baldeep; Kuhad AnuragExpert opinion on therapeutic targets (2011), 15 (4), 379-400 ISSN:.INTRODUCTION: Depression is one of the most prevalent and life-threatening forms of mental illness associated with significant disability and mortality. About 21% of the world's population is affected by depression. AREAS COVERED: The various pathological factors involved in depression are: monoamine hypothesis, neurotransmitter receptor hypothesis, neurotrophic factor hypothesis, hypothalamic-pituitary-adrenal (HPA) dysregulation, oxidative stress, cytokine hypothesis and NO pathway. Recent drug therapies used to treat depression include: selective serotonin re-uptake inhibitors, norepinephrine and dopamine re-uptake inhibitors and several herbal drugs. The present review focuses on recently unraveled pathogenetic hypotheses and therapeutics of mental depression. Moreover, various evaluation models for antidepressants are discussed. EXPERT OPINION: Stress can be considered as a major contributor to the development of depressive disorder due to the dysregulation of HPA axis. Cytokine effects on behavior are believed to be related in part to their effects on neurotransmitter and neuropeptide function, synaptic plasticity and neuroendocrine function. Although there are multiple pathways that are involved in the pathogenesis of depression, the current antidepressants mainly target monoaminergic pathway. However, the therapeutic potential of other pathways is still under investigation. Drugs targeting NO, cytokines and the kynurenine acid pathway might be the drugs of choice in near future.
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354Dinan, T. G.; Cryan, J. F. Gut-brain axis in 2016: Brain-gut-microbiota axis - mood, metabolism and behaviour. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 69– 70, DOI: 10.1038/nrgastro.2016.200354https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjs1KjtA%253D%253D&md5=0089b5cedcf0749bac10b7d445a94534Gut-brain axis in 2016 Brain-gut-microbiota axis - mood, metabolism and behaviourDinan, Timothy G.; Cryan, John F.Nature Reviews Gastroenterology & Hepatology (2017), 14 (2), 69-70CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)A review. In 2016, key studies have increased our understanding of the part played by the brain-gut-microbiota axis in disorders as diverse as depression, obesity and autism spectrum disorder. The data indicate that alterations in gut-microbial compn. can substantially affect central physiol., and that transplantation of the gut microbiota can transfer a behavioral or physiol. phenotype.
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355Foster, J. A.; McVey Neufeld, K. A. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013, 36, 305– 312, DOI: 10.1016/j.tins.2013.01.005355https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFSgsbw%253D&md5=fc711bb33d5e2e851f9465d2055a0e3cGut-brain axis: how the microbiome influences anxiety and depressionFoster, Jane A.; McVey Neufeld, Karen-AnneTrends in Neurosciences (2013), 36 (5), 305-312CODEN: TNSCDR; ISSN:0166-2236. (Elsevier Ltd.)A review. Within the first few days of life, humans are colonized by commensal intestinal microbiota. Here, we review recent findings showing that microbiota are important in normal healthy brain function. The authors also discuss the relation between stress and microbiota, and how alterations in microbiota influence stress-related behaviors. New studies show that bacteria, including commensal, probiotic, and pathogenic bacteria, in the gastrointestinal (GI) tract can activate neural pathways and central nervous system (CNS) signaling systems. Ongoing and future animal and clin. studies aimed at understanding the microbiota-gut-brain axis may provide novel approaches for prevention and treatment of mental illness, including anxiety and depression.
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356Halkjær, S. I.; Christensen, A. H.; Lo, B. Z. S.; Browne, P. D.; Günther, S.; Hansen, L. H.; Petersen, A. M. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. Gut 2018, 67, 2107– 2115, DOI: 10.1136/gutjnl-2018-316434356https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXktVGkt7k%253D&md5=52cf8373999bc1f9b2f560e0b8fbfa34Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled studyHalkjaer, Sofie Ingdam; Christensen, Alice Hoejer; Lo, Bobby Zhao Sheng; Browne, Patrick Denis; Gunther, Stig; Hansen, Lars Hestbjerg; Petersen, Andreas MunkGut (2018), 67 (12), 2107-2115CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective IBS is assocd. with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a pos. effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clin. outcome in patients with IBS. Design We performed this study in 52 adult patients with moderate-to-severe IBS. Study visits were performed at baseline, 1, 3 and 6 mo, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected. Results A significant difference in improvement in IBS-SSS score was obsd. 3 mo after treatment (p = 0.012) favoring placebo. This was similar for IBSQoL data after 3 mo (p = 0.003) favoring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not. Conclusion In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 mo. Altering the gut microbiota is not enough to obtain clin. improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.
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357Holvoet, T.; Joossens, M.; Wang, J.; Boelens, J.; Verhasselt, B.; Laukens, D.; van Vlierberghe, H.; Hindryckx, P.; De Vos, M.; De Looze, D. Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating. Gut 2017, 66, 980– 982, DOI: 10.1136/gutjnl-2016-312513357https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s3psFGjuw%253D%253D&md5=830da54674360cdfa132380186db373bAssessment of faecal microbial transfer in irritable bowel syndrome with severe bloatingHolvoet Tom; Laukens Debby; van Vlierberghe Hans; Hindryckx Pieter; De Vos Martine; De Looze Danny; Joossens Marie; Wang Jun; Raes Jeroen; Joossens Marie; Wang Jun; Raes Jeroen; Joossens Marie; Boelens Jerina; Verhasselt BrunoGut (2017), 66 (5), 980-982 ISSN:.There is no expanded citation for this reference.
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358Mizuno, S.; Masaoka, T.; Naganuma, M.; Kishimoto, T.; Kitazawa, M.; Kurokawa, S.; Nakashima, M.; Takeshita, K.; Suda, W.; Mimura, M. Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel Syndrome. Digestion 2017, 96, 29– 38, DOI: 10.1159/000471919358https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cnpslSluw%253D%253D&md5=0f7d0f0446ba20074bd9d8f2b0e99d49Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel SyndromeMizuno Shinta; Masaoka Tatsuhiro; Naganuma Makoto; Kishimoto Taishiro; Kitazawa Momoko; Kurokawa Shunya; Nakashima Moeko; Takeshita Kozue; Suda Wataru; Mimura Masaru; Hattori Masahira; Kanai TakanoriDigestion (2017), 96 (1), 29-38 ISSN:.BACKGROUND/AIMS: Dysbiosis is associated with various systemic disorders including irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) might restore intestinal microbial balance. The study aimed to determine the safety and efficacy of FMT in IBS patients, as well as also positive predictors for FMT. METHODS: This was a single-arm, open-label study. Eligible patients were diagnosed based on Rome III Diagnostic Criteria. Fecal materials were administered to the patient via colonoscopy. The primary end point was a change in the Bristol stool form scale at 4 weeks after FMT. Recovery to types 3-4 was considered a clinical response. The secondary end point was a change in intestinal microbiota and psychological status using the Hamilton Rating Scale. RESULTS: Ten patients were enrolled. Six patients achieved a clinical response. The diversity of patients 4 weeks after FMT increased significantly compared with patients before FMT, and that of responding patients was significantly higher than non-responder patients. The abundance of Bifidobacterium in effective donors was significantly higher than in ineffective donors and patients. Psychological status of all patients was significantly improved after FMT. CONCLUSIONS: FMT for patients with IBS is safe, and relatively effective. Bifidobacterium-rich fecal donor may be a positive predictor for successful FMT. Key Summary: (1) Dysbiosis is associated with various gastrointestinal disorders including IBS. (2) FMT has potential to restore intestinal microbial balance. (3) We showed that FMT improved stool form and psychological status of IBS patients. (4) Bifidobacterium-rich donor efficiently induced symbiosis in IBS patients.
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359Zoller, V.; Laguna, A. L.; Prazeres Da Costa, O.; Buch, T.; Göke, B.; Storr, M. Fecal microbiota transfer (FMT) in a patient with refractory irritable bowel syndrome. Dtsch. Med. Wochenschr. 2015, 140, 1232– 1236, DOI: 10.1055/s-0041-103798359https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC287itVyqsg%253D%253D&md5=5d8b7133de58d293afa3b21677da0483Fecal microbiota transfer (FMT) in a patient with refractory irritable bowel syndromeZoller Verena; Laguna Anna-Lena; Goke Burkhard; Storr Martin; Prazeres Da Costa Olivia; Buch ThorstenDeutsche medizinische Wochenschrift (1946) (2015), 140 (16), 1232-6 ISSN:.Irritable bowel syndrome is a disorder of the gastrointestinal tract with unknown etiology. Recent clinical data support a link between changes in fecal microbiota with decreased biodiversity and the development of irritable bowel syndrome. Whether these changes of the microbiota are caused by the disease or whether they develop during the course of the disease remains unclear. Several studies demonstrated that fecal microbiota transfer (FMT) successfully attenuates Clostridium difficile infection by restoring the disturbed bacterial flora of the gut and case reports suggest that FMT may relief symptoms in patients with irritable bowel syndrome (IBS). Here we report a 47-year-old male patient with longstanding refractory diarrhea predominant IBS, who was successfully treated with a single FMT. The beneficial effect on the patient's symptoms was associated with changes of the stool microbiome. Post-FMT the recipient's microbiome resembled the donor's microbiome.
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360Drago, L.; Meroni, G.; Pistone, D.; Pasquale, L.; Milazzo, G.; Monica, F.; Aragona, S.; Ficano, L.; Vassallo, R. Evaluation of main functional dyspepsia symptoms after probiotic administration in patients receiving conventional pharmacological therapies. J. Int. Med. Res. 2021, 49, 300060520982657, DOI: 10.1177/0300060520982657There is no corresponding record for this reference.
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361Potter, M. D. E.; Talley, N. J. Editorial: new insights into the global prevalence of uninvestigated and functional dyspepsia. Aliment. Pharmacol. Ther. 2020, 52 (8), 1407– 1408, DOI: 10.1111/apt.16059361https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3s7mtlyrsg%253D%253D&md5=abc5cb19b34b96873006f9c80015fb5cEditorial: new insights into the global prevalence of uninvestigated and functional dyspepsiaPotter Michael D E; Talley Nicholas J; Potter Michael D E; Talley Nicholas J; Potter Michael D E; Talley Nicholas JAlimentary pharmacology & therapeutics (2020), 52 (8), 1407-1408 ISSN:.There is no expanded citation for this reference.
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362Zhong, L.; Shanahan, E. R.; Raj, A.; Koloski, N. A.; Fletcher, L.; Morrison, M.; Walker, M. M.; Talley, N. J.; Holtmann, G. Dyspepsia and the microbiome: time to focus on the small intestine. Gut 2017, 66, 1168– 1169, DOI: 10.1136/gutjnl-2016-312574362https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhtFGrt7fN&md5=b5b172b677fe7570bad763a4dd648e3fDyspepsia and the microbiome: time to focus on the small intestineZhong, Laurie; Shanahan, Erin R.; Raj, Ashok; Koloski, Natasha A.; Fletcher, Linda; Morrison, Mark; Walker, Marjorie M.; Talley, Nicholas J.; Holtmann, GeraldGut (2017), 66 (6), 1168-1170CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)A review. This article describes about relative abundance of bacterial genera in small intestine differences between patients with functional dyspepsia and controls.
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363Vanheel, H.; Vicario, M.; Vanuytsel, T.; Van Oudenhove, L.; Martinez, C.; Keita, Å. V.; Pardon, N.; Santos, J.; Söderholm, J. D.; Tack, J. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014, 63, 262– 271, DOI: 10.1136/gutjnl-2012-303857363https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXkslartro%253D&md5=94d117d7065c2e08ef8ff9eeb42f879dImpaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsiaVanheel, Hanne; Vicario, Maria; Vanuytsel, Tim; Van Oudenhove, Lukas; Martinez, Cristina; Keita, Aasa V.; Pardon, Nicolas; Santos, Javier; Soederholm, Johan D.; Tack, Jan; Farre, RicardGut (2014), 63 (2), 262-271CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiol. of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial elec. resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Nos. of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochem. Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addn., abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterized by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant assocn. between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiol. mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.
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364Liu, X. J.; Xie, W. R.; Wu, L. H.; Ye, Z. N.; Zhang, X. Y.; Zhang, R.; He, X. X. Changes in oral flora of patients with functional dyspepsia. Sci. Rep. 2021, 11, 8089, DOI: 10.1038/s41598-021-87600-5364https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXptFOrsL0%253D&md5=abd93f1ee6539e51861d0b45caa0663bChanges in oral flora of patients with functional dyspepsiaLiu, Xu-juan; Xie, Wen-rui; Wu, Li-hao; Ye, Zhi-ning; Zhang, Xue-yuan; Zhang, Ran; He, Xing-xiangScientific Reports (2021), 11 (1), 8089CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)To explore the changes in oral flora in people with functional dyspepsia (FD). Unstimulated saliva was collected from 21 FD patients diagnosed according to the Rome IV criteria and from 12 healthy controls (HCs) for 16SrRNA sequencing. The pH of saliva samples and community periodontal index (CPI) were tested. The prevalence of small intestinal bacterial overgrowth (SIBO) was obtained by the methane-and hydrogen-based breath test. At the phylum level, FD patients had a higher relative abundance of Spirochaetes and a lower relative abundance of Fusobacteria, TM7 and Proteobacteria than HCs (p < 0.01). In the saliva, Kingella and Abiotrophia genus levels showed significant changes between the FD and HC groups (p < 0.01). Salivary species level marker Intermedia was significantly different between FD and HC groups (p < 0.01). The oral pH of FD patients was higher than that of HCs (p < 0.01). The mean CPI of the FD group was 1.52 and that of the HC group was 0.17 (p < 0.01). Moreover, 71.4% of the FD group was pos. for SIBO. The oral flora of FD patients was different from that of HCs. Spirochaetes, Kingella, Abiotrophia, and Intermedia may be diagnostic indicators of FD.
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365Aro, P.; Talley, N. J.; Johansson, S. E.; Agréus, L.; Ronkainen, J. Anxiety Is Linked to New-Onset Dyspepsia in the Swedish Population: A 10-Year Follow-up Study. Gastroenterology 2015, 148, 928– 937, DOI: 10.1053/j.gastro.2015.01.039365https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MrhvV2htw%253D%253D&md5=cf3f0c9b39d4819f0a68c1beff953d4eAnxiety Is Linked to New-Onset Dyspepsia in the Swedish Population: A 10-Year Follow-up StudyAro Pertti; Talley Nicholas J; Johansson Sven-Erik; Agreus Lars; Ronkainen JukkaGastroenterology (2015), 148 (5), 928-37 ISSN:.BACKGROUND & AIMS: Functional dyspepsia (FD) is associated with anxiety but it is not clear if one causes the other. We investigated whether anxiety and depression precede the onset of FD (based on the modified Rome III criteria) and gastroesophageal reflux symptoms (GERS) in a population-based follow-up study. METHODS: Participants from the Kalixanda study (n = 3000), randomly selected from the national population register of Sweden, were given the validated Abdominal Symptom Questionnaire 1998-2001; 1000 of these participants then were selected randomly to undergo esophagogastroduodenoscopy and were given the Abdominal Symptom Questionnaire along with the Hospital Anxiety and Depression Scale questionnaire. All eligible subjects who underwent endoscopy (n = 887) were invited to participate in a follow-up study in June-August 2010 and were given the same questionnaires. Data were analyzed by logistic regression. RESULTS: Of the 703 subjects who completed the follow-up questionnaires (79.3%); 110 were found to have FD at baseline (15.6%) and 93 at the follow-up examination (13.3%); 48 of these were new cases of FD. GERS without organic disease was reported by 273 individuals (38.8%) at baseline and by 280 at follow-up examination (39.8%); 93 cases were new. Major anxiety was associated with FD at the follow-up evaluation (odds ratio [OR], 6.30; 99% confidence interval [CI], 1.64-24.16). Anxiety was associated with postprandial distress syndrome at baseline (OR, 4.83; 99% CI, 1.24-18.76) and at the follow-up examination (OR, 8.12; 99% CI, 2.13-30.85), but not with epigastric pain syndrome. Anxiety at baseline was associated with new-onset FD at the follow-up examination (OR, 7.61; 99% CI, 1.21-47.73), but not with GERS. CONCLUSIONS: In a study of the Swedish population, anxiety at baseline, but not depression, increased the risk for development of FD by 7.6-fold in the next 10 years. Anxiety did not affect risk for GERS.
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366Van Oudenhove, L.; Aziz, Q. The role of psychosocial factors and psychiatric disorders in functional dyspepsia. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 158– 167, DOI: 10.1038/nrgastro.2013.10366https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3szjt12gsg%253D%253D&md5=93003eb3730cc03c84bfb391e3a24861The role of psychosocial factors and psychiatric disorders in functional dyspepsiaVan Oudenhove Lukas; Aziz QasimNature reviews. Gastroenterology & hepatology (2013), 10 (3), 158-67 ISSN:.In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.
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367Hannibal, K. E.; Bishop, M. D. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys. Ther. 2014, 94, 1816– 1825, DOI: 10.2522/ptj.20130597367https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cbjtlGisg%253D%253D&md5=7ea82a617a15f017a88bc9d54a27b67eChronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitationHannibal Kara E; Bishop Mark DPhysical therapy (2014), 94 (12), 1816-25 ISSN:.Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to facilitate treatment, prevent chronic disability, and improve quality of life.
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368Koloski, N. A.; Jones, M.; Kalantar, J.; Weltman, M.; Zaguirre, J.; Talley, N. J. The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut 2012, 61, 1284– 1290, DOI: 10.1136/gutjnl-2011-300474368https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC38vgtFOnsA%253D%253D&md5=983db78675e60e2b09acbcf781152011The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based studyKoloski N A; Jones M; Kalantar J; Weltman M; Zaguirre J; Talley N JGut (2012), 61 (9), 1284-90 ISSN:.OBJECTIVE: Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain-gut mechanism in FGIDs. DESIGN: Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. RESULTS: Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up. CONCLUSIONS: The central nervous system and gut interact bidirectionally in FGIDs.
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369Cryan, J. F.; Dinan, T. G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 2012, 13, 701– 712, DOI: 10.1038/nrn3346369https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlamurvN&md5=d88f108ce34ee7792c15f3d7afb1b054Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviourCryan, John F.; Dinan, Timothy G.Nature Reviews Neuroscience (2012), 13 (10), 701-712CODEN: NRNAAN; ISSN:1471-003X. (Nature Publishing Group)A review. Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biol. Studies are revealing how variations and changes in the compn. of the gut microbiota influence normal physiol. and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS - possibly through neural, endocrine and immune pathways - and thereby influences brain function and behavior. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
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370Browning, K. N.; Travagli, R. A. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol 2014, 4, 1339– 1368, DOI: 10.1002/cphy.c130055370https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MzhtFyqug%253D%253D&md5=cc4c30fb531fd094275f297a9df79bd4Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functionsBrowning Kirsteen N; Travagli R AlbertoComprehensive Physiology (2014), 4 (4), 1339-68 ISSN:.Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathetic nervous system exerts a predominantly inhibitory effect upon GI muscle and provides a tonic inhibitory influence over mucosal secretion while, at the same time, regulates GI blood flow via neurally mediated vasoconstriction. The parasympathetic nervous system, in contrast, exerts both excitatory and inhibitory control over gastric and intestinal tone and motility. Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the higher CNS centers influence homeostatic control as well as cognitive and behavioral functions. This review will describe the basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways. The role of CNS-centered reflexes in the regulation of GI functions will be discussed as will modulation of these reflexes under both physiological and pathophysiological conditions. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide these answers.
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371Barberio, B.; Judge, C.; Savarino, E. V.; Ford, A. C. Global prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2021, 6, 638– 648, DOI: 10.1016/S2468-1253(21)00111-4371https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c7ksFWktg%253D%253D&md5=1364c3612427e99e5ee47aabeb4df7baGlobal prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysisBarberio Brigida; Savarino Edoardo V; Judge Ciaran; Ford Alexander CThe lancet. Gastroenterology & hepatology (2021), 6 (8), 638-648 ISSN:.BACKGROUND: Functional constipation is a common functional bowel disorder in the community, which has a varying prevalence across cross-sectional surveys. We did a contemporaneous systematic review and meta-analysis of studies using comparable methodology and all iterations of the Rome criteria to estimate the global prevalence of functional constipation. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Embase Classic from Jan 1, 1990, to Dec 31, 2020, to identify population-based cross-sectional studies comprising at least 50 participants that reported the prevalence of functional constipation in adults (age 18 years and older) according to Rome I, II, III, or IV criteria. We excluded studies that reported the prevalence of functional constipation in convenience samples. We extracted prevalence estimates of functional constipation from eligible studies, according to the study criteria used to define it. For each study, we extracted data for country; method of data collection; criteria used to define functional constipation; whether the study used the Rome I, II, III, or IV diagnostic questionnaires or approximated these definitions of the condition using another questionnaire; the total number of participants providing complete data; age; the number of participants with the condition; the number of male and female participants; and the number of male and female participants with the condition. We calculated pooled prevalence, odds ratios (OR), and 95% CIs. FINDINGS: Of 8174 citations evaluated, 45 studies fulfilled the eligibility criteria, representing 80 separate populations and comprising 275 260 participants. The pooled prevalence of functional constipation was 15·3% (95% CI 8·1-24·4, I(2)=99·4%) in studies using the Rome I criteria, 11·2% (7·9-14·9; I(2)=99·6%) in studies that used Rome II criteria, 10·4% (6·5-14·9; I(2)=99·8%) in those that used Rome III criteria, and 10·1% (8·7-11·6; I(2)=98·2%) when Rome IV criteria were used. Prevalence of functional constipation was higher in women, irrespective of the Rome criteria used (OR 2·40 [95% CI 2·02-2·86] for Rome I, 1·94 [1·46-2·57] for Rome II, and 2·32 [1·85-2·92] for Rome III; no studies using Rome IV criteria reported prevalence by sex). There was significant heterogeneity between studies in all of our analyses, which persisted even when the same criteria were applied and similar methodologies used. INTERPRETATION: Even when uniform symptom-based criteria are used to define the presence of functional constipation, prevalence varies between countries. Thus, environmental, cultural, ethnic, dietary, or genetic factors can influence reporting of symptoms. Future studies should aim to elucidate reasons for this geographical variability. FUNDING: None.
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372Vriesman, M. H.; Koppen, I. J. N.; Camilleri, M.; Di Lorenzo, C.; Benninga, M. A. Management of functional constipation in children and adults. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 21– 39, DOI: 10.1038/s41575-019-0222-y372https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3MjlsFKntA%253D%253D&md5=2e096fc7ff8299c85771d44fb87110afManagement of functional constipation in children and adultsVriesman Mana H; Koppen Ilan J N; Benninga Marc A; Camilleri Michael; Di Lorenzo CarloNature reviews. Gastroenterology & hepatology (2020), 17 (1), 21-39 ISSN:.Functional constipation is common in children and adults worldwide. Functional constipation shows similarities in children and adults, but important differences also exist regarding epidemiology, symptomatology, pathophysiology, diagnostic workup and therapeutic management. In children, the approach focuses on the behavioural nature of the disorder and the initial therapeutic steps involve toilet training and laxatives. In adults, management focuses on excluding an underlying cause and differentiating between different subtypes of functional constipation - normal transit, slow transit or an evacuation disorder - which has important therapeutic consequences. Treatment of adult functional constipation involves lifestyle interventions, pelvic floor interventions (in the presence of a rectal evacuation disorder) and pharmacological therapy. When conventional treatments fail, children and adults are considered to have intractable functional constipation, a troublesome and distressing condition. Intractable constipation is managed with a stepwise approach and in rare cases requires surgical interventions such as antegrade continence enemas in children or colectomy procedures for adults. New drugs, including prokinetic and prosecretory agents, and surgical strategies, such as sacral nerve stimulation, have the potential to improve the management of children and adults with intractable functional constipation.
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373Zhuang, M.; Shang, W.; Ma, Q.; Strappe, P.; Zhou, Z. Abundance of Probiotics and Butyrate-Production Microbiome Manages Constipation via Short-Chain Fatty Acids Production and Hormones Secretion. Mol. Nutr. Food Res. 2019, 63, e1801187, DOI: 10.1002/mnfr.201801187373https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitVSlsb%252FK&md5=cf656b161ae6883d058bd6143ae1a23bAbundance of Probiotics and Butyrate-Production Microbiome Manages Constipation via Short-Chain Fatty Acids Production and Hormones SecretionZhuang, Min; Shang, Wenting; Ma, Qiuchen; Strappe, Padraig; Zhou, ZhongkaiMolecular Nutrition & Food Research (2019), 63 (23), 1801187CODEN: MNFRCV; ISSN:1613-4125. (Wiley-VCH Verlag GmbH & Co. KGaA)Scope : The characteristics of gut microbiota and host metab. are hypothesized to be assocd. with constipation status, but the regulation mechanism is not fully understood. Thus, the current study investigates the effect of constipation symptoms on gut functionality following the modulation of gut microbiota and metabolites via dietary fiber intervention. Methods and results : Constipation causes a significantly reduced short-chain fatty acids (SCFAs) prodn. and a higher level of iso-butyrate. The feces of constipated people are characterized with inhibited Faecalibacterium, Ruminococcaceae and Roseburia abundance. Desulfovibrionaceae is identified to be an important endotoxin producer in constipated patients, and a butyrate-enriched SCFAs profile achieved by dietary fiber supplement accelerates gastrointestinal transit and increases the thickness of the mucosal layer, possibly through triggering the secretion of colonic hormones and enhancing the expression of tight junction proteins for maintaining intestinal barrier integrity. More importantly, an interacting regulatory mechanism among SCFAs, in particular butyrate and propionate, may be involved in signaling between the microbiome and host cells in the colon. Conclusion : Gut microbiota, characterized with enriched butyrate-producing and depressed Desulfovibrionaceae bacteria, attenuates constipation symptoms through promoting intestinal hormones secretion and maintaining gut barrier integrity.
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374Attaluri, A.; Jackson, M.; Valestin, J.; Rao, S. S. Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS. Am. J. Gastroenterol. 2010, 105, 1407– 1411, DOI: 10.1038/ajg.2009.655374https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3czpsVKjsA%253D%253D&md5=c85e203042559f239b4bc67b33010d76Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBSAttaluri Ashok; Jackson Michelle; Valestin Jessica; Rao Satish S CThe American journal of gastroenterology (2010), 105 (6), 1407-11 ISSN:.OBJECTIVES: About 35% of humans have methane-producing gut flora. Methane-producing irritable bowel syndrome (IBS) subjects are generally constipated. In animal models, methane infusion slows intestinal transit. Whether methanogenic flora alters colonic transit or stool characteristics and its relationship to constipation is unclear. The aim of this study was to examine the prevalence and association of methanogenic flora in patients with slow transit (ST) constipation and normal transit (NT) constipation and non-constipated controls. METHODS: Ninety-six consecutive subjects with chronic constipation (CC) (Rome III) were evaluated with radio-opaque marker (ROM) transit studies and were classified as ST (>20% ROM retention) or NT. All constipated subjects and 106 non-constipated controls underwent breath tests to assess methane production. Baseline CH4 of >or=3 p.p.m. was used to define presence of methanogenic flora. Stool frequency and consistency were assessed using a prospective stool diary. Correlation analyses were performed. RESULTS: Forty-eight subjects had ST and 48 had NT. Prevalence of methanogenic flora was higher (P<0.05) in ST (75%) compared to NT (44%) or controls (28%). ST patients had higher methane production compared to NT and controls (P<0.05). NT patients also produced more methane compared to controls (P<0.05). There was moderate(P<0.05) correlation among baseline, peak, and area under the curve (AUC) of methane response with colonic transit but not with stool characteristics. CONCLUSIONS: Presence of methanogenic flora is associated with CC. Methane production after carbohydrate challenge and its prevalence were higher in ST than NT, although stool characteristics were similar in both groups. Methane production correlated with colonic transit, suggesting an association with stool transport but not with stool characteristics.
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375Chen, Y.; Wu, T.; Lu, W.; Yuan, W.; Pan, M.; Lee, Y. K.; Zhao, J.; Zhang, H.; Chen, W.; Zhu, J. Predicting the Role of the Human Gut Microbiome in Constipation Using Machine-Learning Methods: A Meta-Analysis. Microorganisms 2021, 9, 2149, DOI: 10.3390/microorganisms9102149375https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXivVWlu7nE&md5=8adcc0f5cee52d46f6a2f211545ddc13Predicting the Role of the Human Gut Microbiome in Constipation Using Machine-Learning Methods: A Meta-AnalysisChen, Yutao; Wu, Tong; Lu, Wenwei; Yuan, Weiwei; Pan, Mingluo; Lee, Yuan-Kun; Zhao, Jianxin; Zhang, Hao; Chen, Wei; Zhu, Jinlin; Wang, HongchaoMicroorganisms (2021), 9 (10), 2149CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Constipation is a common condition that affects the health and the quality of life of patients. Recent studies have suggested that the gut microbiome is assocd. with constipation, but these studies were mainly focused on a single research cohort. Thus, we aimed to construct a classification model based on fecal bacterial and identify the potential gut microbes' biomarkers. We collected 3056 fecal amplicon sequence data from five research cohorts. The data were subjected to a series of analyzes, including alpha- and beta-diversity analyzes, phylogenetic profiling analyzes, and systematic machine learning to obtain a comprehensive understanding of the assocn. between constipation and the gut microbiome. The alpha diversity of the bacterial community compn. was higher in patients with constipation. Beta diversity anal. evidenced significant partitions between the two groups on the base of gut microbiota compn. Further, machine learning based on feature selection was performed to evaluate the utility of the gut microbiome as the potential biomarker for constipation. The Gradient Boosted Regression Trees after chi2 feature selection was the best model, exhibiting a validation performance of 70.7% . We constructed an accurate constipation discriminant model and identified 15 key genera, including Serratia, Dorea, and Aeromonas, as possible biomarkers for constipation.
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376Tian, H.; Ye, C.; Yang, B.; Cui, J.; Zheng, Z.; Wu, C.; Zhou, S.; Lv, X.; Qin, N.; Qin, H. Gut Metagenome as a Potential Diagnostic and Predictive Biomarker in Slow Transit Constipation. Front. Med. 2022, 8, 777961, DOI: 10.3389/fmed.2021.777961There is no corresponding record for this reference.
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377Sartor, R. B. Optimal sampling of the intestinal microbiota for research. Nature Reviews Gastroenterology & Hepatology 2015, 12, 253– 254, DOI: 10.1038/nrgastro.2015.46377https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MnntFWrsg%253D%253D&md5=46baa3f95fc32b226f0e214977f52e8dGut microbiota: Optimal sampling of the intestinal microbiota for researchSartor R BalfourNature reviews. Gastroenterology & hepatology (2015), 12 (5), 253-4 ISSN:.There is no expanded citation for this reference.
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378Swidsinski, A.; Loening-Baucke, V.; Verstraelen, H.; Osowska, S.; Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 2008, 135, 568– 579, DOI: 10.1053/j.gastro.2008.04.017378https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1crgslWhsQ%253D%253D&md5=cbafe518ff3d830ea9bdd165cdaecaebBiostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrheaSwidsinski Alexander; Loening-Baucke Vera; Verstraelen Hans; Osowska Sylwia; Doerffel YvonneGastroenterology (2008), 135 (2), 568-79 ISSN:.BACKGROUND & AIMS: Dysbiosis is a key component of intestinal disorders. Our aim was to quantitatively access the biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea and evaluate the responses to Saccharomyces boulardii treatment. METHODS: We investigated punched fecal cylinders from 20 patients with chronic idiopathic diarrhea and 20 healthy controls using fluorescence in situ hybridization. Fluctuations in assembly of 11 bacterial groups were monitored weekly for 3 weeks before, during, and after oral S boulardii supplementation. RESULTS: The structural organization of fecal microbiota in healthy subjects was stable and unaffected by S boulardii. The assembly of fecal microbiota in idiopathic diarrhea was markedly different, characterized by mucus depositions within feces; mucus septa and striae; marked reduction in concentrations of habitual Eubacterium rectale, Bacteroides, and Faecalibacterium prausnitzii groups; suppression of bacterial fluorescence in the center of the feces; increased concentrations and spatial shift of mucotrop bacteria to the fecal core; and increased concentrations of occasional bacteria. Except for elevated concentrations of some occasional bacterial groups, all parameters typical for diarrhea improved significantly with S boulardii treatment and most changes persisted after cessation of therapy. The improvement of the fecal microbiota was accompanied by partial (40%) and complete normalization (30%) of the diarrheal symptoms. CONCLUSIONS: The fecal microbiota is highly structured. Fluorescence in situ hybridization analysis allowed us to quantitatively study the dysbiotic changes. S boulardii significantly improved the fecal biostructure in patients with diarrhea but had no influence on the feces in healthy subjects.
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379Durbán, A.; Abellán, J. J.; Jiménez-Hernández, N.; Salgado, P.; Ponce, M.; Ponce, J.; Garrigues, V.; Latorre, A.; Moya, A. Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome. Environ. Microbiol. Rep. 2012, 4, 242– 247, DOI: 10.1111/j.1758-2229.2012.00327.x379https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmsVKit7Y%253D&md5=72b2d693eeec0219ab30c2fde6edb68fStructural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndromeDurban, Ana; Abellan, Juan J.; Jimenez-Hernandez, Nuria; Salgado, Patricia; Ponce, Marta; Ponce, Julio; Garrigues, Vicente; Latorre, Amparo; Moya, AndresEnvironmental Microbiology Reports (2012), 4 (2), 242-247CODEN: EMRNAG; ISSN:1758-2229. (Wiley-Blackwell)Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in western countries. Previous studies on IBS, mostly based on fecal samples, suggest alterations in the intestinal microbiota. However, no consensus has been reached regarding the assocn. between specific bacteria and IBS. We explore the alterations of intestinal bacterial communities in IBS using massive sequencing of amplified 16S rRNA genes. Mucosal biopsies of the ascending and descending colon and feces from 16 IBS patients and 9 healthy controls were analyzed. Strong inter-individual variation was obsd. in the compn. of the bacterial communities in both patients and controls. These communities showed less diversity in IBS cases. There were larger differences in the microbiota compn. between biopsies and feces than between patients and controls. We found a few over-represented and under-represented taxa in IBS cases with respect to controls. The detected alterations varied by site, with no changes being consistent across sample types.
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380Parthasarathy, G.; Chen, J.; Chen, X.; Chia, N.; O’Connor, H. M.; Wolf, P. G.; Gaskins, H. R.; Bharucha, A. E. Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation. Gastroenterology 2016, 150, 367– 379.e1, DOI: 10.1053/j.gastro.2015.10.005380https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28zhsFChuw%253D%253D&md5=cf6cebd32bf979c44e3632c67faf0a16Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic ConstipationParthasarathy Gopanandan; Chen Jun; Chia Nicholas; Chen Xianfeng; O'Connor Helen M; Wolf Patricia G; Gaskins H Rex; Bharucha Adil EGastroenterology (2016), 150 (2), 367-79.e1 ISSN:.BACKGROUND & AIMS: In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. METHODS: Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). RESULTS: Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. CONCLUSIONS: After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation.
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381Procházková, N.; Falony, G.; Dragsted, L. O.; Licht, T. R.; Raes, J.; Roager, H. M. Advancing human gut microbiota research by considering gut transit time. Gut 2023, 72, 180– 191, DOI: 10.1136/gutjnl-2022-328166381https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XjtFKms7vO&md5=db48f64ad3b3aa7bf209854a1bdc6aebAdvancing human gut microbiota research by considering gut transit timeProchazkova, Nicola; Falony, Gwen; Dragsted, Lars Ove; Licht, Tine Rask; Raes, Jeroen; Roager, Henrik M.Gut (2023), 72 (1), 180-191CODEN: GUTTAK; ISSN:0017-5749. (BMJ)A review. Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota compn. and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota compn. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota compn., diversity and metab. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet-microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.
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382Hosseinzadeh, S. T.; Poorsaadati, S.; Radkani, B.; Forootan, M. Psychological disorders in patients with chronic constipation. Gastroenterol. Hepatol. Bed Bench 2011, 4, 159– 163382https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cjjsVKntg%253D%253D&md5=a3496c2366660a693ad92ef59d6d206cPsychological disorders in patients with chronic constipationHosseinzadeh Sahar Tahbaz; Poorsaadati Sara; Radkani Babak; Forootan MojganGastroenterology and hepatology from bed to bench (2011), 4 (3), 159-63 ISSN:2008-2258.AIM: The aim of present study was to screen two categories of psychiatric disorders in chronic functional constipation. BACKGROUND: It has been established that the prevalence of mood and anxiety disorders among patients with functional gastrointestinal disorders is higher than in the general population. PATIENTS AND METHODS: Fifty four constipated patients were recruited from patients referred to the motility disorder department of Research Center for Gastroentrology and Liver Diseases, and screened for psychiatric disorders using HADS (Hospital Anxiety and Depression Scale) and MINI (Mini International Neuropsychiatric Interview). RESULTS: The results showed a relatively high prevalence of anxiety and depression both in HADS (33.3% and 22.2% respectively) and MINI (33.3% and 31.5% respectively). CONCLUSION: Based on our results the prevalence of mood and anxiety disorders in constipated patients is much higher than general population and in order to reduce health care costs for constipated patients, we need to have an intervention program for comorbid psychological dysfunctions which affect the course of gastrointestinal disorders.
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383Duan, S.; Liu, L.; Li, G.; Wang, J.; Hu, Y.; Zhang, W.; Tan, Z.; Jia, Z.; Zhang, L.; von Deneen, K. M. Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation. Front. Neurosci. 2021, 15, 628880, DOI: 10.3389/fnins.2021.628880383https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sfjt1Wrsg%253D%253D&md5=5031575d2818003f70e06bc5c1d2b1f8Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional ConstipationDuan Shijun; Cui Guangbin; Liu Lei; Li Guanya; Wang Jia; Hu Yang; Zhang Wenchao; Tan Zongxin; Jia Zhenzhen; Zhang Lei; von Deneen Karen M; Zhang Yi; Nie YongzhanFrontiers in neuroscience (2021), 15 (), 628880 ISSN:1662-4548.Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)-rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex-rACC, PreCen-aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN-SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.
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384Hu, C.; Liu, L.; Liu, L.; Zhang, J.; Hu, Y.; Zhang, W.; Ding, Y.; Wang, Y.; Zhang, Z.; von Deneen, K. M. Cortical morphometry alterations in brain regions involved in emotional, motor-control and self-referential processing in patients with functional constipation. Brain Imaging Behav. 2020, 14, 1899– 1907, DOI: 10.1007/s11682-019-00133-4384https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M3os1Oksw%253D%253D&md5=d8f15908d489fde802726cfec4cde8aeCortical morphometry alterations in brain regions involved in emotional, motor-control and self-referential processing in patients with functional constipationHu Chunxin; Liu Li; Liu Lei; Hu Yang; Zhang Wenchao; Ding Yueyan; Wang Yuanyuan; Zhang Zhida; von Deneen Karen M; Zhang Yi; Zhang Junwang; Nie Yongzhan; Qian Long; Wang Huaning; Duan Shijun; Cui Guangbin; Wang FanBrain imaging and behavior (2020), 14 (5), 1899-1907 ISSN:.Functional constipation (FC) is a common functional gastrointestinal disorder (FGID). Neuroimaging studies on patients with FC showed brain functional abnormalities in regions involved in emotional process modulation, somatic and sensory processing and motor control. Brain structural imaging studies in patients with FGID have also shown disease-related alterations in cortical morphometry, but whether and how FC affects brain structure remains unclear. Structural Magnetic Resonance Imaging and surface-based morphometry analysis were used to investigate the impact of FC on cortical morphometry in 29 patients with FC and 29 healthy controls (HC). Results showed that patients with FC compared to HC had significantly decreased cortical thickness in the left middle frontal gyrus (MFG), dorsomedial (DMPFC) and ventromedial prefrontal gyrus (VMPFC), right dorsal anterior cingulate cortex (dACC), left orbitofrontal cortex (OFC), posterior cingulate cortex (PCC)/precuneus, middle temporal gyrus (MTG), and supplementary motor area (SMA) (P < 0.01). Correlation analysis showed that sensation of incomplete evacuation was negatively correlated with cortical thickness in the SMA (P < 0.0001). In addition, patients with FC also had decreased cortical volume than HC in the MTG, precentral gyrus (PreCen) and precuneus/cuneus (P < 0.01), as well as decreased cortical surface area in the PreCen (P < 0.01). No correlation was found between cortical volume/surface area and behavioral measures. These findings suggest that patients with FC are associated with cortical morphometric abnormalities in brain regions implicated in somatic/motor-control, emotional processing and self-referential processing.
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385Jin, Q.; Duan, S.; Li, G.; Sun, L.; Hu, Y.; Hu, C.; Zhao, J.; von Deneen, K. M.; Qian, L.; Wang, H. Sex-related differences in resting-state brain activity and connectivity in the orbital frontal cortex and insula in patients with functional constipation. Neurogastroenterol. Motil. 2019, 31, e13566, DOI: 10.1111/nmo.13566There is no corresponding record for this reference.
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386Li, G.; Zhang, W.; Hu, Y.; Wang, J.; Li, J.; Jia, Z.; Zhang, L.; Sun, L.; von Deneen, K. M.; Duan, S. Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders. Psychosom. Med. 2021, 83, 707– 714, DOI: 10.1097/PSY.0000000000000958386https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c7ntFKquw%253D%253D&md5=9f73f08c89e19547885135febd13147fDistinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive DisordersLi Guanya; Zhang Wenchao; Hu Yang; Wang Jia; Li Jingyuan; Jia Zhenzhen; Zhang Lei; Sun Lijuan; von Deneen Karen M; Duan Shijun; Wang Huaning; Wu Kaichun; Fan Daiming; Cui Guangbin; Zhang Yi; Nie YongzhanPsychosomatic medicine (2021), 83 (7), 707-714 ISSN:.OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.
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387Liu, L.; Hu, C.; Hu, Y.; Zhang, W.; Zhang, Z.; Ding, Y.; Wang, Y.; von Deneen, K. M.; Sun, L.; Wang, H. Abnormalities in the thalamo-cortical network in patients with functional constipation. Brain Imaging Behav. 2021, 15, 630– 642, DOI: 10.1007/s11682-020-00273-y387https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38znsFyjsA%253D%253D&md5=87efccc9c08eb909fc5c6fff9a196d48Abnormalities in the thalamo-cortical network in patients with functional constipationLiu Lei; Hu Chunxin; Hu Yang; Zhang Wenchao; Zhang Zhida; Ding Yueyan; Wang Yuanyuan; von Deneen Karen M; Liu Jixin; Zhang Yi; Sun Lijuan; Nie Yongzhan; Wang Huaning; Duan Shijun; Cui Guangbin; Mao Kuanrong; Wang FanBrain imaging and behavior (2021), 15 (2), 630-642 ISSN:.Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.
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388Peihong, M.; Tao, Y.; Zhaoxuan, H.; Sha, Y.; Li, C.; Kunnan, X.; Jingwen, C.; Likai, H.; Yuke, T.; Yuyi, G. Alterations of White Matter Network Properties in Patients With Functional Constipation. Front. Neurol. 2021, 12, 627130, DOI: 10.3389/fneur.2021.627130388https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3sfps1Oiug%253D%253D&md5=ddda1505946ed80f6542de1d87f20c55Alterations of White Matter Network Properties in Patients With Functional ConstipationPeihong Ma; Tao Yin; Zhaoxuan He; Sha Yang; Li Chen; Kunnan Xie; Jingwen Chen; Likai Hou; Yuke Teng; Yuyi Guo; Fumin Wang; Zilei Tian; Ruirui Sun; Fang Zeng; Peihong Ma; Tao Yin; Zhaoxuan He; Sha Yang; Li Chen; Kunnan Xie; Jingwen Chen; Likai Hou; Yuke Teng; Yuyi Guo; Fumin Wang; Zilei Tian; Ruirui Sun; Fang ZengFrontiers in neurology (2021), 12 (), 627130 ISSN:1664-2295.Background: The abnormalities in brain function and structure of patients with functional constipation (FC) have been identified using multiple neuroimaging studies and have confirmed the abnormal processing of visceral sensation at the level of the central nervous system (CNS) as an important reason for FC. As an important basis for central information transfer, the role of the white matter (WM) networks in the pathophysiology of FC has not been investigated. This study aimed to explore the topological organization of WM networks in patients with FC and its correlation with clinical variables. Methods and Analysis: In this study, 70 patients with FC and 45 age- and gender-matched healthy subjects (HS) were recruited. Diffusion tensor imaging (DTI) data and clinical variables were acquired from each participant. WM networks were constructed using the deterministic fiber tracking approach, and the global and nodal properties of the WM networks were compared using graph theory analysis between patients with FC and HS. The relationship between the representative nodal characteristics-nodal betweenness and clinical parameters was assessed using partial correlation analysis. Results: Patients with FC showed increased nodal characteristics in the left superior frontal gyrus (orbital part), right middle frontal gyrus (orbital part), and right anterior cingulate and paracingulate (P < 0.05, corrected for false discovery rate) and decreased nodal characteristics in the left caudate and left thalamus (P < 0.05, corrected for false discovery rate) compared with HS. The duration of FC was negatively correlated with the nodal betweenness of the left thalamus (r = -0.354, P = 0.04, corrected for false discovery rate). Conclusion: The results indicated the alternations in WM networks of patients with FC and suggested the abnormal visceral sensation processing in the CNS from the perspective of large-scale brain WM network.
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389Zhu, Q.; Cai, W.; Zheng, J.; Li, G.; Meng, Q.; Liu, Q.; Zhao, J.; von Deneen, K. M.; Wang, Y.; Cui, G. Distinct resting-state brain activity in patients with functional constipation. Neurosci. Lett. 2016, 632, 141– 146, DOI: 10.1016/j.neulet.2016.08.042389https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsV2rtrrO&md5=c5385b3f0966e0a80f804c6efc92e11dDistinct resting-state brain activity in patients with functional constipationZhu, Qiang; Cai, Weiwei; Zheng, Jianyong; Li, Guanya; Meng, Qianqian; Liu, Qiaoyun; Zhao, Jizheng; von Deneen, Karen M.; Wang, Yuanyuan; Cui, Guangbin; Duan, Shijun; Han, Yu; Wang, Huaning; Tian, Jie; Zhang, Yi; Nie, YongzhanNeuroscience Letters (2016), 632 (), 141-146CODEN: NELED5; ISSN:0304-3940. (Elsevier Ireland Ltd.)Functional constipation (FC) is a common functional gastrointestinal disorder (FGID) with a higher prevalence in clin. practice. The primary brain regions involved in emotional arousal regulation, somatic, sensory and motor control processing have been identified with neuroimaging in FGID. It remains unclear how these factors interact to influence the baseline brain activity of patients with FC. In the current study, we combined resting-state fMRI (RS-fMRI) with Granger causality anal. (GCA) to investigate the causal interactions of the brain areas in 14 patients with FC and in 26 healthy controls (HC). Our data showed significant differences in baseline brain activities in a no. of major brain regions implicated in emotional process modulation (i.e. dorsal anterior cingulate cortex-dACC, anterior insula-aINS, orbitofrontal cortex-OFC, hippocampus-HIPP), somatic and sensory processing, and motor control (i.e., supplementary motor area-SMA, precentral gyrus-PreCen) (P < 0.05, FDR correction). The GCA results revealed stronger effective connectivity from the OFC and dACC, which are regions involved with emotional regulation, propel limbic regions at the aINS and HIPP to induce abnormal emotional processing regulating visceral responses; and weaker effective connectivity from the SMA and PreCen, which are regions involved with somatic, sensory and motor control, propel the aINS and HIPP, suggesting abnormalities of sensory and behavioral responses. Such information of basal level functional abnormalities expands our current understanding of neural mechanisms underlying functional constipation.
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390Mayer, E. A. Gut feelings: the emerging biology of gut–brain communication. Nat. Rev. Neurosci. 2011, 12, 453– 466, DOI: 10.1038/nrn3071390https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXoslynsLY%253D&md5=7d6d83bdc389070ef5902435a335ead0Gut feelings: the emerging biology of gut-brain communicationMayer, Emeran A.Nature Reviews Neuroscience (2011), 12 (8), 453-466CODEN: NRNAAN; ISSN:1471-003X. (Nature Publishing Group)A review. The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language. Recent neurobiol. insights into this gut-brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making. Moreover, disturbances of this system have been implicated in a wide range of disorders, including functional and inflammatory gastrointestinal disorders, obesity and eating disorders.
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391Rubio, A.; Van Oudenhove, L.; Pellissier, S.; Ly, H. G.; Dupont, P.; Lafaye de Micheaux, H.; Tack, J.; Dantzer, C.; Delon-Martin, C.; Bonaz, B. Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers. NeuroImage 2015, 107, 10– 22, DOI: 10.1016/j.neuroimage.2014.11.043391https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MzlsFehtw%253D%253D&md5=23c620d64a51b6bcdb828c2f8bda6ef4Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteersRubio Amandine; Van Oudenhove Lukas; Pellissier Sonia; Ly Huynh Giao; Tack Jan; Dupont Patrick; Lafaye de Micheaux Hugo; Delon-Martin Chantal; Dantzer Cecile; Bonaz BrunoNeuroImage (2015), 107 (), 10-22 ISSN:.The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases.
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392Molina-Torres, G.; Rodriguez-Arrastia, M.; Roman, P.; Sanchez-Labraca, N.; Cardona, D. Stress and the gut microbiota-brain axis. Behav. Pharmacol. 2019, 30, 187– 200, DOI: 10.1097/FBP.0000000000000478392https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cbhsFaitg%253D%253D&md5=8be6a31e1f4533b89310b431ad7c6af7Stress and the gut microbiota-brain axisMolina-Torres Guadalupe; Rodriguez-Arrastia Miguel; Roman Pablo; Sanchez-Labraca Nuria; Cardona DianaBehavioural pharmacology (2019), 30 (2 and 3-Spec Issue), 187-200 ISSN:.Stress is a nonspecific response of the body to any demand imposed upon it, disrupting the body homoeostasis and manifested with symptoms such as anxiety, depression or even headache. These responses are quite frequent in the present competitive world. The aim of this review is to explore the effect of stress on gut microbiota. First, we summarize evidence of where the microbiota composition has changed as a response to a stressful situation, and thereby the effect of the stress response. Likewise, we review different interventions that can modulate microbiota and could modulate the stress according to the underlying mechanisms whereby the gut-brain axis influences stress. Finally, we review both preclinical and clinical studies that provide evidence of the effect of gut modulation on stress. In conclusion, the influence of stress on gut microbiota and gut microbiota on stress modulation is clear for different stressors, but although the preclinical evidence is so extensive, the clinical evidence is more limited. A better understanding of the mechanism underlying stress modulation through the microbiota may open new avenues for the design of therapeutics that could boost the pursued clinical benefits. These new designs should not only focus on stress but also on stress-related disorders such as anxiety and depression, in both healthy individuals and different populations.
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393Vanuytsel, T.; van Wanrooy, S.; Vanheel, H.; Vanormelingen, C.; Verschueren, S.; Houben, E.; Salim Rasoel, S.; Tóth, J.; Holvoet, L.; Farré, R. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 2014, 63, 1293– 1299, DOI: 10.1136/gutjnl-2013-305690393https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFGhurrM&md5=0f2a785b5222b819e54ed20b2fe414f5Psychological stress and corticotropin-releasing hormone increase intestinal perrneability in humans by a mast cell-dependent mechanismVanuytsel, Tiro; van Wanrooy, Sander; Vanheel, Hanne; Vanormelingen, Christophe; Verschueren, Sofie; Houben, Eis; Rasoel, Shadea Salim; Toth, Joran; Holvoet, Lieselot; Farre, Ricard; Van Oudenhove, Lukas; Boeckxstaens, Guy; Verbeke, Kristin; Tack, JanGut (2014), 63 (8), 1293-1299CODEN: GUTTAK; ISSN:0017-5749. (BMJ Publishing Group)Objective Intestinal permeability and psychol. stress have been implicated in the pathophysiol. of IBD and IBS. Studies in animals suggest that stress increases permeability via corticotropin-releasing hormone (CRH)-mediated mast cell activation. Our aim was to investigate the effect of stress on intestinal permeability in humans and its underlying mechanisms. Design Small intestinal permeability was quantified by a 2 h lactulose-mannitol urinary excretion test. In a first study, 23 healthy volunteers were subjected to four different conditions: control; indomethacin; public speech and anticipation of electroshocks. In a second study, five test conditions were investigated in 13 volunteers: control; after pretreatment with disodium cromoglycate (DSCG); administration of CRH; DSCG+CRH and DSCG +public speech. Results Indomethacin, as a pos. comparator (0.071±0.040 vs 0.030±0.022; p<0.0001), and public speech (0.059±0.040; p<0.01), but not the shock protocol increased intestinal permeability. Similarly, salivary cortisol was only increased after public speech. Subgroup anal. demonstrated that the effect of public speech on permeability was only present in subjects with a significant elevation of cortisol. CRH increased the lactulose-mannitol ratio (0.042±0.021 vs 0.028±0.009; p=0.02), which was inhibited by the mast cell stabilizer DSCG. Finally, intestinal permeability was unaltered by public speech with DSCG pretreatment. Conclusions Acute psychol. stress increases small intestinal permeability in humans. Peripheral CRH reproduces the effect of stress and DSCG blocks the effect of both stress and CRH, suggesting the involvement of mast cells. These findings provide new insight into the complex interplay between the central nervous system and GI function in man.
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394Yarandi, S. S.; Peterson, D. A.; Treisman, G. J.; Moran, T. H.; Pasricha, P. J. Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases. J. Neurogastroenterol. Motil. 2016, 22, 201– 212, DOI: 10.5056/jnm15146394https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28flslyntg%253D%253D&md5=a8f9435630fc3c88946e23865acf98e3Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and DiseasesYarandi Shadi S; Pasricha Pankaj J; Peterson Daniel A; Treisman Glen J; Moran Timothy HJournal of neurogastroenterology and motility (2016), 22 (2), 201-12 ISSN:2093-0879.Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.
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395Kelly, J. R.; Kennedy, P. J.; Cryan, J. F.; Dinan, T. G.; Clarke, G.; Hyland, N. P. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 2015, 9, 392, DOI: 10.3389/fncel.2015.00392395https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXlvVClt78%253D&md5=5ef019ed88138c8045ffb0f1df040cfdBreaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disordersKelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.Frontiers in Cellular Neuroscience (2015), 9 (), 392/1-392/20CODEN: FCNRAH; ISSN:1662-5102. (Frontiers Media S.A.)The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiol. of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a crit. node within the brain-gut axis. Mounting preclin. evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low grade inflammation obsd. in disorders such as depression and the gut microbiome plays a crit. role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clin. and preclin. evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.
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396Tannock, G. W.; Savage, D. C. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect. Immun. 1974, 9, 591– 598, DOI: 10.1128/iai.9.3.591-598.1974396https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaE2c7itFKhug%253D%253D&md5=37c815abc5ba5dfea79f92d3e98a52d3Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tractTannock G W; Savage D CInfection and immunity (1974), 9 (3), 591-8 ISSN:0019-9567.Aerobic and anaerobic cultural techniques and histological methods were used in a study of the effects of environmental and dietary stress on the indigenous microbiota of the gastrointestinal tract of mice. Mice previously inoculated with Salmonella typhimurium were examined in a similar manner. Three strains of mice (CD-1, Ha/ICr, and C57BL) were used. Control animals previously inoculated with S. typhimurium had low population levels of Salmonella bacteria in the small and large bowel. Mice previously inoculated with Salmonella and then deprived of food, water, and bedding for 48 h harbored high population levels of these bacteria in their small and large bowels. Coliforms increased in numbers in the large bowel of stressed mice inoculated with Salmonella and in the jejunum-ileum and cecum of stressed mice not previously inoculated with Salmonella. Control mice had high population levels of lactobacilli inhabiting the keratinized squamous epithelium of the stomach. Stressed mice showed dramatic reductions in these populations of lactobacilli. Populations of fusiform-shaped bacteria associated with the mucosal epithelium of the cecum and colon in control mice were reduced in stressed mice as determined by microscope examination of histological sections. Total anaerobic counts were similar, however, in both stressed and control animals. Environmental and dietary stress markedly alter the gastrointestinal microbiota in mice. Therefore, such stressful conditions profoundly affect the factors that regulate the localization and population levels of microorganisms in the stomach and intestines.
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397Yang, H.; Zhao, X.; Tang, S.; Huang, H.; Zhao, X.; Ning, Z.; Fu, X.; Zhang, C. Probiotics reduce psychological stress in patients before laryngeal cancer surgery. Asia Pac. J. Clin. Oncol. 2016, 12, e92– 96, DOI: 10.1111/ajco.12120There is no corresponding record for this reference.
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398Karl, J. P.; Margolis, L. M.; Madslien, E. H.; Murphy, N. E.; Castellani, J. W.; Gundersen, Y.; Hoke, A. V.; Levangie, M. W.; Kumar, R.; Chakraborty, N. Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress. Am. J. Physiol. Gastrointest. Liver Physiol. 2017, 312, G559– g571, DOI: 10.1152/ajpgi.00066.2017There is no corresponding record for this reference.
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399Kato-Kataoka, A.; Nishida, K.; Takada, M.; Kawai, M.; Kikuchi-Hayakawa, H.; Suda, K.; Ishikawa, H.; Gondo, Y.; Shimizu, K.; Matsuki, T. Fermented Milk Containing Lactobacillus casei Strain Shirota Preserves the Diversity of the Gut Microbiota and Relieves Abdominal Dysfunction in Healthy Medical Students Exposed to Academic Stress. Appl. Environ. Microbiol. 2016, 82, 3649– 3658, DOI: 10.1128/AEM.04134-15399https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVykur3P&md5=0b33c7e6ab05b00969fcbec2f69f0696Fermented milk containing Lactobacillus casei strain shirota preserves the diversity of the gut microbiota and relieves abdominal dysfunction in healthy medical students exposed to academic stressKato-Kataoka, Akito; Nishida, Kensei; Takada, Mai; Kawai, Mitsuhisa; Kikuchi-Hayakawa, Hiroko; Suda, Kazunori; Ishikawa, Hiroshi; Gondo, Yusuke; Shimizu, Kensuke; Matsuki, Takahiro; Kushiro, Akira; Hoshi, Ryoutaro; Watanabe, Osamu; Igarashi, Tomoki; Miyazaki, Kouji; Kuwano, Yuki; Rokutan, KazuhitoApplied and Environmental Microbiology (2016), 82 (12), 3649-3658CODEN: AEMIDF; ISSN:1098-5336. (American Society for Microbiology)Stress-induced abdominal dysfunction is an attractive target for probiotics. To investigate the effects of the probiotic Lactobacillus casei strain Shirota on abdominal dysfunction, a double-blind, placebo-controlled trial was conducted with healthy medical students undertaking an authorized nationwide examn. for academic advancement. For 8 wk, until the day before the examn., 23 and 24 subjects consumed an L. casei strain Shirota-fermented milk and a placebo milk daily, resp. In addn. to assessments of abdominal symptoms, psychophys. state, and salivary stress markers, gene expression changes in peripheral blood leukocytes and compn. of the gut microbiota were analyzed using DNA microarray anal. and 16S rRNA gene amplicon sequence anal., resp., before and after the intervention. Stress-induced increases in a visual analog scale measuring feelings of stress, the total score of abdominal dysfunction, and the no. of genes with changes in expression of more than 2-fold in leukocytes were significantly suppressed in the L. casei strain Shirota group compared with those in the placebo group. A significant increase in salivary cortisol levels before the examn. was obsd. only in the placebo group. The administration of L. casei strain Shirota, but not placebo, significantly reduced gastrointestinal symptoms. Moreover, 16S rRNA gene amplicon sequencing demonstrated that the L. casei strain Shirota group had significantly higher nos. of species, a marker of the alpha-diversity index, in their gut microbiota and a significantly lower percentage of Bacteroidaceae than the placebo group. Our findings indicate that the daily consumption of probiotics, such as L. casei strain Shirota, preserves the diversity of the gut microbiota and may relieve stress-assocd. responses of abdominal dysfunction in healthy subjects exposed to stressful situations.
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400Takada, M.; Nishida, K.; Kataoka-Kato, A.; Gondo, Y.; Ishikawa, H.; Suda, K.; Kawai, M.; Hoshi, R.; Watanabe, O.; Igarashi, T. Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal models. Neurogastroenterol. Motil. 2016, 28, 1027– 1036, DOI: 10.1111/nmo.12804400https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtVCisr3K&md5=ad973ade1b9aa11673f6276360a96c43Probiotic Lactobacillus casei strain Shirota relieves stress-associated symptoms by modulating the gut-brain interaction in human and animal modelsTakada, M.; Nishida, K.; Kataoka-Kato, A.; Gondo, Y.; Ishikawa, H.; Suda, K.; Kawai, M.; Hoshi, R.; Watanabe, O.; Igarashi, T.; Kuwano, Y.; Miyazaki, K.; Rokutan, K.Neurogastroenterology & Motility (2016), 28 (7), 1027-1036CODEN: NMOTEK; ISSN:1350-1925. (Wiley-Blackwell)Background : This study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut-brain interactions under stressful conditions. Methods : Three double-blind, placebo-controlled trials were conducted to examine the effects of LcS on psychol. and physiol. stress responses in healthy medical students under academic examn. stress. Subjects received LcS-fermented milk or placebo daily for 8 wk prior to taking a national standardized examn. Subjective anxiety scores, salivary cortisol levels, and the presence of phys. symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 wk, then submitted to water avoidance stress (WAS). Plasma corticosterone concn. and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiol. study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane-anesthetized rats. Key Results : Academic stress-induced increases in salivary cortisol levels and the incidence rate of phys. symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS-induced increases in plasma corticosterone were significantly suppressed, and the no. of CRF-expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose-dependent manner. Conclusions & Inferences : These findings suggest that LcS may prevent hypersecretion of cortisol and phys. symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.
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401Zijlmans, M. A.; Korpela, K.; Riksen-Walraven, J. M.; de Vos, W. M.; de Weerth, C. Maternal prenatal stress is associated with the infant intestinal microbiota. Psychoneuroendocrinology 2015, 53, 233– 245, DOI: 10.1016/j.psyneuen.2015.01.006401https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MrhtlSntw%253D%253D&md5=7a2cb4bf808aeb6c412cfe6731cc83c5Maternal prenatal stress is associated with the infant intestinal microbiotaZijlmans Maartje A C; de Weerth Carolina; Korpela Katri; Riksen-Walraven J Marianne; de Vos Willem MPsychoneuroendocrinology (2015), 53 (), 233-45 ISSN:.Maternal prenatal stress has been often associated with infant physical development and health, as well as psychological functioning and behavior. However, the mechanisms underlying these relations remain elusive. The goal of the present study was to prospectively investigate the development of the intestinal microbiota as a potential pathway linking maternal prenatal stress and infant health. The development of the infant intestinal microbiota was followed over the first 110 days after birth in a healthy cohort of 56 vaginally born Dutch infants. Additionally, the relation between infant intestinal microbiota and gastrointestinal and allergic symptoms was examined. Results showed that maternal prenatal stress, i.e., either reported stress or elevated basal maternal salivary cortisol concentrations or both, was strongly and persistently associated with the infants' microbiota composition as determined by a phylogenetic microarray. Infants of mothers with high cumulative stress (i.e., high reported stress and high cortisol concentrations) during pregnancy had significantly higher relative abundances of Proteobacterial groups known to contain pathogens (related to Escherichia, Serratia, and Enterobacter), and lower relative abundances of lactic acid bacteria (i.e., Lactobacillus, Lactoccus, Aerococcus) and Bifidobacteria, altogether characteristics of a potentially increased level of inflammation. Furthermore, this aberrant colonization pattern was related to more maternally reported infant gastrointestinal symptoms and allergic reactions. In conclusion, clear links were found between maternal prenatal stress and the infant intestinal microbiota and health. Although causality cannot be concluded, the results suggest a possible mechanism by which maternal prenatal stress influences the offspring development. These results suggest a potential for bacterial interventions to enhance offspring health and development in pregnant women with stress.
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402Naseribafrouei, A.; Hestad, K.; Avershina, E.; Sekelja, M.; Linlo̷kken, A.; Wilson, R.; Rudi, K. Correlation between the human fecal microbiota and depression. Neurogastroenterol. Motil. 2014, 26, 1155– 1162, DOI: 10.1111/nmo.12378402https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cjotlansg%253D%253D&md5=8617b1502f3d8c8a26fc5e9b81b61427Correlation between the human fecal microbiota and depressionNaseribafrouei A; Hestad K; Avershina E; Sekelja M; Linlokken A; Wilson R; Rudi KNeurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (2014), 26 (8), 1155-62 ISSN:.BACKGROUND: Depression is a chronic syndrome with a pathogenesis linked to various genetic, biological, and environmental factors. Several links between gut microbiota and depression have been established in animal models. In humans, however, few correlations have yet been demonstrated. The aim of our work was therefore to identify potential correlations between human fecal microbiota (as a proxy for gut microbiota) and depression. METHODS: We analyzed fecal samples from 55 people, 37 patients, and 18 non-depressed controls. Our analyses were based on data generated by Illumina deep sequencing of 16S rRNA gene amplicons. KEY RESULTS: We found several correlations between depression and fecal microbiota. The correlations, however, showed opposite directions even for closely related Operational Taxonomic Units (OTU's), but were still associated with certain higher order phylogroups. The order Bacteroidales showed an overrepresentation (p = 0.05), while the family Lachnospiraceae showed an underrepresentation (p = 0.02) of OTU's associated with depression. At low taxonomic levels, there was one clade consisting of five OTU's within the genus Oscillibacter, and one clade within Alistipes (consisting of four OTU's) that showed a significant association with depression (p = 0.03 and 0.01, respectively). CONCLUSIONS & INFERENCES: The Oscillibacter type strain has valeric acid as its main metabolic end product, a homolog of neurotransmitter GABA, while Alistipes has previously been shown to be associated with induced stress in mice. In conclusion, the taxonomic correlations detected here may therefore correspond to mechanistic models.
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403Jiang, H.; Ling, Z.; Zhang, Y.; Mao, H.; Ma, Z.; Yin, Y.; Wang, W.; Tang, W.; Tan, Z.; Shi, J. Altered fecal microbiota composition in patients with major depressive disorder. Brain. Behav. Immun. 2015, 48, 186– 194, DOI: 10.1016/j.bbi.2015.03.016403https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MjkvVOrsQ%253D%253D&md5=efccc79e76ef72ca53b2a01088a42434Altered fecal microbiota composition in patients with major depressive disorderJiang Haiyin; Ling Zongxin; Zhang Yonghua; Mao Hongjin; Yin Yan; Tang Wenxin; Tan Zhonglin; Shi Jianfei; Ma Zhanping; Wang Weihong; Li Lanjuan; Ruan BingBrain, behavior, and immunity (2015), 48 (), 186-94 ISSN:.Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.
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404Tillisch, K.; Mayer, E. A.; Gupta, A.; Gill, Z.; Brazeilles, R.; Le Nevé, B.; van Hylckama Vlieg, J. E. T.; Guyonnet, D.; Derrien, M.; Labus, J. S. Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women. Psychosom. Med. 2017, 79, 905– 913, DOI: 10.1097/PSY.0000000000000493404https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cjjtVSjug%253D%253D&md5=cf95fddf62483d46ff0bb43092b984e5Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy WomenTillisch Kirsten; Mayer Emeran A; Gupta Arpana; Gill Zafar; Brazeilles Remi; Le Neve Boris; van Hylckama Vlieg Johan E T; Guyonnet Denis; Derrien Muriel; Labus Jennifer SPsychosomatic medicine (2017), 79 (8), 905-913 ISSN:.OBJECTIVE: Brain-gut-microbiota interactions may play an important role in human health and behavior. Although rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive, and social behaviors, there is little translational human evidence to date. In this study, we identify brain and behavioral characteristics of healthy women clustered by gut microbiota profiles. METHODS: Forty women supplied fecal samples for 16S rRNA profiling. Microbial clusters were identified using Partitioning Around Medoids. Functional magnetic resonance imaging was acquired. Microbiota-based group differences were analyzed in response to affective images. Structural and diffusion tensor imaging provided gray matter metrics (volume, cortical thickness, mean curvature, surface area) as well as fiber density between regions. A sparse Partial Least Square-Discrimination Analysis was applied to discriminate microbiota clusters using white and gray matter metrics. RESULTS: Two bacterial genus-based clusters were identified, one with greater Bacteroides abundance (n = 33) and one with greater Prevotella abundance (n = 7). The Prevotella group showed less hippocampal activity viewing negative valences images. White and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2%, respectively. The Prevotella cluster was associated with differences in emotional, attentional, and sensory processing regions. For gray matter, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and the hippocampus. CONCLUSIONS: These results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain, and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior.
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405Pfau, M. L.; Russo, S. J. Peripheral and Central Mechanisms of Stress Resilience. Neurobiol Stress 2015, 1, 66– 79, DOI: 10.1016/j.ynstr.2014.09.004405https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2srjtVCitw%253D%253D&md5=350802b947683c68f598f7d951b74e0cPeripheral and Central Mechanisms of Stress ResiliencePfau Madeline L; Russo Scott JNeurobiology of stress (2015), 1 (), 66-79 ISSN:2352-2895.Viable new treatments for depression and anxiety have been slow to emerge, likely owing to the complex and incompletely understood etiology of these disorders. A budding area of research with great therapeutic promise involves the study of resilience, the adaptive maintenance of normal physiology and behavior despite exposure to marked psychological stress. This phenomenon, documented in both humans and animal models, involves coordinated biological mechanisms in numerous bodily systems, both peripheral and central. In this review, we provide an overview of resilience mechanisms throughout the body, discussing current research in animal models investigating the roles of the neuroendocrine, immune, and central nervous systems in behavioral resilience to stress.
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406Franklin, T. B.; Saab, B. J.; Mansuy, I. M. Neural mechanisms of stress resilience and vulnerability. Neuron 2012, 75, 747– 761, DOI: 10.1016/j.neuron.2012.08.016406https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlSkt7jJ&md5=04d0c42fc745a5e64ed2ab8b129503b4Neural Mechanisms of Stress Resilience and VulnerabilityFranklin, Tamara B.; Saab, Bechara J.; Mansuy, Isabelle M.Neuron (2012), 75 (5), 747-761CODEN: NERNET; ISSN:0896-6273. (Cell Press)Exposure to stressful events can be differently perceived by individuals and can have persistent sequelae depending on the level of stress resilience or vulnerability of each person. The neural processes that underlie such clin. and socially important differences reside in the anatomical, functional, and mol. connectivity of the brain. Recent work has provided novel insight into some of the involved biol. mechanisms that promises to help prevent and treat stress-related disorders. In this review, we focus on causal and mechanistic evidence implicating altered functions and connectivity of the neuroendocrine system, and of hippocampal, cortical, reward, and serotonergic circuits in the establishment and the maintenance of stress resilience and vulnerability. We also touch upon recent findings suggesting a role for epigenetic mechanisms and neurogenesis in these processes and briefly discuss promising avenues of future investigation.
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407Bear, T.; Dalziel, J.; Coad, J.; Roy, N.; Butts, C.; Gopal, P. The Microbiome-Gut-Brain Axis and Resilience to Developing Anxiety or Depression under Stress. Microorganisms 2021, 9, 723, DOI: 10.3390/microorganisms9040723407https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvFygsbnP&md5=ae3d72141ae28d7267f5b0f9ffec9eecThe microbiome-gut-brain axis and resilience to developing anxiety or depression under stressBear, Tracey; Dalziel, Julie; Coad, Jane; Roy, Nicole; Butts, Christine; Gopal, PramodMicroorganisms (2021), 9 (4), 723CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)Episodes of depression and anxiety commonly follow the experience of stress, however not everyone who experiences stress develops a mood disorder. Individuals who are able to experience stress without a neg. emotional effect are considered stress resilient. Stress-resilience (and its counterpart stress-susceptibility) are influenced by several psychol. and biol. factors, including the microbiome-gut-brain axis. Emerging research shows that the gut microbiota can influence mood, and that stress is an important variable in this relationship. Stress alters the gut microbiota and plausibly this could contribute to stress-related changes in mood. Most of the reported research has been conducted using animal models and demonstrates a relationship between gut microbiome and mood. The translational evidence from human clin. studies however is rather limited. In this review we examine the microbiome-gut-brain axis research in relation to stress resilience.
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408Li, L. F.; Zou, H. W.; Song, B. L.; Wang, Y.; Jiang, Y.; Li, Z. L.; Niu, Q. H.; Liu, Y. J. Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat Stress. Neuroendocrinology 2023, 113, 563, DOI: 10.1159/000528876408https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXosFGks7s%253D&md5=67aff20b688aeffcb4be5727d0c10449Increased Lactobacillus Abundance Contributes to Stress Resilience in Mice Exposed to Chronic Social Defeat StressLi, Lai-Fu; Zou, Hua-Wei; Song, Bai-Lin; Wang, Yan; Jiang, Yi; Li, Zi-Lin; Niu, Qiu-Hong; Liu, Ying-JuanNeuroendocrinology (2023), 113 (5), 563-576CODEN: NUNDAJ; ISSN:0028-3835. (S. Karger AG)Introduction: Accumulating evidence indicates that abnormalities in the compn. of gastrointestinal (GI) microbiota play a vital role in stress-related disorders. Both human beings and animals perceive stressful events differently, i.e., resilience or susceptibility. However, the role of GI microbiota in stress resilience/susceptibility and the underlying mechanisms remain largely unknown. Methods and Results: Sixty male C57BL/6J mice were exposed to 10-day chronic social defeat stress (CSDS), and 28 were found to be resilient to CSDS. We next analyzed microbiota compns. in the cecum using 16S rDNA gene sequencing, which revealed a significant increase in the relative abundance of Lactobacillus at the genus level in the resilient mice. In subsequent expts., we found that oral administration of a strain of Lactobacillus (Lactobacillus murinus) for 2 wk attenuated the increased levels of stress-induced corticosterone and anxiety-like behavior in stress-susceptible mice. The mRNA expression of tryptophan hydroxylase 2 (a rate-limiting enzyme in serotonin [5-HT] synthesis) was also significantly increased in the dorsal raphe nucleus (DR) of stress-susceptible mice. Conclusions: Lactobacillus contributes to stress resilience, and the DR 5-HT system may play an important role during this process. The above results suggest that certain organisms in the GI tract may play an essential role in stress response and be useful in the prevention and treatment of some stress-related psychiatric disorders, such as depression.
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409Dinan, T. G.; Stanton, C.; Cryan, J. F. Psychobiotics: a novel class of psychotropic. Biol. Psychiatry 2013, 74, 720– 726, DOI: 10.1016/j.biopsych.2013.05.001409https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXptFGktLw%253D&md5=ff4777b31cb75114db2df567eaf8ed5fPsychobiotics: A Novel Class of PsychotropicDinan, Timothy G.; Stanton, Catherine; Cryan, John F.Biological Psychiatry (2013), 74 (10), 720-726CODEN: BIPCBF; ISSN:0006-3223. (Elsevier)A review. Here, we define a psychobiotic as a live organism that, when ingested in adequate amts., produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis. Preclin. evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems. So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where pos. benefits have been reported for a no. of organisms including Bifidobacterium infantis. Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such benefits may be related to the anti-inflammatory actions of certain psychobiotics and a capacity to reduce hypothalamic-pituitary-adrenal axis activity. Results from large scale placebo-controlled studies are awaited.
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410Chattu, V. K.; Manzar, M. D.; Kumary, S.; Burman, D.; Spence, D. W.; Pandi-Perumal, S. R. The Global Problem of Insufficient Sleep and Its Serious Public Health Implications. Healthcare 2019, 7, 1, DOI: 10.3390/healthcare7010001There is no corresponding record for this reference.
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411Irwin, C.; McCartney, D.; Desbrow, B.; Khalesi, S. Effects of probiotics and paraprobiotics on subjective and objective sleep metrics: a systematic review and meta-analysis. Eur. J. Clin. Nutr. 2020, 74, 1536– 1549, DOI: 10.1038/s41430-020-0656-x411https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38vpsVymtw%253D%253D&md5=4bf85a14c79b5fa2362c983b78c24c6dEffects of probiotics and paraprobiotics on subjective and objective sleep metrics: a systematic review and meta-analysisIrwin Christopher; Desbrow Ben; Irwin Christopher; McCartney Danielle; Khalesi SamanEuropean journal of clinical nutrition (2020), 74 (11), 1536-1549 ISSN:.Inadequate sleep (i.e., duration and/or quality) is becoming increasingly recognized as a global public health issue. Interaction via the gut-brain axis suggests that modification of the gut microbial environment via supplementation with live microorganisms (probiotics) or nonviable microorganisms/microbial cell fractions (paraprobiotics) may improve sleep health. This systematic review and meta-analysis aimed to clarify the effect of consuming probiotics/paraprobiotics on subjective and objective sleep metrics. Online databases were searched from 1980 to October 2019 for studies involving adults who consumed probiotics or paraprobiotics in controlled trials, during which, changes in subjective and/or objective sleep parameters were examined. A total of 14 studies (20 trials) were included in meta-analysis. Random effects meta-analyses indicated that probiotics/paraprobiotics supplementation significantly reduced Pittsburgh Sleep Quality Index (PSQI) score (i.e., improved sleep quality) relative to baseline (-0.78-points, 95% confidence interval: 0.395-1.166; p < 0.001). No significant effect was found for changes on other subjective sleep scales, nor objective parameters of sleep (efficiency/latency) measured using polysomnography or actigraphy. Subgroup analysis for PSQI data suggested that the magnitude of the effect was greater (although not statistically) in healthy participants than those with a medical condition, when treatment contained a single (rather than multiple) strain of probiotic bacteria, and when the duration of treatment was ≥8 weeks. Probiotics/paraprobiotics supplementation may have some efficacy in improving perceived sleep health, measured using the PSQI. While current evidence does not support a benefit of consuming probiotics/paraprobiotics when measured by other subjective sleep scales, nor objective measures of sleep; more studies using well-controlled, within-subject experimental designs are needed.
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412Smith, R. P.; Easson, C.; Lyle, S. M.; Kapoor, R.; Donnelly, C. P.; Davidson, E. J.; Parikh, E.; Lopez, J. V.; Tartar, J. L. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One 2019, 14, e0222394 DOI: 10.1371/journal.pone.0222394412https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXit1SitbzI&md5=df4265f4dc5ab89d8e8d5ea3aeeaf61dGut microbiome diversity is associated with sleep physiology in humansSmith, Robert P.; Easson, Cole; Lyle, Sarah M.; Kapoor, Ritishka; Donnelly, Chase P.; Davidson, Eileen J.; Parikh, Esha; Lopez, Jose V.; Tartar, Jaime L.PLoS One (2019), 14 (10), e0222394CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that the gut microbiome can influence sleep quality. Previous studies that have examd. sleep deprivation and the human gut microbiome have yielded conflicting results. A recent study found that sleep deprivation leads to changes in gut microbiome compn. while a different study found that sleep deprivation does not lead to changes in gut microbiome. Accordingly, the relationship between sleep physiol. and the gut microbiome remains unclear. To address this uncertainty, we used actigraphy to quantify sleep measures coupled with gut microbiome sampling to det. how the gut microbiome correlates with various measures of sleep physiol. We measured immune system biomarkers and carried out a neurobehavioral assessment as these variables might modify the relationship between sleep and gut microbiome compn. We found that total microbiome diversity was pos. correlated with increased sleep efficiency and total sleep time, and was neg. correlated with wake after sleep onset. We found pos. correlations between total microbiome diversity and interleukin-6, a cytokine previously noted for its effects on sleep. Anal. of microbiome compn. revealed that within phyla richness of Bacteroidetes and Firmicutes were pos. correlated with sleep efficiency, interleukin-6 concns. and abstr. thinking. Finally, we found that several taxa (Lachnospiraceae, Corynebacterium, and Blautia) were neg. correlated with sleep measures. Our findings initiate linkages between gut microbiome compn., sleep physiol., the immune system and cognition. They may lead to mechanisms to improve sleep through the manipulation of the gut microbiome.
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413Benedict, C.; Vogel, H.; Jonas, W.; Woting, A.; Blaut, M.; Schürmann, A.; Cedernaes, J. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Molecular Metabolism 2016, 5, 1175– 1186, DOI: 10.1016/j.molmet.2016.10.003413https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslKksbnO&md5=8574818ba82e517a8811c2d448e71218Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individualsBenedict, Christian; Vogel, Heike; Jonas, Wenke; Woting, Anni; Blaut, Michael; Schurmann, Annette; Cedernaes, JonathanMolecular Metabolism (2016), 5 (12), 1175-1186CODEN: MMOEAS; ISSN:2212-8778. (Elsevier GmbH)Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown.In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-wt. men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02:45-07:00 h), and after two nights of normal sleep (NS; sleep opportunity 22:30-07:00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addn., participants underwent an oral glucose tolerance test following each sleep intervention.Microbiota compn. anal. (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes:Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P < 0.05) - previously all assocd. with metabolic perturbations in animal or human models. However, no PSD vs. NS effect on beta diversity or on fecal short-chain fatty acid concns. was found. Fasting and postprandial insulin sensitivity decreased after PSD vs. NS (all P < 0.05).Our findings demonstrate that short-term sleep loss induces subtle effects on human microbiota. To what extent the obsd. changes to the microbial community contribute to metabolic consequences of sleep loss warrants further investigations in larger and more prolonged sleep studies, to also assess how sleep loss impacts the microbiota in individuals who already are metabolically compromised.
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414Zhang, S. L.; Bai, L.; Goel, N.; Bailey, A.; Jang, C. J.; Bushman, F. D.; Meerlo, P.; Dinges, D. F.; Sehgal, A. Human and rat gut microbiome composition is maintained following sleep restriction. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, E1564– E1571, DOI: 10.1073/pnas.1620673114414https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitlGjtb4%253D&md5=9aec22e0fd2e866919821f3abfd6a440Human and rat gut microbiome composition is maintained following sleep restrictionZhang, Shirley L.; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J.; Bushman, Frederic D.; Meerlo, Peter; Dinges, David F.; Sehgal, AmitaProceedings of the National Academy of Sciences of the United States of America (2017), 114 (8), E1564-E1571CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is assocd. with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurol. and cognitive impairments. Shifts in gut microbiome compn. have also been assocd. with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examd. the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or compn. induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.
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415Anderson, J. R.; Carroll, I.; Azcarate-Peril, M. A.; Rochette, A. D.; Heinberg, L. J.; Peat, C.; Steffen, K.; Manderino, L. M.; Mitchell, J.; Gunstad, J. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults. Sleep Med. 2017, 38, 104– 107, DOI: 10.1016/j.sleep.2017.07.018415https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7gs1Krug%253D%253D&md5=0d012c9192a94fefff439edbf9f374deA preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adultsAnderson Jason R; Rochette Amber D; Manderino Lisa M; Carroll Ian; Azcarate-Peril M Andrea; Heinberg Leslie J; Peat Christine; Steffen Kristine; Mitchell James; Gunstad JohnSleep medicine (2017), 38 (), 104-107 ISSN:.OBJECTIVES: Inadequate sleep increases the risk for age-related cognitive decline and recent work suggests a possible role of the gut microbiota in this phenomenon. Partial sleep deprivation alters the human gut microbiome, and its composition is associated with cognitive flexibility in animal models. Given these findings, we examined the possible relationship among the gut microbiome, sleep quality, and cognitive flexibility in a sample of healthy older adults. METHODS: Thirty-seven participants (age 64.59 ± 7.54 years) provided a stool sample for gut microbial sequencing and completed the Pittsburgh Sleep Quality Index and Stroop Color Word Test as part of a larger project. RESULTS: Better sleep quality was associated with better Stroop performance and higher proportions of the gut microbial phyla Verrucomicrobia and Lentisphaerae. Stroop Word and Color-Word performance correlated with higher proportions of Verrucomicrobia and Lentisphaerae. Partial correlations suggested that the relationship between Lentisphaerae and Stroop Color-Word performance was better accounted for by sleep quality; sleep quality remained a significant predictor of Color-Word performance, independent of the Lentisphaerae proportion, while the relationship between Lentisphaerae and Stroop performance was non-significant. Verrucomicrobia and sleep quality were not associated with Stroop Word performance independent of one another. CONCLUSIONS: The current findings suggest a possible relationship among sleep quality, composition of the gut microbiome, and cognitive flexibility in healthy older adults. Prospective and experimental studies are needed to confirm these findings and determine whether improving microbiome health may buffer against sleep-related cognitive decline in older adults.
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416Krueger, J. M.; Opp, M. R. Sleep and Microbes. Int. Rev. Neurobiol. 2016, 131, 207– 225, DOI: 10.1016/bs.irn.2016.07.003416https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsV2gsLvJ&md5=dad2798ad92da44ed4d1658a5ccf585aSleep and microbesKrueger, J. M.; Opp, M. R.International Review of Neurobiology (2016), 131 (Gut Microbiome and Behavior), 207-225CODEN: IRNEAE; ISSN:0074-7742. (Elsevier)Sleep is profoundly altered during the course of infectious diseases. The typical response to infection includes an initial increase in nonrapid eye movement sleep (NREMS) followed by an inhibition in NREMS. REMS is inhibited during infections. Bacterial cell wall components, such as peptidoglycan and lipopolysaccharide, macrophage digests of these components, such as muramyl peptides, and viral products, such as viral double-stranded RNA, trigger sleep responses. They do so via pathogen-assocd. mol. pattern recognition receptors that, in turn, enhance cytokine prodn. Altered sleep and assocd. sleep-facilitated fever responses are likely adaptive responses to infection. Normal sleep in physiol. conditions may also be influenced by gut microbes because the microbiota is affected by circadian rhythms, stressors, diet, and exercise. Furthermore, sleep loss enhances translocation of viable bacteria from the intestine, which provides another means by which sleep-microbe interactions impact neurobiol.
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417Frey, D. J.; Fleshner, M.; Wright, K. P. The effects of 40 h of total sleep deprivation on inflammatory markers in healthy young adults. Brain, Behavior, and Immunity 2007, 21, 1050– 1057, DOI: 10.1016/j.bbi.2007.04.003417https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFSlsb3K&md5=37547bb61f385800507b6d12ba696a28The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adultsFrey, Danielle J.; Fleshner, Monika; Wright, Kenneth P.Brain, Behavior, and Immunity (2007), 21 (8), 1050-1057CODEN: BBIMEW; ISSN:0889-1591. (Elsevier B.V.)Inflammatory cytokines are released in response to stress, tissue damage, and infection. Acutely, this response is adaptive; however, chronic elevation of inflammatory proteins can contribute to health problems including cardiovascular, endocrine, mood, and sleep disorders. Few studies have examd. how sleep deprivation acutely affects inflammatory markers, which was the aim of the current study. Nineteen healthy men and women aged 28.05 ± 8.56 (mean ± SD) were totally sleep deprived for 40 h under const. routine conditions. Pro-inflammatory markers: intracellular adhesion mol.-1 (ICAM-1), E-selectin, vascular adhesion mol.-1 (VCAM-1), c-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) were assayed in plasma. Daytime levels during baseline (hours 1-15 of scheduled wakefulness) were compared to daytime levels during sleep deprivation (hours 25-39 of scheduled wakefulness), thus controlling for circadian phase within an individual. Repeated measures ANOVA with planned comparisons showed that 40 h of total sleep deprivation induced a significant increase in E-selectin, ICAM-1, IL-1β, and IL-1ra, a significant decrease in CRP and IL-6, and no significant change in VCAM-1. Alterations in circulating levels of pro- and anti-inflammatory cytokines and cell adhesion mols. during sleep deprivation were consistent with both increased and decreased inflammation. These findings suggest that one night of sleep loss triggers a stress response that includes stimulation of both pro- and anti-inflammatory proteins in the healthy young subjects tested under our exptl. conditions.
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418Kamada, N.; Seo, S. U.; Chen, G. Y.; Núñez, G. Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 2013, 13, 321– 335, DOI: 10.1038/nri3430418https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmsFahsr0%253D&md5=6b2f2776e4d63244ddc52296b78a7e3eRole of the gut microbiota in immunity and inflammatory diseaseKamada, Nobuhiko; Seo, Sang-Uk; Chen, Grace Y.; Nunez, GabrielNature Reviews Immunology (2013), 13 (5), 321-335CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. The mammalian intestine is colonized by trillions of microorganisms, most of which are bacteria that have co-evolved with the host in a symbiotic relationship. The collection of microbial populations that reside on and in the host is commonly referred to as the microbiota. A principal function of the microbiota is to protect the intestine against colonization by exogenous pathogens and potentially harmful indigenous microorganisms via several mechanisms, which include direct competition for limited nutrients and the modulation of host immune responses. Conversely, pathogens have developed strategies to promote their replication in the presence of competing microbiota. Breakdown of the normal microbial community increases the risk of pathogen infection, the overgrowth of harmful pathobionts and inflammatory disease. Understanding the interaction of the microbiota with pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders.
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419Yasuda, M.; Kato, S.; Yamanaka, N.; Iimori, M.; Matsumoto, K.; Utsumi, D.; Kitahara, Y.; Amagase, K.; Horie, S.; Takeuchi, K. 5-HT3 receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cells. Br. J. Pharmacol. 2013, 168, 1388– 1400, DOI: 10.1111/bph.12019419https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjvVWqsbw%253D&md5=4b61c17a5f35e37d17fe4b1c046082625-HT3 receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cellsYasuda, M.; Kato, S.; Yamanaka, N.; Iimori, M.; Matsumoto, K.; Utsumi, D.; Kitahara, Y.; Amagase, K.; Horie, S.; Takeuchi, K.British Journal of Pharmacology (2013), 168 (6), 1388-1400CODEN: BJPCBM; ISSN:1476-5381. (Wiley-Blackwell)Background and Purpose Chemotherapeutic agents, including 5-fluorouracil (5-FU), frequently cause intestinal mucositis resulting in severe diarrhoea and morphol. mucosal damage. 5-HT3 receptor antagonists are clin. effective in the treatment of nausea and emesis during cancer chemotherapy. Therefore we here have examd. the effects of 5-HT3 receptor antagonists on 5-FU-induced intestinal mucositis in mice. Exptl. Approach Intestinal mucositis was induced in male C57BL/6 mice by daily administration of 5-FU (50 mg·kg-1) for 5 days. Effects of 5-HT3 receptor antagonists, ramosetron (0.01-0.1 mg·kg-1) and ondansetron (5 mg·kg-1), on the accompanying histol., cytokine prodn. and apoptosis were assessed. Key Results Continuous administration of 5-FU to mice caused severe intestinal mucositis, which was histol. characterized by the shortening of villi and destruction of intestinal crypts, accompanied by body wt. loss and diarrhoea. Daily ramosetron administration dose-dependently reduced the severity of intestinal mucositis, body wt. loss and diarrhoea. Similar beneficial effects were obsd. with ondansetron. The no. of apoptotic, caspase-3- and caspase-8-activated cells increased 24 h after the first 5-FU administration, and these responses were reduced by ramosetron. The up-regulation of TNF-α, IL-1β and IL-6 following 5-FU treatment was also attenuated by ramosetron. Conclusions and Implications 5-HT3 receptor antagonists ameliorated 5-FU-induced intestinal mucositis in mice, and this action could result from suppression of apoptotic responses in the intestinal crypt cells via inhibition of cytokine expression. Thus, 5-HT3 receptor antagonists may be useful for preventing not only nausea and emesis but also intestinal mucositis during 5-FU chemotherapy.
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420Li, H.-L.; Lu, L.; Wang, X.-S.; Qin, L.-Y.; Wang, P.; Qiu, S.-P.; Wu, H.; Huang, F.; Zhang, B.-B.; Shi, H.-L. Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis. Frontiers in Cellular and Infection Microbiology 2017, 7, 455, DOI: 10.3389/fcimb.2017.00455420https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVOksLjN&md5=49a68aba1109c9d7c48bea4be7ef51b3Alteration of gut microbiota and inflammatory cytokine/chemokine profiles in 5-fluorouracil induced intestinal mucositisLi, Hong-Li; Lu, Lan; Wang, Xiao-Shuang; Qin, Li-Yue; Wang, Ping; Qiu, Shui-Ping; Wu, Hui; Huang, Fei; Zhang, Bei-Bei; Shi, Hai-Lian; Wu, Xiao-JunFrontiers in Cellular and Infection Microbiology (2017), 7 (), 455/1-455/14CODEN: FCIMAB; ISSN:2235-2988. (Frontiers Media S.A.)Disturbed homeostasis of gut microbiota has been suggested to be closely assocd. with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by wt. loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion mols. such as vascular cell adhesion mol.-1 (VCAM-1), intercellular adhesion mol.-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion mol.-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body wt. loss and colon shortening of 5-Fu treated mice. In addn., the fecal transplant from 5-Fu treated mice reduced body wt. and colon length of vancomycinpretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathol. process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.
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421Benton, D.; Williams, C.; Brown, A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 2007, 61, 355– 361, DOI: 10.1038/sj.ejcn.1602546421https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2s7ivVChtg%253D%253D&md5=53506d17e623536e3f6080844c41d60eImpact of consuming a milk drink containing a probiotic on mood and cognitionBenton D; Williams C; Brown AEuropean journal of clinical nutrition (2007), 61 (3), 355-61 ISSN:0954-3007.OBJECTIVE: The impact on mood and memory of consuming a probiotic containing milk drink, or a placebo, was examined as, previously, a poor mood has been found to correlate with the frequency of constipation. DESIGN: A double-blind placebo-controlled trial with random allocation of subjects. SETTING: Subjects went about their normal life in the community apart from three visits to the laboratory. SUBJECTS: One hundred and thirty-two healthy members of general population, mean age 61.8 years, volunteered in response to local media coverage. One hundred and twenty-four finished the trial. INTERVENTION: For a 3-week period, either a probiotic containing milk drink, or a placebo, were consumed daily. Mood and cognition were measured at baseline, and after 10 and 20 days of consumption. RESULTS: At baseline those who reported themselves to be less frequently constipated were more clearheaded, confident and elated. Although the taking of the probiotic did not generally change the mood, this appeared to be a reflection of the generally good mood in this sample. When those in the bottom third of the depressed/elated dimension at baseline were considered, they selectively responded by reporting themselves as happy rather than depressed after taking the probiotic. The intervention did not, however, influence the reported frequency of defaecation, probably a reflection of the initially low incidence of constipation. An unexpected and possibly chance finding was that the consumption of probiotics resulted in a slightly-poorer performance on two measures of memory. CONCLUSIONS: The consumption of a probiotic-containing yoghurt improved the mood of those whose mood was initially poor. This improvement in mood was not, however, associated with an increased frequency of defaecation.
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422Parkar, S. G.; Kalsbeek, A.; Cheeseman, J. F. Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health. Microorganisms 2019, 7, 41, DOI: 10.3390/microorganisms7020041422https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitlWntbbN&md5=38628e871023dc23d7f7a6421abf671bPotential role for the gut microbiota in modulating host circadian rhythms and metabolic healthParkar, G.; Kalsbeek, Andries; Cheeseman, James F.Microorganisms (2019), 7 (2), 41CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)This article reviews the current evidence assocg. gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of compn., their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivs., vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased prodn. of hydrogen sulfide and the resultant decreased prodn. of butyrate, in turn affect substrate oxidn. and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome assocd. with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis.
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423Zhao, D.; Yu, Y.; Shen, Y.; Liu, Q.; Zhao, Z.; Sharma, R.; Reiter, R. J. Melatonin Synthesis and Function: Evolutionary History in Animals and Plants. Front. Endocrinol. 2019, 10, 249, DOI: 10.3389/fendo.2019.00249423https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7is1Grug%253D%253D&md5=40cfef92a222457727f1c2af3d4e39b8Melatonin Synthesis and Function: Evolutionary History in Animals and PlantsZhao Dake; Zhao Dake; Zhao Dake; Yu Yang; Zhao Zhiwei; Shen Yong; Liu Qin; Sharma Ramaswamy; Reiter Russel JFrontiers in endocrinology (2019), 10 (), 249 ISSN:1664-2392.Melatonin is an ancient molecule that can be traced back to the origin of life. Melatonin's initial function was likely that as a free radical scavenger. Melatonin presumably evolved in bacteria; it has been measured in both α-proteobacteria and in photosynthetic cyanobacteria. In early evolution, bacteria were phagocytosed by primitive eukaryotes for their nutrient value. According to the endosymbiotic theory, the ingested bacteria eventually developed a symbiotic association with their host eukaryotes. The ingested α-proteobacteria evolved into mitochondria while cyanobacteria became chloroplasts and both organelles retained their ability to produce melatonin. Since these organelles have persisted to the present day, all species that ever existed or currently exist may have or may continue to synthesize melatonin in their mitochondria (animals and plants) and chloroplasts (plants) where it functions as an antioxidant. Melatonin's other functions, including its multiple receptors, developed later in evolution. In present day animals, via receptor-mediated means, melatonin functions in the regulation of sleep, modulation of circadian rhythms, enhancement of immunity, as a multifunctional oncostatic agent, etc., while retaining its ability to reduce oxidative stress by processes that are, in part, receptor-independent. In plants, melatonin continues to function in reducing oxidative stress as well as in promoting seed germination and growth, improving stress resistance, stimulating the immune system and modulating circadian rhythms; a single melatonin receptor has been identified in land plants where it controls stomatal closure on leaves. The melatonin synthetic pathway varies somewhat between plants and animals. The amino acid, tryptophan, is the necessary precursor of melatonin in all taxa. In animals, tryptophan is initially hydroxylated to 5-hydroxytryptophan which is then decarboxylated with the formation of serotonin. Serotonin is either acetylated to N-acetylserotonin or it is methylated to form 5-methoxytryptamine; these products are either methylated or acetylated, respectively, to produce melatonin. In plants, tryptophan is first decarboxylated to tryptamine which is then hydroxylated to form serotonin.
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424Wang, B.; Duan, R.; Duan, L. Prevalence of sleep disorder in irritable bowel syndrome: A systematic review with meta-analysis. Saudi J. Gastroenterol. 2018, 24, 141, DOI: 10.4103/sjg.SJG_603_17424https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MjitlKquw%253D%253D&md5=730bd07cbe5b513966dc95fae89e40b2Prevalence of sleep disorder in irritable bowel syndrome: A systematic review with meta-analysisWang Ben; Duan Ruqiao; Duan LipingSaudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association (2018), 24 (3), 141-150 ISSN:.Background/Aims: We conducted this meta-analysis to evaluate the prevalence of sleep disorder in irritable bowel syndrome (IBS) patients and study the association between IBS and sleep disorder. Materials and Methods: A systematic search was conducted by searching PubMed, Embase, and Cochrane library databases using the following search terms: "functional gastrointestinal disorders," "Sleep disturbance," "Sleep disorder," "insomnia," "Dysomnias," "irritable bowel syndrome," and "IBS." Studies evaluating the association between IBS and sleep disorder were identified. Data analysis was conducted using meta-analysis software Comprehensive Meta-Analysis (CMA) 2.0. Heterogeneity across studies was evaluated by χ(2)and I(2)statistics. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Sensitivity analysis was also performed by removing each single study separately. Results: The bibliographical search yielded a total of 2866 studies. Finally, 36 studies including 63620 participants were identified. The prevalence of sleep disorder in IBS was 37.6% (95% CI: 31.4% to 44.3%) based on this meta-analysis. The pooled odds ratio was 2.618 (95% CI: 2.052% to 3.341). Publication bias was not determined. Regarding the sensitivity analysis, the outcome was stable regardless of which study was removed. Conclusions: The prevalence of sleep disorder was higher in IBS compared to healthy controls and may be associated with the pathogenesis of IBS. The prevalence of sleep disorder in IBS may differ according to different areas, age, gender, occupation, and IBS diagnostic criteria. Further studies are needed to investigate any possible causal relationship between sleep disorder and IBS.
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425Miglis, M. G. Autonomic dysfunction in primary sleep disorders. Sleep Med. 2016, 19, 40– 49, DOI: 10.1016/j.sleep.2015.10.001425https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s%252FhsVGruw%253D%253D&md5=fd1b77b45703f3d7f7fff9a04148062dAutonomic dysfunction in primary sleep disordersMiglis Mitchell GSleep medicine (2016), 19 (), 40-9 ISSN:.The autonomic nervous system plays an important role in the coordination of many important physiologic functions during sleep. Many patients with untreated sleep disorders will describe symptoms of autonomic impairment, and a majority of patients with autonomic impairment have some form of sleep disorder. This article will explore possible explanations for this connection, as well as review the current literature on autonomic impairment in common primary sleep disorders including obstructive sleep apnea, insomnia, restless legs syndrome, periodic limb movement disorder, narcolepsy, and rapid eye movement sleep behavior disorder.
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426Tobaldini, E.; Costantino, G.; Solbiati, M.; Cogliati, C.; Kara, T.; Nobili, L.; Montano, N. Sleep, sleep deprivation, autonomic nervous system and cardiovascular diseases. Neurosci Biobehav Rev. 2017, 74, 321– 329, DOI: 10.1016/j.neubiorev.2016.07.004426https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s7osFOhuw%253D%253D&md5=bc2e172ba1b6eb6934d79334fb29fe4eSleep, sleep deprivation, autonomic nervous system and cardiovascular diseasesTobaldini Eleonora; Costantino Giorgio; Solbiati Monica; Cogliati Chiara; Kara Tomas; Nobili Lino; Montano NicolaNeuroscience and biobehavioral reviews (2017), 74 (Pt B), 321-329 ISSN:.Sleep deprivation (SD) has become a relevant health problem in modern societies. We can be sleep deprived due to lifestyle habits or due to sleep disorders, such as insomnia, obstructive sleep apnea (OSA) and neurological disorders. One of the common element of sleep disorders is the condition of chronic SD, which has complex biological consequences. SD is capable of inducing different biological effects, such as neural autonomic control changes, increased oxidative stress, altered inflammatory and coagulatory responses and accelerated atherosclerosis. All these mechanisms links SD and cardiovascular and metabolic disorders. Epidemiological studies have shown that short sleep duration is associated with increased incidence of cardiovascular diseases, such as coronary artery disease, hypertension, arrhythmias, diabetes and obesity, after adjustment for socioeconomic and demographic risk factors and comorbidities. Thus, an early assessment of a condition of SD and its treatment is clinically relevant to prevent the harmful consequences of a very common condition in adult population.
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427Vgontzas, A. N.; Chrousos, G. P. Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. Endocrinol. Metab. Clin. North Am. 2002, 31, 15– 36, DOI: 10.1016/S0889-8529(01)00005-6427https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XkvFensL8%253D&md5=fbdba5b68852ab87b1f623ab49876c40Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disordersVgontzas, Alexandros N.; Chrousos, George P.Endocrinology and Metabolism Clinics of North America (2002), 31 (1), 15-36CODEN: ECNAER; ISSN:0889-8529. (W. B. Saunders Co.)A review. Sleep has an inhibitory effect on the hypothalamic-pituitary-adrenal (HPA) axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is assocd. with a 24-h increase of corticotropin (ACTH) and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. The proinflammatory cytokines IL-6 and TNF-α are increased in disorders assocd. with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia.
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428Schlereth, T.; Birklein, F. The sympathetic nervous system and pain. Neuromolecular Med. 2008, 10, 141– 147, DOI: 10.1007/s12017-007-8018-6428https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXpslSmu7g%253D&md5=aa6a85237f078eb184444d2422b85457The Sympathetic Nervous System and PainSchlereth, Tanja; Birklein, FrankNeuroMolecular Medicine (2008), 10 (3), 141-147CODEN: NMEEAN; ISSN:1535-1084. (Humana Press Inc.)The sympathetic nervous system (SNS) and pain interact on many levels of the neuraxis. In healthy subjects, activation of the SNS in the brain usually suppresses pain mainly by descending inhibition of nociceptive transmission in the spinal cord. Furthermore, some exptl. data even suggest that the SNS might control peripheral inflammation and nociceptive activation. However, even subtle changes in pathophysiol. can dramatically change the effect of SNS on pain, and vice versa. In the periphery, inflammation or nociceptive activation is enhanced, spinal descending inhibition is reversed to spinal facilitation, and finally the awareness of all these changes will induce anxiety, which furthermore amplifies pain perception, affects pain behavior, and depresses mood. Unraveling the detailed mol. mechanisms of how this interaction of SNS and pain is established in health and disease will help us to treat pain more successfully in the future.
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429Wong, R. K.; Yang, C.; Song, G. H.; Wong, J.; Ho, K. Y. Melatonin regulation as a possible mechanism for probiotic (VSL#3) in irritable bowel syndrome: a randomized double-blinded placebo study. Dig. Dis. Sci. 2015, 60, 186– 194, DOI: 10.1007/s10620-014-3299-8429https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlanur%252FI&md5=d79ff1de2d0caca527789357176d18d6Melatonin Regulation as a Possible Mechanism for Probiotic (VSL#3) in Irritable Bowel Syndrome: A Randomized Double-Blinded Placebo StudyWong, Reuben K.; Yang, Cao; Song, Guang-Hui; Wong, Jennie; Ho, Khek-YuDigestive Diseases and Sciences (2015), 60 (1), 186-194CODEN: DDSCDJ; ISSN:0163-2116. (Springer)Background: Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. Aim: The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychol. and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. Methods: Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 wk. Subjects completed bowel and psychol. questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. Results: Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. Conclusions: VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin prodn., hence modulating IBS symptoms, in individuals with a normal circadian rhythm.
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430Zhao, E.; Tait, C.; Minacapelli, C. D.; Catalano, C.; Rustgi, V. K. Circadian Rhythms, the Gut Microbiome, and Metabolic Disorders. Gastro Hep Advances 2022, 1, 93– 105, DOI: 10.1016/j.gastha.2021.10.008There is no corresponding record for this reference.
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431Liang, X.; Bushman, F. D.; FitzGerald, G. A. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc. Natl. Acad. Sci. U. S. A. 2015, 112, 10479– 10484, DOI: 10.1073/pnas.1501305112431https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1ygt7bP&md5=21b0d86495276282bf024e7bebab44d3Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clockLiang, Xue; Bushman, Frederic D.; FitzGerald, Garret A.Proceedings of the National Academy of Sciences of the United States of America (2015), 112 (33), 10479-10484CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)In mammals, multiple physiol., metabolic, and behavioral processes are subject to circadian rhythms, adapting to changing light in the environment. Here we analyzed circadian rhythms in the fecal microbiota of mice using deep sequencing, and found that the abs. amt. of fecal bacteria and the abundance of Bacteroidetes exhibited circadian rhythmicity, which was more pronounced in female mice. Disruption of the host circadian clock by deletion of Bmal1, a gene encoding a core mol. clock component, abolished rhythmicity in the fecal microbiota compn. in both genders. Bmal1 deletion also induced alterations in bacterial abundances in feces, with differential effects based on sex. Thus, although host behavior, such as time of feeding, is of recognized importance, here we show that sex interacts with the host circadian clock, and they collectively shape the circadian rhythmicity and compn. of the fecal microbiota in mice.
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432Paulose, J. K.; Wright, J. M.; Patel, A. G.; Cassone, V. M. Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity. PLoS One 2016, 11, e0146643 DOI: 10.1371/journal.pone.0146643432https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisVKgu78%253D&md5=66c63528753d2603bd2d71785a8ee81cHuman gut bacteria are sensitive to melatonin and express endogenous circadian rhythmicityPaulose, Jiffin K.; Wright, John M.; Patel, Akruti G.; Cassone, Vincent M.PLoS One (2016), 11 (1), e0146643/1-e0146643/13CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)Circadian rhythms are fundamental properties of most eukaryotes, but evidence of biol. clocks that drive these rhythms in prokaryotes has been restricted to Cyanobacteria. In vertebrates, the gastrointestinal system expresses circadian patterns of gene expression, motility and secretion in vivo and in vitro, and recent studies suggest that the enteric microbiome is regulated by the host's circadian clock. However, it is not clear how the host's clock regulates the microbiome. Here, we demonstrate at least one species of commensal bacterium from the human gastrointestinal system, Enterobacter aerogenes, is sensitive to the neurohormone melatonin, which is secreted into the gastrointestinal lumen, and expresses circadian patterns of swarming and motility. Melatonin specifically increases the magnitude of swarming in cultures of E. aerogenes, but not in Escherichia coli or Klebsiella pneumoniae. The swarming appears to occur daily, and transformation of E. aerogenes with a flagellar motor-protein driven lux plasmid confirms a temp.-compensated circadian rhythm of luciferase activity, which is synchronized in the presence of melatonin. Altogether, these data demonstrate a circadian clock in a non-cyanobacterial prokaryote and suggest the human circadian system may regulate its microbiome through the entrainment of bacterial clocks.
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433Mukherji, A.; Kobiita, A.; Ye, T.; Chambon, P. Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 2013, 153, 812– 827, DOI: 10.1016/j.cell.2013.04.020433https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsFSmtb0%253D&md5=92e774e6925c70c2bf0ba544d0d0f8e2Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRsMukherji, Atish; Kobiita, Ahmad; Ye, Tao; Chambon, PierreCell (Cambridge, MA, United States) (2013), 153 (4), 812-827CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Alterations of symbiosis between microbiota and intestinal epithelial cells (IEC) are assocd. with intestinal and systemic pathologies. Interactions between bacterial products (MAMPs) and Toll-like receptors (TLRs) are known to be mandatory for IEC homeostasis, but how TLRs may time homeostatic functions with circadian changes is unknown. Our functional and mol. dissections of the IEC circadian clock demonstrate that its integrity is required for microbiota-IEC dialog. In IEC, the antiphasic expression of the RORα activator and RevErbα repressor clock output regulators generates a circadian rhythmic TLR expression that converts the temporally arrhythmic microbiota signaling into circadian rhythmic JNK and IKKβ activities, which prevents RevErbα activation by PPARα that would disrupt the circadian clock. Moreover, through activation of AP1 and NF-κB, these activities, together with RORα and Rev-Erbα, enable timing homeostatic functions of numerous genes with IEC circadian events. Interestingly, microbiota signaling deficiencies induce a prediabetic syndrome due to ileal corticosterone overprodn. consequent to clock disruption.
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434Paschos, G. K.; FitzGerald, G. A. Circadian Clocks and Metabolism: Implications for Microbiome and Aging. Trends Genet. 2017, 33, 760– 769, DOI: 10.1016/j.tig.2017.07.010434https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXht1ygu7rO&md5=7484d224885089e3d0ab0afd749b7e09Circadian Clocks and Metabolism: Implications for Microbiome and AgingPaschos, Georgios K.; FitzGerald, Garret A.Trends in Genetics (2017), 33 (10), 760-769CODEN: TRGEE2; ISSN:0168-9525. (Elsevier Ltd.)The circadian clock directs many aspects of metab., to sep. in time opposing metabolic pathways and optimize metabolic efficiency. The master circadian clock of the suprachiasmatic nucleus synchronizes to light, while environmental cues such as temp. and feeding, out of phase with the light schedule, may synchronize peripheral clocks. This misalignment of central and peripheral clocks may be involved in the development of disease and the acceleration of aging, possibly in a gender-specific manner. Here we discuss the interplay between the circadian clock and metab., the importance of the microbiome, and how they relate to aging.
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435Fernandez-Real, J. M.; Serino, M.; Blasco, G.; Puig, J.; Daunis-i-Estadella, J.; Ricart, W.; Burcelin, R.; Fernández-Aranda, F.; Portero-Otin, M. Gut Microbiota Interacts With Brain Microstructure and Function. J. Clin Endocrinol Metab 2015, 100, 4505– 4513, DOI: 10.1210/jc.2015-3076435https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XjtlSntr0%253D&md5=0cc5aed4e2adb94468aa404d91f622caGut microbiota interacts with brain microstructure and functionFernandez-Real, Jose-Manuel; Serino, Matteo; Blasco, Gerard; Puig, Josep; Daunis-i-Estadella, Josep; Ricart, Wifredo; Burcelin, Remy; Fernandez-Aranda, Fernando; Portero-Otin, ManuelJournal of Clinical Endocrinology and Metabolism (2015), 100 (12), 4505-4513CODEN: JCEMAZ; ISSN:0021-972X. (Endocrine Society)Context: Evidence from animals suggests that gut microbiota affects brain structure and function but evidence in humans is scarce. Objective: This study sought to evaluate potential interactions among gut microbiota compn., brain microstructure, and cognitive tests in obese and nonobese subjects. Design, Setting, and Participants: This was a cross-sectional study at a tertiary hospital including 20 consecutive obese and 19 nonobese subjects similar in age and sex. Main Outcome Measures: Gut microbiota (16S bacterial gene pyrosequencing), brain microstructure (diffusion tensor imaging of brain white and gray matter and R2* sequences in magnetic resonance imaging) and cognitive tests. Results: Hierarchical clustering revealed a specific gut microbiota-brain map profile for obese individuals who could be discriminated from nonobese subjects (accuracy of 0.81). Strikingly, Shannon index was linked to R2* and fractional anisotropy of the hypothalamus, caudate nucleus, and hippocampus, suggesting sparing of these brain structures with increased bacterial biodiversity. Microbiota profile also clustered with cognitive function. The relative abundance of Actinobacteria phylum was linked not only to magnetic resonance imaging diffusion tensor imaging variables in the thalamus, hypothalamus, and amygdala but also to cognitive test scores related to speed, attention, and cognitive flexibility. Conclusions: In sum, obesity status affects microbiota-brain microstructure and function crosstalk.
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436Carlson, A. L.; Xia, K.; Azcarate-Peril, M. A.; Goldman, B. D.; Ahn, M.; Styner, M. A.; Thompson, A. L.; Geng, X.; Gilmore, J. H.; Knickmeyer, R. C. Infant Gut Microbiome Associated With Cognitive Development. Biol. Psychiatry 2018, 83, 148– 159, DOI: 10.1016/j.biopsych.2017.06.021436https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cfmtFKhug%253D%253D&md5=da5db5d0f67c9c3f8f710957f5098af7Infant Gut Microbiome Associated With Cognitive DevelopmentCarlson Alexander L; Xia Kai; Gilmore John H; Azcarate-Peril M Andrea; Goldman Barbara D; Ahn Mihye; Styner Martin A; Thompson Amanda L; Geng Xiujuan; Knickmeyer Rebecca CBiological psychiatry (2018), 83 (2), 148-159 ISSN:.BACKGROUND: Studies in rodents provide compelling evidence that microorganisms inhabiting the gut influence neurodevelopment. In particular, experimental manipulations that alter intestinal microbiota impact exploratory and communicative behaviors and cognitive performance. In humans, the first years of life are a dynamic time in gut colonization and brain development, but little is known about the relationship between these two processes. METHODS: We tested whether microbial composition at 1 year of age is associated with cognitive outcomes using the Mullen Scales of Early Learning and with global and regional brain volumes using structural magnetic resonance imaging at 1 and 2 years of age. Fecal samples were collected from 89 typically developing 1-year-olds. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. RESULTS: Cluster analysis identified 3 groups of infants defined by their bacterial composition. Mullen scores at 2 years of age differed significantly between clusters. In addition, higher alpha diversity was associated with lower scores on the overall composite score, visual reception scale, and expressive language scale at 2 years of age. Exploratory analyses of neuroimaging data suggest the gut microbiome has minimal effects on regional brain volumes at 1 and 2 years of age. CONCLUSIONS: This is the first study to demonstrate associations between the gut microbiota and cognition in human infants. As such, it represents an essential first step in translating animal data into the clinic.
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437Polidano, C.; Zhu, A.; Bornstein, J. C. The relation between cesarean birth and child cognitive development. Sci. Rep. 2017, 7, 11483, DOI: 10.1038/s41598-017-10831-y437https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cbnvFCnug%253D%253D&md5=51bd54f42e44da3394ee875c78c1bab4The relation between cesarean birth and child cognitive developmentPolidano Cain; Zhu Anna; Bornstein Joel CScientific reports (2017), 7 (1), 11483 ISSN:.This is the first detailed study of the relation between cesarean birth and child cognitive development. We measure differences in child cognitive performance at 4 to 9 years of age between cesarean-born and vaginally-born children (n = 3,666) participating in the Longitudinal Study of Australian Children (LSAC). LSAC is a nationally representative birth cohort surveyed biennially. Using multivariate regression, we control for a large range of confounders related to perinatal risk factors and the socio-economic advantage associated with cesarean-born children. Across several measures, we find that cesarean-born children perform significantly below vaginally-born children, by up to a tenth of a standard deviation in national numeracy test scores at age 8-9. Estimates from a low-risk sub-sample and lower-bound analysis suggest that the relation is not spuriously related to unobserved confounding. Lower rates of breastfeeding and adverse child and maternal health outcomes that are associated with cesarean birth are found to explain less than a third of the cognitive gap, which points to the importance of other mechanisms such as disturbed gut microbiota. The findings underline the need for a precautionary approach in responding to requests for a planned cesarean when there are no apparent elevated risks from vaginal birth.
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438Chung, Y.-C.; Jin, H.-M.; Cui, Y.; Kim, D. S.; Jung, J. M.; Park, J.-I.; Jung, E.-S.; Choi, E.-K.; Chae, S.-W. Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adults. J. Funct. Foods 2014, 10, 465– 474, DOI: 10.1016/j.jff.2014.07.007438https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtlamsrnL&md5=ab84d274bb605567faa4570a68a5e4a0Fermented milk of Lactobacillus helveticus IDCC3801 improves cognitive functioning during cognitive fatigue tests in healthy older adultsChung, Young-Chul; Jin, Hong-Mei; Cui, Yin; Kim, Dal Sik; Jung, Jin Mu; Park, Jong-Il; Jung, Eun-Soo; Choi, Eun-Kyung; Chae, Soo-WanJournal of Functional Foods (2014), 10 (), 465-474CODEN: JFFOAX; ISSN:1756-4646. (Elsevier Ltd.)Probiotics are consumed in a wide variety of fermented foods to improve health. This study was conducted to investigate the effects of Lactobacillus helveticus-fermented milk (LHFM), on cognitive function in healthy older adults. A 12-wk, double-blind, randomized controlled expt. was conducted. Cognitive tests (neuropsychol. and cognitive fatigue) and measurements of the perceived stress scale (PSS), geriatric depression scale-short form (GDS-SF), brain-derived neurotrophic factor (BDNF) and whole blood viscosity (WBV) were conducted before and after the expt. The administration of LHFM for 12 wk in healthy older adults produced improvement on cognitive tests compared to the placebo group. However, no significant effects were obsd. for PSS, GDS-SF, BDNF, and WBV. Thus, consumption of LHFM might be beneficial for improving cognitive function.
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439Tillisch, K.; Labus, J.; Kilpatrick, L.; Jiang, Z.; Stains, J.; Ebrat, B.; Guyonnet, D.; Legrain-Raspaud, S.; Trotin, B.; Naliboff, B. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 2013, 144, 1394– 1401.e4, DOI: 10.1053/j.gastro.2013.02.043439https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXntV2hsbc%253D&md5=8e502d60712e23b3d1c4a0f95ced0dbdConsumption of Fermented Milk Product With Probiotic Modulates Brain ActivityTillisch, Kirsten; Labus, Jennifer; Kilpatrick, Lisa; Jiang, Zhiguo; Stains, Jean; Ebrat, Bahar; Guyonnet, Denis; Legrain Raspaud, Sophie; Trotin, Beatrice; Naliboff, Bruce; Mayer, Emeran A.Gastroenterology (2013), 144 (7), 1394-1401.e4CODEN: GASTAB; ISSN:0016-5085. (Elsevier)Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 wk by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 wk. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed.FMPP intake was assocd. with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) contg. affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was assocd. with changes in midbrain connectivity, which could explain the obsd. differences in activity during the task. Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation.
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440Smith, A. P.; Sutherland, D.; Hewlett, P. An Investigation of the Acute Effects of Oligofructose-Enriched Inulin on Subjective Wellbeing, Mood and Cognitive Performance. Nutrients 2015, 7, 8887– 8896, DOI: 10.3390/nu7115441440https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVKitrvF&md5=0216a2d1e0dd330812f879fcd3e0b822An investigation of the acute effects of oligofructose-enriched inulin on subjective wellbeing, mood and cognitive performanceSmith, Andrew P.; Sutherland, David; Hewlett, PaulNutrients (2015), 7 (11), 8887-8896CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)Inulin is a natural food component found in many plants that are part of the human diet (e.g., leeks, onions, wheat, garlic, chicory and artichokes). It is added to many foods and is used to increase dietary fiber, replace fats or carbohydrates, and as a prebiotic (a stimulant of beneficial bacteria in the colon). Oligofructose, which is also present in these foods, produces similar effects and most research has used a combination of these products. A previous study (Smith, 2005) investigated the effects of regular consumption of oligofructose-enriched inulin on wellbeing, mood, and cognitive performance in humans. The results showed that oligofructose-enriched inulin had no neg. effects but that it did not improve wellbeing, mood, or performance. The aim of the present study was to examine the acute effects of oligofructose-enriched inulin (5 g) over a 4 h period during which the participants remained in the lab. A double blind placebo (maltodextrin) controlled study (N = 47) was carried out with the order of conditions being counterbalanced and the two sessions a week apart. On each test day mood and cognitive performance were assessed at baseline (at 8:00) and then following inulin or placebo (at 11:00). Prior to the second test session (at 10:30) participants completed a questionnaire assessing their phys. symptoms and mental health during the test morning. The inulin and placebo were provided in powder form in 5 g sachets. Volunteers consumed one sachet in decaffeinated tea or decaffeinated coffee with breakfast (9:00). Questionnaire results showed that on the day that the inulin was consumed, participants felt happier, had less indigestion and were less hungry than when they consumed the placebo. As for performance and mood tasks, the most consistent effects were on the episodic memory tasks where consumption of inulin was assocd. with greater accuracy on a recognition memory task, and improved recall performance (immediate and delayed). Further research is required to identify the mechanisms that underlie this effect with glucose metab. being one candidate.
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441Lee, S.-H.; Yoon, S.-H.; Jung, Y.; Kim, N.; Min, U.; Chun, J.; Choi, I. Emotional well-being and gut microbiome profiles by enterotype. Sci. Rep. 2020, 10, 20736, DOI: 10.1038/s41598-020-77673-z441https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisFShtrvP&md5=b631f1f52bec181eadc3b0aa7bcb82d4Emotional well-being and gut microbiome profiles by enterotypeLee, Sung-Ha; Yoon, Seok-Hwan; Jung, Yeonjae; Kim, Namil; Min, Uigi; Chun, Jongsik; Choi, IncheolScientific Reports (2020), 10 (1), 20736CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Abstr.: With increasing attention being paid to improving emotional well-being, recent evidence points to gut microbiota as a key player in regulating mental and phys. health via bidirectional communication between the brain and gut. Here, we examine the assocn. between emotional well-being and gut microbiome profiles (i.e., gut microbiome compn., diversity, and the moderating role of the enterotypes) among healthy Korean adults (n = 83, mean age = 48.9, SD = 13.2). The research was performed using high-throughput 16S rRNA gene sequencing to obtain gut microbiome profiles, as well as a self-report survey that included the Pos. Affect Neg. Affect Schedule (PANAS). The cluster-based anal. identified two enterotypes dominated by the genera Bacteroides (n = 49) and Prevotella (n = 34). Generalized linear regression anal. reveals significant assocns. between pos. emotion and gut microbiome diversity (Shannon Index) among participants in the Prevotella dominant group, whereas no such relationship emerged among participants in the Bacteroides group. Moreover, a novel genus from the family Lachnospiraceae is assocd. with emotional well-being scores, both pos. and neg. Together, the current findings highlight the enterotype-specific links between the gut microbiota community and emotion in healthy adults and suggest the possible roles of the gut microbiome in promoting mental health.
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442Gros, D. F.; Antony, M. M.; McCabe, R. E.; Swinson, R. P. Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depression. J. Anxiety Disord. 2009, 23, 290– 296, DOI: 10.1016/j.janxdis.2008.08.004442https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M3htVWktQ%253D%253D&md5=5d733c6bb4cb72b961aedf020212c1f2Frequency and severity of the symptoms of irritable bowel syndrome across the anxiety disorders and depressionGros Daniel F; Antony Martin M; McCabe Randi E; Swinson Richard PJournal of anxiety disorders (2009), 23 (2), 290-6 ISSN:.High rates of irritable bowel syndrome (IBS) symptoms have been reported in individuals diagnosed with anxiety and depressive disorders. However, most studies have investigated these relations in a single disorder, rather than a heterogeneous group of patients, thereby not allowing for comparisons across anxiety disorders and depression, or for considering the effects of comorbidity. Thus, the present study investigated the symptoms of IBS in a diverse group of patients (N=357) by administering questionnaires and a diagnostic interview. A high frequency of IBS symptoms was found in patients with panic disorder, generalized anxiety disorder, and major depressive disorder. However, the frequency of IBS symptoms in patients with social anxiety disorder, specific phobia, and obsessive-compulsive disorder was comparable to rates found in community samples. In addition, anxiety sensitivity and illness attitudes and intrusiveness were predictive of elevated IBS symptomatology. Together, these findings emphasize the role physiological symptoms of anxiety and worry in the co-occurrence of the anxiety disorders and IBS.
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443Mayer, E. A.; Labus, J. S.; Tillisch, K.; Cole, S. W.; Baldi, P. Towards a systems view of IBS. Nat. Rev. Gastroenterol. Hepatol. 2015, 12, 592– 605, DOI: 10.1038/nrgastro.2015.121443https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsVartb%252FO&md5=f4e08efb2d474e9dd01e6d651bc10d9dTowards a systems view of IBSMayer, Emeran A.; Labus, Jennifer S.; Tillisch, Kirsten; Cole, Steven W.; Baldi, PierreNature Reviews Gastroenterology & Hepatology (2015), 12 (10), 592-605CODEN: NRGHA9; ISSN:1759-5045. (Nature Publishing Group)Despite an extensive body of reported information about peripheral and central mechanisms involved in the pathophysiol. of IBS symptoms, no comprehensive disease model has emerged that would guide the development of novel, effective therapies. In this Review, we will first describe novel insights into some key components of brain-gut interactions, starting with the emerging findings of distinct functional and structural brain signatures of IBS. We will then point out emerging correlations between these brain networks and genomic, gastrointestinal, immune and gut-microbiome-related parameters. We will incorporate this new information, as well as the reported extensive literature on various peripheral mechanisms, into a systems-based disease model of IBS, and discuss the implications of such a model for improved understanding of the disorder, and for the development of more-effective treatment approaches in the future.
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444Zhang, J.; Ma, L.; Chang, L.; Pu, Y.; Qu, Y.; Hashimoto, K. A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration. Translational Psychiatry 2020, 10, 186, DOI: 10.1038/s41398-020-00878-3444https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtFemurzK&md5=61f60452ccdbade0de95b7c628eb1bcbA key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administrationZhang, Jiancheng; Ma, Li; Chang, Lijia; Pu, Yaoyu; Qu, Youge; Hashimoto, KenjiTranslational Psychiatry (2020), 10 (1), 186CODEN: TPRSCF; ISSN:2158-3188. (Nature Research)Abstr.: The vagus nerve plays a role in the cross talk between the brain and gut microbiota, which could be involved in depression. The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Here, we investigated the effects of subdiaphragmatic vagotomy (SDV) on the depression-like phenotype and the abnormal compn. of gut microbiota in mice after lipopolysaccharide (LPS) administration. LPS caused a depression-like phenotype, inflammation, increase in spleen wt., and downregulation of synaptic proteins in the medial prefrontal cortex (mPFC) in the sham-operated mice. In contrast, LPS did not produce a depression-like phenotype and downregulated synaptic proteins in the mPFC after SDV. The spleen wt. and plasma levels of pro-inflammatory cytokines in the SDV + LPS group were lower than those of the sham + LPS group. Interestingly, there were pos. correlations between the plasma levels of pro-inflammatory cytokines and spleen wt., suggesting a relationship between inflammatory events and spleen wt. Furthermore, LPS led to significant alterations in gut microbiota diversity in sham-operated mice, but not SDV-operated mice. In an unweighted UniFrac PCoA, the dots representing the sham + LPS group were located far away from the dots representing the other three groups. Our results suggest that LPS produces a depression-like phenotype, increases spleen wt., triggers inflammation, downregulates synaptic proteins in the mPFC, and leads to abnormal compn. of gut microbiota via the subdiaphragmatic vagus nerve. It is likely that the vagus nerve plays a crucial role in the brain-gut-microbiota axis.
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445Pu, Y.; Tan, Y.; Qu, Y.; Chang, L.; Wang, S.; Wei, Y.; Wang, X.; Hashimoto, K. A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes. Brain, Behavior, and Immunity 2021, 94, 318– 326, DOI: 10.1016/j.bbi.2020.12.032445https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXks1GmsLg%253D&md5=6fa3a523797005c53ffaae8eeadd5e13A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypesPu, Yaoyu; Tan, Yunfei; Qu, Youge; Chang, Lijia; Wang, Siming; Wei, Yan; Wang, Xingming; Hashimoto, KenjiBrain, Behavior, and Immunity (2021), 94 (), 318-326CODEN: BBIMEW; ISSN:0889-1591. (Elsevier Inc.)The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) regulates the cholinergic ascending anti-inflammatory pathway involved in depression. We previously reported that Chrna7 knock-out (KO) mice show depression-like phenotypes through systemic inflammation. In this study, we investigated whether fecal microbiota transplantation (FMT) from Chrna7 KO mice causes depression-like phenotypes in mice treated with an antibiotic cocktail (ABX). Chrna7 KO mice with depression-like phenotypes show an abnormal gut microbiota compn., although the alpha diversity and beta diversity were not altered. FMT from Chrna7 KO mice caused depression-like phenotypes, systemic inflammation, and downregulation of synaptic proteins in the prefrontal cortex (PFC) in the ABX-treated mice compared to FMT from the control mice. The Principal component anal. based on the OTU level showed that the FMT group from the KO mice were different from the FMT group from the control mice. We found differences in abundance for several bacteria in the FMT group from the KO mice at the taxonomic level when compared with the other group. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of depression-like phenotypes in the ABX-treated mice after FMT from Chrna7 KO mice. These data suggest that FMT from Chrna7 KO mice produce depression-like phenotypes in ABX-treated mice via the subdiaphragmatic vagus nerve. The brain-gut-microbiota axis assocn. with the subdiaphragmatic vagus nerve plays an important role in the development of depression.
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446Bruch, J. D. Intestinal infection associated with future onset of an anxiety disorder: Results of a nationally representative study. Brain. Behav. Immun. 2016, 57, 222– 226, DOI: 10.1016/j.bbi.2016.05.014446https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2s%252FjtFGhsA%253D%253D&md5=c7c22b1e692bd2dad0e5d60738023742Intestinal infection associated with future onset of an anxiety disorder: Results of a nationally representative studyBruch Joseph DBrain, behavior, and immunity (2016), 57 (), 222-226 ISSN:.Recent research involving mice suggests a possible relationship between intestinal infection and future anxiety-like behavior. However, there has been little epidemiological research showing such a connection in humans. This study uses the Medical Expenditure Panel Survey (MEPS) to assess longitudinally the association between intestinal infection and later onset of an anxiety disorder, through a nationally representative sample. Six 2-year panel datasets, each comprised of 5 consecutive rounds, were pooled from 2007 to 2013 to gather records for all respondents 18years of age or older that did not have an anxiety disorder in Round 1 (n=63, 133 people). Within the study sample, there were 2577 individuals with an intestinal infection in Round 1 and 4239 individuals with an anxiety disorder that began in Round 2, 3, 4, or 5. Overall, intestinal infection in Round 1 was associated with a 1.34 (P<0.01) odds ratio of having an anxiety disorder that began in Round 2, 3, 4, or 5. Separate analyses were performed to determine whether the association applied to other infection types, including respiratory infection, urinary tract infection, hepatitis infection, and skin infection. Respiratory infection was associated with a 1.36 (P<0.01) odds ratio of having an anxiety disorder that began in Round 2, 3, 4, or 5; no other infection type showed a significant association. More research on human populations is needed to examine the apparent association and explore potential mechanisms by which gut pathogens might influence anxiety.
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447Kiecolt-Glaser, J. K.; Wilson, S. J.; Shrout, M. R.; Madison, A. A.; Andridge, R.; Peng, J.; Malarkey, W. B.; Bailey, M. T. The gut reaction to couples’ relationship troubles: A route to gut dysbiosis through changes in depressive symptoms. Psychoneuroendocrinology 2021, 125, 105132, DOI: 10.1016/j.psyneuen.2021.105132447https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXktFygtL8%253D&md5=e9c4ae7fed44cf1523cdc8ec6b5cc329The gut reaction to couples' relationship troubles: A route to gut dysbiosis through changes in depressive symptomsKiecolt-Glaser, Janice K.; Wilson, Stephanie J.; Shrout, M. Rosie; Madison, Annelise A.; Andridge, Rebecca; Peng, Juan; Malarkey, William B.; Bailey, Michael T.Psychoneuroendocrinology (2021), 125 (), 105132CODEN: PSYCDE; ISSN:0306-4530. (Elsevier Ltd.)The gut microbiota plays a role in a wide range of diseases and disorders, with low microbial diversity and richness emerging as notable risk factors. This longitudinal study addressed the impact of marital quality (assessed by the Couples Satisfaction Index) on changes in depressive symptoms, and gut diversity, richness, and permeability. On two occasions an av. of 90 days apart, 162 people provided stool and blood samples, and completed questionnaires. Depressive symptoms, assessed by the Center for Epidemiol. Studies Depression Scale (CES-D), increased from visit 1 to visit 2 in those with clin. significant relationship problems, in contrast to the lack of change among their more satisfied counterparts. These changes in depression were consequential: the gut microbiota's diversity and richness decreased in tandem with the increase in depressive symptoms. Lower relationship satisfaction also foreshadowed increases in lipopolysaccharide binding protein from visit 1 to visit 2, reflecting greater translocation of bacterial endotoxin from the gut to blood circulation, a process that fuels inflammation. Lower diversity and richness provide a pathway from depressive symptoms and marital distress to subsequent health risk.
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448Kim, H. N.; Yun, Y.; Ryu, S.; Chang, Y.; Kwon, M. J.; Cho, J.; Shin, H.; Kim, H. L. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain. Behav. Immun. 2018, 69, 374– 385, DOI: 10.1016/j.bbi.2017.12.012448https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1Mzlt1ChsQ%253D%253D&md5=d42ed7e6a1ec1dbc0c9b0433cec20765Correlation between gut microbiota and personality in adults: A cross-sectional studyKim Han-Na; Yun Yeojun; Ryu Seungho; Chang Yoosoo; Kwon Min-Jung; Cho Juhee; Shin Hocheol; Kim Hyung-LaeBrain, behavior, and immunity (2018), 69 (), 374-385 ISSN:.Personality affects fundamental behavior patterns and has been related with health outcomes and mental disorders. Recent evidence has emerged supporting a relationship between the microbiota and behavior, referred to as brain-gut relationships. Here, we first report correlations between personality traits and gut microbiota. This research was performed using the Revised NEO Personality Inventory and the sequencing data of the 16S rRNA gene in 672 adults. The diversity and the composition of the human gut microbiota exhibited significant difference when stratified by personality traits. We found that personality traits were significantly correlated with diversity of gut microbiota, while their differences were extremely subtle. High neuroticism and low conscientiousness groups were correlated with high abundance of Gammaproteobacteria and Proteobacteria, respectively when covariates, including age, sex, BMI and nutrient intake, were controlled. Additionally, high conscientiousness group also showed increased abundance of some universal butyrate-producing bacteria including Lachnospiraceae. This study was of observational and cross-sectional design and our findings must be further validated through metagenomic or metatranscriptomic methodologies, or metabolomics-based analyses. Our findings will contribute to elucidating potential links between the gut microbiota and personality, and provide useful insights toward developing and testing personality- and microbiota-based interventions for promoting health.
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449Valles-Colomer, M.; Falony, G.; Darzi, Y.; Tigchelaar, E. F.; Wang, J.; Tito, R. Y.; Schiweck, C.; Kurilshikov, A.; Joossens, M.; Wijmenga, C. The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology 2019, 4, 623– 632, DOI: 10.1038/s41564-018-0337-x449https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmtFKhsbo%253D&md5=7cda15fafdf7111f9a9b90136944511fThe neuroactive potential of the human gut microbiota in quality of life and depressionValles-Colomer, Mireia; Falony, Gwen; Darzi, Youssef; Tigchelaar, Ettje F.; Wang, Jun; Tito, Raul Y.; Schiweck, Carmen; Kurilshikov, Alexander; Joossens, Marie; Wijmenga, Cisca; Claes, Stephan; Van Oudenhove, Lukas; Zhernakova, Alexandra; Vieira-Silva, Sara; Raes, JeroenNature Microbiology (2019), 4 (4), 623-632CODEN: NMAICH; ISSN:2058-5276. (Nature Research)The relationship between gut microbial metab. and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota-gut-brain communication has mostly been explored in animal models, with human research lagging behind. Large-scale metagenomics studies could facilitate the translational process, but their interpretation is hampered by a lack of dedicated ref. databases and tools to study the microbial neuroactive potential. Surveying a large microbiome population cohort (Flemish Gut Flora Project, n = 1,054) with validation in independent data sets (ntotal = 1,070), we studied how microbiome features correlate with host quality of life and depression. Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently assocd. with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants. Using a module-based anal. framework, we assembled a catalog of neuroactive potential of sequenced gut prokaryotes. Gut-brain module anal. of fecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating pos. with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid prodn. in depression. Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.
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450Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D. R.; Fernandes, G. R.; Tap, J.; Bruls, T.; Batto, J.-M. Enterotypes of the human gut microbiome. Nature 2011, 473, 174– 180, DOI: 10.1038/nature09944450https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXkvFeisLo%253D&md5=3f8dfb6b1250d9d913e9ecd03984d9d7Enterotypes of the human gut microbiomeArumugam, Manimozhiyan; Raes, Jeroen; Pelletier, Eric; Le Paslier, Denis; Yamada, Takuji; Mende, Daniel R.; Fernandes, Gabriel R.; Tap, Julien; Bruls, Thomas; Batto, Jean-Michel; Bertalan, Marcelo; Borruel, Natalia; Casellas, Francesc; Fernandez, Leyden; Gautier, Laurent; Hansen, Torben; Hattori, Masahira; Hayashi, Tetsuya; Kleerebezem, Michiel; Kurokawa, Ken; Leclerc, Marion; Levenez, Florence; Manichanh, Chaysavanh; Nielsen, H. Bjorn; Nielsen, Trine; Pons, Nicolas; Poulain, Julie; Qin, Junjie; Sicheritz-Ponten, Thomas; Tims, Sebastian; Torrents, David; Ugarte, Edgardo; Zoetendal, Erwin G.; Wang, Jun; Guarner, Francisco; Pedersen, Oluf; de Vos, Willem M.; Brunak, Soren; Dore, Joel; Weissenbach, Jean; Ehrlich, S. Dusko; Bork, Peer; Antolin, Maria; Artiguenave, Francois; Blottiere, Herve M.; Almeida, Mathieu; Brechot, Christian; Cara, Carlos; Chervaux, Christian; Cultrone, Antonella; Delorme, Christine; Denariaz, Gerard; Dervyn, Rozenn; Foerstner, Konrad U.; Friss, Carsten; van de Guchte, Maarten; Guedon, Eric; Haimet, Florence; Huber, Wolfgang; van Hylckama-Vlieg, Johan; Jamet, Alexandre; Juste, Catherine; Kaci, Ghalia; Knol, Jan; Lakhdari, Omar; Layec, Severine; Le Roux, Karine; Maguin, Emmanuelle; Merieux, Alexandre; Melo Minardi, Raquel; M'rini, Christine; Muller, Jean; Oozeer, Raish; Parkhill, Julian; Renault, Pierre; Rescigno, Maria; Sanchez, Nicolas; Sunagawa, Shinichi; Torrejon, Antonio; Turner, Keith; Vandemeulebrouck, Gaetana; Varela, Encarna; Winogradsky, Yohanan; Zeller, GeorgNature (London, United Kingdom) (2011), 473 (7346), 174-180CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Our knowledge of species and functional compn. of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced fecal metagenomes of individuals from four countries with previously published data sets, the authors identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. They also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited no. of well balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species compn., but abundant mol. functions are not necessarily provided by abundant species, highlighting the importance of a functional anal. to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the obsd. enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
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451Costello, E. K.; Lauber, C. L.; Hamady, M.; Fierer, N.; Gordon, J. I.; Knight, R. Bacterial community variation in human body habitats across space and time. Science 2009, 326, 1694– 1697, DOI: 10.1126/science.1177486451https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFGmsL7K&md5=bc016e97bdcd143c0d46e2b8d496953bBacterial Community Variation in Human Body Habitats Across Space and TimeCostello, Elizabeth K.; Lauber, Christian L.; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I.; Knight, RobScience (Washington, DC, United States) (2009), 326 (5960), 1694-1697CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Elucidating the biogeog. of bacterial communities on the human body is crit. for establishing healthy baselines from which to detect differences assocd. with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in seven to nine healthy adults on four occasions. We found that community compn. was detd. primarily by body habitat. Within habitats, interpersonal variability was high, whereas individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time; such trends may ultimately reveal how microbiome changes cause or prevent disease.
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452Wu, G. D.; Chen, J.; Hoffmann, C.; Bittinger, K.; Chen, Y. Y.; Keilbaugh, S. A.; Bewtra, M.; Knights, D.; Walters, W. A.; Knight, R. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011, 334, 105– 108, DOI: 10.1126/science.1208344452https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1Gms77K&md5=da31735ba897d48e54758aeba1dfa913Linking Long-Term Dietary Patterns with Gut Microbial EnterotypesWu, Gary D.; Chen, Jun; Hoffmann, Christian; Bittinger, Kyle; Chen, Ying-Yu; Keilbaugh, Sue A.; Bewtra, Meenakshi; Knights, Dan; Walters, William A.; Knight, Rob; Sinha, Rohini; Gilroy, Erin; Gupta, Kernika; Baldassano, Robert; Nessel, Lisa; Li, Hongzhe; Bushman, Frederic D.; Lewis, James D.Science (Washington, DC, United States) (2011), 334 (6052), 105-108CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)Diet strongly affects human health, partly by modulating gut microbiome compn. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly assocd. with long-term diets, particularly protein and animal fat (Bacteroides) vs. carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome compn. changed detectably within 24 h of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are assocd. with long-term diet.
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453Akkasheh, G.; Kashani-Poor, Z.; Tajabadi-Ebrahimi, M.; Jafari, P.; Akbari, H.; Taghizadeh, M.; Memarzadeh, M. R.; Asemi, Z.; Esmaillzadeh, A. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition 2016, 32, 315– 320, DOI: 10.1016/j.nut.2015.09.003453https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitVeit7vO&md5=82bddd5d934e0e3ff75ab0ce7a4315aeClinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trialAkkasheh, Ghodarz; Kashani-Poor, Zahra; Tajabadi-Ebrahimi, Maryam; Jafari, Parvaneh; Akbari, Hossein; Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Asemi, Zatollah; Esmaillzadeh, AhmadNutrition (New York, NY, United States) (2016), 32 (3), 315-320CODEN: NUTRER; ISSN:0899-9007. (Elsevier Inc.)We are aware of no study examg. the effects of probiotic supplementation on symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). The present study was designed to det. the effects of probiotic intake on symptoms of depression and metabolic status in patients with MDD. This randomized, double-blind, placebo-controlled clin. trial included 40 patients with a diagnosis of MDD based on DSM-IV criteria whose age ranged between 20 and 55 y. Patients were randomly allocated into two groups to receive either probiotic supplements (n = 20) or placebo (n = 20) for 8 wk. Probiotic capsule consisted of three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 109 CFU/g), Lactobacillus casei (2 × 109 CFU/g), and Bifidobacterium bifidum (2 × 109 CFU/g). Fasting blood samples were taken at the beginning and end of the trial to quantify the relevant variables. All participants provided three dietary records (two weekdays and one weekend) and three phys. activity records during the intervention. Dietary intake of study participants was not significantly different between the two groups. After 8 wk of intervention, patients who received probiotic supplements had significantly decreased Beck Depression Inventory total scores (-5.7 ± 6.4 vs. -1.5 ± 4.8, P = 0.001) compared with the placebo. In addn., significant decreases in serum insulin levels (-2.3 ± 4.1 vs. 2.6 ± 9.3 μIU/mL, P = 0.03), homeostasis model assessment of insulin resistance (-0.6 ± 1.2 vs. 0.6 ± 2.1, P = 0.03), and serum hs-CRP concns. (-1138.7 ± 2274.9 vs. 188.4 ± 1455.5 ng/mL, P = 0.03) were obsd. after the probiotic supplementation compared with the placebo. Addnl., taking probiotics resulted in a significant rise in plasma total glutathione levels (1.8 ± 83.1 vs. -106.8 ± 190.7 μmol/L, P = 0.02) compared with the placebo. We did not find any significant change in fasting plasma glucose, homeostatic model assessment of beta cell function, quant. insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels. Probiotic administration in patients with MDD for 8 wk had beneficial effects on Beck Depression Inventory, insulin, homeostasis model assessment of insulin resistance, hs-CRP concns., and glutathione concns., but did not influence fasting plasma glucose, homeostatic model assessment of beta cell function, quant. insulin sensitivity check index, lipid profiles, and total antioxidant capacity levels.
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454Wallace, C. J. K.; Milev, R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann. Gen. Psychiatry 2017, 16, 14, DOI: 10.1186/s12991-017-0138-2454https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1czgvVSjtA%253D%253D&md5=3f6e3576cc50f596843b164ec596e6c1The effects of probiotics on depressive symptoms in humans: a systematic reviewWallace Caroline J K; Milev RoumenAnnals of general psychiatry (2017), 16 (), 14 ISSN:1744-859X.BACKGROUND: Patients suffering from depression experience significant mood, anxiety, and cognitive symptoms. Currently, most antidepressants work by altering neurotransmitter activity in the brain to improve these symptoms. However, in the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the "gut-brain axis." Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. The aim of this review is to analyze the current body of research assessing the effects of probiotics, on symptoms of depression in humans. METHODS: A systematic search of five databases was performed and study selection was completed using the preferred reporting items for systematic reviews and meta-analyses process. RESULTS: Ten studies met criteria and were analyzed for effects on mood, anxiety, and cognition. Five studies assessed mood symptoms, seven studies assessed anxiety symptoms, and three studies assessed cognition. The majority of the studies found positive results on all measures of depressive symptoms; however, the strain of probiotic, the dosing, and duration of treatment varied widely and no studies assessed sleep. CONCLUSION: The evidence for probiotics alleviating depressive symptoms is compelling but additional double-blind randomized control trials in clinical populations are warranted to further assess efficacy.
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455Le Morvan de Sequeira, C.; Hengstberger, C.; Enck, P.; Mack, I. Effect of Probiotics on Psychiatric Symptoms and Central Nervous System Functions in Human Health and Disease: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 621, DOI: 10.3390/nu14030621There is no corresponding record for this reference.
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456Hill, C.; Guarner, F.; Reid, G.; Gibson, G. R.; Merenstein, D. J.; Pot, B.; Morelli, L.; Canani, R. B.; Flint, H. J.; Salminen, S. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology 2014, 11, 506– 514, DOI: 10.1038/nrgastro.2014.66456https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cfgs12ktQ%253D%253D&md5=471aa530d7d01da3fe859068ed919d75Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probioticHill Colin; Guarner Francisco; Reid Gregor; Gibson Glenn R; Merenstein Daniel J; Pot Bruno; Morelli Lorenzo; Canani Roberto Berni; Flint Harry J; Salminen Seppo; Calder Philip C; Sanders Mary EllenNature reviews. Gastroenterology & hepatology (2014), 11 (8), 506-14 ISSN:.An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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457Dahiya, D.; Nigam, P. S. Clinical Potential of Microbial Strains, Used in Fermentation for Probiotic Food, Beverages and in Synbiotic Supplements, as Psychobiotics for Cognitive Treatment through Gut-Brain Signaling. Microorganisms 2022, 10, 1687, DOI: 10.3390/microorganisms10091687There is no corresponding record for this reference.
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458Zawistowska-Rojek, A.; Tyski, S. How to Improve Health with Biological Agents-Narrative Review. Nutrients 2022, 14, 1700, DOI: 10.3390/nu14091700458https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xhtlenu7zI&md5=ef05cd49a7506e5a1b3bc5bbc3225625How to Improve Health with Biological Agents-Narrative ReviewZawistowska-Rojek, Anna; Tyski, StefanNutrients (2022), 14 (9), 1700CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. The proper functioning of the human organism is dependent on a no. of factors. The health condition of the organism can be often enhanced through appropriate supplementation, as well as the application of certain biol. agents. Probiotics, i.e., live microorganisms that exert a beneficial effect on the health of the host when administered in adequate amts., are often used in commonly available dietary supplements or functional foods, such as yoghurts. Specific strains of microorganisms, administered in appropriate amts., may find application in the treatment of conditions such as various types of diarrhoea (viral, antibiotic-related, caused by Clostridioides difficile), irritable bowel syndrome, ulcerative colitis, Crohns disease, or allergic disorders. In contrast, live microorganisms capable of exerting influence on the nervous system and mental health through interactions with the gut microbiome are referred to as psychobiotics. Live microbes are often used in combination with prebiotics to form synbiotics, which stimulate growth and/or activate the metab. of the healthy gut microbiome. Prebiotics may serve as a substrate for the growth of probiotic strains or fermn. processes. Compared to prebiotic substances, probiotic microorganisms are more tolerant of environmental conditions, such as oxygenation, pH, or temp. in a given organism. It is also worth emphasizing that the health of the host may be influenced not only by live microorganisms, but also by their metabolites or cell components, which are referred to as postbiotics and paraprobiotics. This work presents the mechanisms of action employed by probiotics, prebiotics, synbiotics, postbiotics, paraprobiotics, and psychobiotics, together with the results of studies confirming their effectiveness and impact on consumer health.
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459Gibson, G. R.; Hutkins, R.; Sanders, M. E.; Prescott, S. L.; Reimer, R. A.; Salminen, S. J.; Scott, K.; Stanton, C.; Swanson, K. S.; Cani, P. D. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology 2017, 14, 491– 502, DOI: 10.1038/nrgastro.2017.75459https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1cnotVSjtw%253D%253D&md5=2290a998bde9275fdaa2be7aa7ddad72Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebioticsGibson Glenn R; Hutkins Robert; Sanders Mary Ellen; Prescott Susan L; Reimer Raylene A; Salminen Seppo J; Scott Karen; Stanton Catherine; Swanson Kelly S; Cani Patrice D; Verbeke Kristin; Reid GregorNature reviews. Gastroenterology & hepatology (2017), 14 (8), 491-502 ISSN:.In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.
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460Swanson, K. S.; Gibson, G. R.; Hutkins, R.; Reimer, R. A.; Reid, G.; Verbeke, K.; Scott, K. P.; Holscher, H. D.; Azad, M. B.; Delzenne, N. M. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nature Reviews Gastroenterology & Hepatology 2020, 17, 687– 701, DOI: 10.1038/s41575-020-0344-2460https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38fosF2gsg%253D%253D&md5=d44b595e57356e2fc8ccfa771dce6b34The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbioticsSwanson Kelly S; Gibson Glenn R; Hutkins Robert; Reimer Raylene A; Reid Gregor; Verbeke Kristin; Verbeke Kristin; Scott Karen P; Holscher Hannah D; Azad Meghan B; Delzenne Nathalie M; Sanders Mary EllenNature reviews. Gastroenterology & hepatology (2020), 17 (11), 687-701 ISSN:.In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host". The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.
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461Salminen, S.; Collado, M. C.; Endo, A.; Hill, C.; Lebeer, S.; Quigley, E. M. M.; Sanders, M. E.; Shamir, R.; Swann, J. R.; Szajewska, H. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology 2021, 18, 649– 667, DOI: 10.1038/s41575-021-00440-6461https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c%252FgtlWlsA%253D%253D&md5=76d676b987bba5600ef08a2268b98b73The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbioticsSalminen Seppo; Collado Maria Carmen; Endo Akihito; Hill Colin; Hill Colin; Lebeer Sarah; Quigley Eamonn M M; Sanders Mary Ellen; Shamir Raanan; Shamir Raanan; Swann Jonathan R; Swann Jonathan R; Szajewska Hania; Vinderola GabrielNature reviews. Gastroenterology & hepatology (2021), 18 (9), 649-667 ISSN:.In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term 'postbiotics' is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products.
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462Sarkar, A.; Lehto, S. M.; Harty, S.; Dinan, T. G.; Cryan, J. F.; Burnet, P. W. J. Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals. Trends Neurosci. 2016, 39, 763– 781, DOI: 10.1016/j.tins.2016.09.002462https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhslels7fI&md5=2b8196a74542b35e478de6c67784cf93Psychobiotics and the Manipulation of Bacteria-Gut-Brain SignalsSarkar, Amar; Lehto, Soili M.; Harty, Siobhan; Dinan, Timothy G.; Cryan, John F.; Burnet, Philip W. J.Trends in Neurosciences (2016), 39 (11), 763-781CODEN: TNSCDR; ISSN:0166-2236. (Elsevier Ltd.)Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut-brain signalling mechanisms enabling psychobiotic effects, such as metabolite prodn. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.
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463Long-Smith, C.; O’Riordan, K. J.; Clarke, G.; Stanton, C.; Dinan, T. G.; Cryan, J. F. Microbiota-Gut-Brain Axis: New Therapeutic Opportunities. Annu. Rev. Pharmacol Toxicol 2020, 60, 477– 502, DOI: 10.1146/annurev-pharmtox-010919-023628463https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhslCgu7nJ&md5=65468af6e88f3e9beda5f7da23a715edMicrobiota-Gut-Brain Axis: New Therapeutic OpportunitiesLong-Smith, Caitriona; O'Riordan, Kenneth J.; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.Annual Review of Pharmacology and Toxicology (2020), 60 (), 477-502CODEN: ARPTDI; ISSN:0362-1642. (Annual Reviews)The traditional fields of pharmacol. and toxicol. are beginning to consider the substantial impact our gut microbiota has on host physiol. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addn. to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochem. signaling, direct enteric nervous system routes and the vagus nerve, and the prodn. of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurol. disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clin. management of brain disorders.
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464Pferschy-Wenzig, E. M.; Pausan, M. R.; Ardjomand-Woelkart, K.; Röck, S.; Ammar, R. M.; Kelber, O.; Moissl-Eichinger, C.; Bauer, R. Medicinal Plants and Their Impact on the Gut Microbiome in Mental Health: A Systematic Review. Nutrients 2022, 14, 2111, DOI: 10.3390/nu14102111464https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsVCqsr7F&md5=16c71833085699501bb0bea9aa7e0573Medicinal Plants and Their Impact on the Gut Microbiome in Mental Health: A Systematic ReviewPferschy-Wenzig, Eva-Maria; Pausan, Manuela R.; Ardjomand-Woelkart, Karin; Roeck, Stefanie; Ammar, Ramy M.; Kelber, Olaf; Moissl-Eichinger, Christine; Bauer, RudolfNutrients (2022), 14 (10), 2111CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Various neurocognitive and mental health-related conditions have been assocd. with the gut microbiome, implicating a microbiome-gut-brain axis (MGBA). The aim of this systematic review was to identify, categorize, and review clin. evidence supporting medicinal plants for the treatment of mental disorders and studies on their interactions with the gut microbiota. This review included medicinal plants for which clin. studies on depression, sleeping disorders, anxiety, or cognitive dysfunction as well as scientific evidence of interaction with the gut microbiome were available. The studies were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Eighty-five studies met the inclusion criteria and covered thirty mental health-related medicinal plants with data on interaction with the gut microbiome. Only a few studies have been specifically designed to assess how herbal prepns. affect MGBA-related targets or pathways. However, many studies provide hints of a possible interaction with the MGBA, such as an increased abundance of health-beneficial microorganisms, anti-inflammatory effects, or MGBA-related pathway effects by gut microbial metabolites. Data for Panax ginseng, Schisandra chinensis, and Salvia rosmarinus indicate that the interaction of their constituents with the gut microbiota could mediate mental health benefits. Studies specifically assessing the effects on MGBA-related pathways are still required for most medicinal plants.
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465PitchBook. https://www.pitchbook.com/ (accessed March 30, 2023).There is no corresponding record for this reference.
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466Black, C. J.; Ford, A. C. Global burden of irritable bowel syndrome: trends, predictions and risk factors. Nature Reviews Gastroenterology & Hepatology 2020, 17, 473– 486, DOI: 10.1038/s41575-020-0286-8466https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zlvVSnsQ%253D%253D&md5=f3bdedacf74908abb87ab505df660d03Global burden of irritable bowel syndrome: trends, predictions and risk factorsBlack Christopher J; Ford Alexander C; Black Christopher J; Ford Alexander CNature reviews. Gastroenterology & hepatology (2020), 17 (8), 473-486 ISSN:.Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction worldwide, defined according to patterns of gastrointestinal symptoms as described by the Rome diagnostic criteria. However, these criteria, developed with reference to research conducted largely in Western populations, might be limited in their applicability to other countries and cultures. Epidemiological data show a wide variation in the prevalence of IBS globally and more rigorous studies are needed to accurately determine any differences that might exist between countries as well as the potential explanations. The effects of IBS on the individual, in terms of their quality of life, and on health-care delivery and society, in terms of economic costs, are considerable. Although the magnitude of these effects seems to be comparable between nations, their precise nature can vary based on the existence of societal and cultural differences. The pathophysiology of IBS is complex and incompletely understood; genetics, diet and the gut microbiome are all recognized risk factors, but the part they play might be influenced by geography and culture, and hence their relative importance might vary between countries. This Review aims to provide an overview of the burden of IBS in a global context, to discuss future implications for the care of people with IBS worldwide, and to identify key areas for further research.
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467Fecal Microbiota Transplantation. https://www.idsociety.org/public-health/emerging-clinical-issues/emerging-clinical-issues/fecal-microbiota-transplantation/ (accessed November 28, 2022).There is no corresponding record for this reference.
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468BiomeBank announces world first regulatory approval for donor derived microbiome drug. https://www.biomebank.com/news/media-release/biomebank-announces-world-first-regulatory-approval-for-donor-derived-microbiome-drug/ (accessed November 22, 2022).There is no corresponding record for this reference.
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469Ferring Receives U.S. FDA Approval for REBYOTA (fecal microbiota, live-jslm) – A Novel First-in-Class Microbiota-Based Live Biotherapeutic. https://ferringusa.com/?press=ferring-receives-u-s-fda-approval-for-rebyota-fecal-microbiota-live-jslm-a-novel-first-in-class-microbiota-based-live-biotherapeutic (accessed December 6, 2022).There is no corresponding record for this reference.
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470Clinical Trials. https://www.clinicaltrials.gov/ (accessed January 27, 2023).There is no corresponding record for this reference.
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471Fijan, S. Microorganisms with claimed probiotic properties: an overview of recent literature. Int. J. Environ. Res. Public Health 2014, 11, 4745– 4767, DOI: 10.3390/ijerph110504745471https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cjmt1CjsQ%253D%253D&md5=665bec4cd83ddfc93d8208a5f212d019Microorganisms with claimed probiotic properties: an overview of recent literatureFijan SabinaInternational journal of environmental research and public health (2014), 11 (5), 4745-67 ISSN:.Probiotics are defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. Health benefits have mainly been demonstrated for specific probiotic strains of the following genera: Lactobacillus, Bifidobacterium, Saccharomyces, Enterococcus, Streptococcus, Pediococcus, Leuconostoc, Bacillus, Escherichia coli. The human microbiota is getting a lot of attention today and research has already demonstrated that alteration of this microbiota may have far-reaching consequences. One of the possible routes for correcting dysbiosis is by consuming probiotics. The credibility of specific health claims of probiotics and their safety must be established through science-based clinical studies. This overview summarizes the most commonly used probiotic microorganisms and their demonstrated health claims. As probiotic properties have been shown to be strain specific, accurate identification of particular strains is also very important. On the other hand, it is also demonstrated that the use of various probiotics for immunocompromised patients or patients with a leaky gut has also yielded infections, sepsis, fungemia, bacteraemia. Although the vast majority of probiotics that are used today are generally regarded as safe and beneficial for healthy individuals, caution in selecting and monitoring of probiotics for patients is needed and complete consideration of risk-benefit ratio before prescribing is recommended.
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472Effect of Two Probiotic Formulations on Mental Health and Mood Biomarkers in Adults With Depressive Symptoms. https://clinicaltrials.gov/ct2/show/NCT05564767?term=NCT05564767&draw=2&rank=1 (accessed November 27, 2022).There is no corresponding record for this reference.
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473Effects of Probiotics on Gut Microbiota, Endocannabinoid and Immune Activation and Symptoms of Fatigue in Dancers. https://clinicaltrials.gov/ct2/show/NCT05567653?term=NCT05567653&draw=2&rank=1 (accessed November 27, 2022).There is no corresponding record for this reference.
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474Probiotics on Sleep Among Adults Study. https://clinicaltrials.gov/ct2/show/NCT04767997?term=NCT04767997&draw=2&rank=1 (accessed November 27, 2022).There is no corresponding record for this reference.
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475Rode, J.; Edebol Carlman, H. M. T.; König, J.; Repsilber, D.; Hutchinson, A. N.; Thunberg, P.; Andersson, P.; Persson, J.; Kiselev, A.; Lathrop Stern, L. Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial. Front Nutr 2022, 9, 827182, DOI: 10.3389/fnut.2022.827182475https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2Mnit1Oktg%253D%253D&md5=992d10e4fde63393ce50a0df69755f33Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical TrialRode Julia; Edebol Carlman Hanna M T; Konig Julia; Repsilber Dirk; Hutchinson Ashley N; Salomon Benita; Brummer Robert J; Thunberg Per; Mohammed Ahmed Abdulilah; Andersson Pernilla; Persson Jonas; Kiselev Andrey; Lathrop Stern Lori; Labus Jennifer SFrontiers in nutrition (2022), 9 (), 827182 ISSN:2296-861X.Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited. Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 10(9) CFU/day) affected functional brain responses in healthy subjects during an emotional attention task. Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed. Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention. Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest. Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].
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476Patterson, E.; Griffin, S. M.; Ibarra, A.; Ellsiepen, E.; Hellhammer, J. Lacticaseibacillus paracasei Lpc-37® improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study). Neurobiol Stress 2020, 13, 100277, DOI: 10.1016/j.ynstr.2020.100277476https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XitVWgsLvF&md5=88dbb2663f829cffce4519fe835e874eLacticaseibacillus paracasei Lpc-37 improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study)Patterson, Elaine; Griffin, Sile M.; Ibarra, Alvin; Ellsiepen, Emilia; Hellhammer, JulianeNeurobiology of Stress (2020), 13 (), 100277CODEN: NSETCA; ISSN:2352-2895. (Elsevier Inc.)Chronic stress is a risk-factor for the development of mood and stress-related disorders. Clin. evidence indicates that probiotics can influence the stress response and mood. The Sisu study investigated whether Lacticaseibacillus paracasei Lpc-37 (Lpc-37) could modulate stress, mood and well-being. Prior to a two-week run-in period, 120 healthy adults (18-45 y) were stratified for sex and chronic stress and randomized to either 1.75 x 1010 colony forming units (CFU) of Lpc-37 or placebo (1:1) per day for 5 wk. The primary objective was the effect of Lpc-37 on heart rate (HR) in response to the Trier Social Stress Test (TSST). Secondary objectives were assessed by biomarkers and self-report scales over the study. The primary hypothesis was not met in either the Intention-to-Treat (ITT) or Per Protocol (PP) population, but Lpc-37 reduced the increase in HR in participants with low chronic stress (LCS) and increased HR in participants with high chronic stress (HCS) during the TSST. Supporting significant efficacy in the PP population (n = 113), Lpc-37 reduced perceived stress following intervention. More significant effects were identified within the subgroups where Lpc-37 reduced exhaustion during the TSST and normalized cortisol levels at 8pm in participants with LCS, reduced perceived stress also in females, and increased perceived health and sleep-related recovery in participants with HCS. Adverse events (AEs) were similar between groups, there were no severe AEs, and vital signs remained unchanged. Overall, Lpc-37 reduced perceived stress compared to placebo. Other beneficial effects within biomarkers related to stress indicate that the effects of Lpc-37 may be differentially dependent on sex and chronic stress. (ClinicalTrials.gov: NCT03494725).
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477Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects. https://www.clinicaltrials.gov/ct2/show/NCT03494725?term=NCT03494725&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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478The Cognitive Effects of 6 Weeks Administration With a Probiotic. https://www.clinicaltrials.gov/ct2/show/NCT03601559?term=NCT03601559&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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479Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects. https://www.clinicaltrials.gov/ct2/show/NCT03615651?term=NCT03615651&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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480Lactobacillus Plantarum DR7 for Gut-Brain-Axis Benefits (DR7). https://www.clinicaltrials.gov/ct2/show/NCT03370458?term=NCT03370458&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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481Sur, D.; Manna, B.; Niyogi, S. K.; Ramamurthy, T.; Palit, A.; Nomoto, K.; Takahashi, T.; Shima, T.; Tsuji, H.; Kurakawa, T. Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized, double-blind placebo-controlled field trial in an urban slum. Epidemiology and Infection 2011, 139, 919– 926, DOI: 10.1017/S0950268810001780481https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3MvmtlWktw%253D%253D&md5=18d9556544808794f0dc81193a23d533Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized, double-blind placebo-controlled field trial in an urban slumSur D; Manna B; Niyogi S K; Ramamurthy T; Palit A; Nomoto K; Takahashi T; Shima T; Tsuji H; Kurakawa T; Takeda Y; Nair G B; Bhattacharya S KEpidemiology and infection (2011), 139 (6), 919-26 ISSN:.Acute diarrhoea remains a major public health challenge in developing countries. We examined the role of a probiotic in the prevention of acute diarrhoea to discover if there was an effect directed towards a specific aetiology. A double-blind, randomized, controlled field trial involving 3758 children aged 1-5 years was conducted in an urban slum community in Kolkata, India. Participants were given either a probiotic drink containing Lactobacillus casei strain Shirota or a nutrient drink daily for 12 weeks. They were followed up for another 12 weeks. The primary outcome of this study was the occurrence of first episodes of diarrhoea. We assessed this during 12 weeks of intake of study agent and also for 12 weeks of follow-up. There were 608 subjects with diarrhoea in the probiotic group and 674 subjects in the nutrient group during the study period of 24 weeks. The level of protective efficacy for the probiotic was 14% (95% confidence interval 4-23, P<0·01 in adjusted model). The reduced occurrence of acute diarrhoea in the probiotic group compared to nutrient group was not associated with any specific aetiology. No adverse event was observed in children of either probiotic or nutrient groups. The study suggests that daily intake of a probiotic drink can play a role in prevention of acute diarrhoea in young children in a community setting of a developing country.
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482Cottrell, J.; Koenig, K.; Perfekt, R.; Hofmann, R.; For the Loperamide–Simethicone Acute Diarrhoea Study, T. Comparison of Two Forms of Loperamide–Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial. Drugs R&D 2015, 15, 363– 373, DOI: 10.1007/s40268-015-0111-yThere is no corresponding record for this reference.
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483Skrzydło-Radomańska, B.; Prozorow-Król, B.; Cichoż-Lach, H.; Majsiak, E.; Bierła, J. B.; Kanarek, E.; Sowińska, A.; Cukrowska, B. The Effectiveness and Safety of Multi-Strain Probiotic Preparation in Patients with Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Controlled Study. Nutrients 2021, 13, 756, DOI: 10.3390/nu13030756483https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtFGisrrO&md5=daf5ccef30be66efaa9941a085951d88The effectiveness and safety of multi-strain probiotic preparation in patients with diarrhea-predominant irritable bowel syndrome: a randomized controlled studySkrzydlo-Radomanska, Barbara; Prozorow-Krol, Beata; Cichoz-Lach, Halina; Majsiak, Emilia; Bierla, Joanna Beata; Kanarek, Ewelina; Sowinska, Agnieszka; Cukrowska, BozenaNutrients (2021), 13 (3), 756CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)The aim of this randomized double-blind placebo-controlled study was to evaluate the effectiveness and safety of multi-strain probiotic in adults with diarrhea-predominant irritable bowel syndrome (IBS-D). The patients were randomized to receive a mixt. of Lactobacillus, Bifidobacterium, and Streptococcus thermophilus strains or placebo for eight weeks. Primary endpoints included changes in symptom severity and improvement assessed with the IBS Severity Scoring System (IBS-SSS) and Global Improvement Scale (IBS-GIS). The probiotic in comparison with placebo significantly improved the IBS symptom severity (the change of total IBS-SSS score from baseline -165.8 ± 78.9 in the probiotic group and -105.6 ± 60.2 in the placebo group, p = 0.005) and in the specific scores related to the severity of pain (p = 0.015) and the quality of life (p = 0.016) after eight weeks of intervention. The probiotic group indicated an improvement in symptoms with the use of the IBS-GIS compared with the placebo group after four (p = 0.04) and eight weeks (p = 0.003). The occurrence of adverse events did not differ between study groups. In conclusion, the multi-strain probiotic intervention resulted in a significant improvement in IBS symptoms evaluated with the use of both IBS-SSS and IBS-GIS scales. The results suggest that the studied probiotic prepn. is well tolerated and safe and can offer benefits for patients with IBS-D. (registration no. in Clinicaltrials.gov NCT 04662957).
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484Quigley, E. M. M.; Markinson, L.; Stevenson, A.; Treasure, F. P.; Lacy, B. E. Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome. Aliment. Pharmacol. Ther. 2023, 57, 81– 93, DOI: 10.1111/apt.17310484https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFalsLfF&md5=9d42fc333ad4607a2a0d0a361274ae6fRandomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndromeQuigley, Eamonn M. M.; Markinson, Louise; Stevenson, Alex; Treasure, F. Peter; Lacy, Brian E.Alimentary Pharmacology and Therapeutics (2023), 57 (1), 81-93CODEN: APTHEN; ISSN:0269-2813. (Wiley-Blackwell)MRx1234 is a live biotherapeutic product that contains a strain of Blautia hydrogenotrophica. It is in development for the treatment of irritable bowel syndrome (IBS). To assess the efficacy and safety of MRx1234 in patients with IBS with predominant constipation (IBS-C) or diarrhoea (IBS-D) Methods : We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients aged 18-70 years in two parallel cohorts (IBS-C; IBS-D) were randomised (1:1) to MRx1234 or placebo for 8 wk. The primary efficacy endpoint was overall responder rate-a composite of improved bowel habit (IBS-C: stool frequency; IBS-D: stool consistency) and abdominal pain intensity-for ≥50% of the treatment period in each cohort. Statistical testing was at a one-sided 0.10 significance level. Of 366 randomised patients (164 IBS-C; 202 IBS-D), 365 received any study medication (177 MRx1234, 188 placebo). Numerically, although not statistically significantly different, more patients who received MRx1234 than placebo were overall responders in the IBS-C (25.0% vs. 17.1%) and IBS-D (23.4% vs. 17.8%) cohorts. Similar results were obsd. in the addnl. combined cohort anal. (24.1% vs. 17.5%; p = 0.063). For the components of the primary endpoint, significantly more patients on MRx1234 than placebo reported improvement in bowel habit in the IBS-C, IBS-D and combined cohorts, while improvements in abdominal pain were obsd. in each cohort. The safety profile of MRx1234 was similar to placebo. MRx1234 has the potential to become a novel, safe treatment option for patients with IBS-C or IBS-D, and for those who have mixed symptoms or transition between subtypes. #NCT03721107.
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485Effect of Lactobacillus Gasseri DSM 27123 on Functional Constipation in Healthy Women. https://www.clinicaltrials.gov/ct2/show/NCT02592200?term=NCT02592200&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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486Dietary Supplementation Effects on Bowel Movement Frequency and Intestinal Biological Markers in Seniors Presenting Slowed Intestinal Transit. https://www.clinicaltrials.gov/ct2/show/NCT04304170?term=NCT04304170&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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487Multi Strain Probiotic Preparation in Patients With Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT04662957?term=NCT04662957&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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488The Effect of Probiotic Supported Yogurt Consumption on Gastrointestinal Symptoms. https://www.clinicaltrials.gov/ct2/show/NCT05566171?term=NCT05566171&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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489B. Lactis HN019 for Functional Constipation (CTT). https://www.clinicaltrials.gov/ct2/show/NCT01463293?term=NCT01463293&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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490Effects of Cultura Yoghurt in Relation to Transit Time and Digestive Discomfort in Healthy Women and Men. https://www.clinicaltrials.gov/ct2/show/NCT01102036?term=NCT01102036&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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491A Trial for New Treatment of Adult Participants With Irritable Bowel Syndrome. https://clinicaltrials.gov/ct2/show/NCT03721107?term=NCT03721107&draw=2&rank=1 (accessed Feb 16, 2023).There is no corresponding record for this reference.
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492Randomized Controlled Field Trial of a Probiotics to Assess Its Role in Preventig Diarrhoea (Yakult). https://www.clinicaltrials.gov/ct2/show/NCT00534170?term=NCT00534170&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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493Probiotics and Hospital Outcome in the Elderly (PROAGE). https://www.clinicaltrials.gov/ct2/show/NCT00794924?term=NCT00794924&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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494Evaluation of the Efficacy of Two Probiotic Strains for Irritable Bowel Syndrome (14PIHL). https://www.clinicaltrials.gov/ct2/show/NCT02213172?term=NCT02213172&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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495A Comparison of Three Medications to Treat Diarrhea in Adults. https://www.clinicaltrials.gov/ct2/show/NCT00807326?term=NCT00807326&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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496A Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT05054309?term=NCT05054309&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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497Study to Evaluate a Probiotic in Healthy Subjects With a History of Abdominal Discomfort and Bloating. https://www.clinicaltrials.gov/ct2/show/NCT01099696?term=NCT01099696&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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498Efficacy of a Multi-strain Probiotic in the Treatment of Irritable Bowel Syndrome (IBS). https://www.clinicaltrials.gov/ct2/show/NCT01887834?term=NCT01887834&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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499Trial to Evaluate Dietary Supplements to Maintain Gut Health During Travel (P3). https://www.clinicaltrials.gov/ct2/show/NCT04605783?term=NCT04605783&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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500To Study the Efficacy and Safety of L. Plantarum UALp-05TM in Diarrhea- Predominant-irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT04950296?term=NCT04950296&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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501Saccharomyces Cerevisiae for Irritable Bowel Syndrome (IBS). https://www.clinicaltrials.gov/ct2/show/NCT05149599?term=NCT05149599&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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502Johnstone, N.; Milesi, C.; Burn, O.; van den Bogert, B.; Nauta, A.; Hart, K.; Sowden, P.; Burnet, P. W. J.; Cohen Kadosh, K. Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18–25 years) with corresponding changes in gut bacterial composition. Sci. Rep. 2021, 11, 8302, DOI: 10.1038/s41598-021-87865-w502https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXpt1Wkurk%253D&md5=46c02b64c8e170d6225768d3f2d3ef4eAnxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18-25 years) with corresponding changes in gut bacterial compositionJohnstone, Nicola; Milesi, Chiara; Burn, Olivia; van den Bogert, Bartholomeus; Nauta, Arjen; Hart, Kathryn; Sowden, Paul; Burnet, Philip W. J.; Cohen Kadosh, KathrinScientific Reports (2021), 11 (1), 8302CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)Current research implicates pre- and probiotic supplementation as a potential tool for improving symptomol. in phys. and mental ailments, which makes it an attractive concept for clinicians and consumers alike. Here we focus on the transitional period of late adolescence and early adulthood during which effective interventions, such as nutritional supplementation to influence the gut microbiota, have the potential to offset health-related costs in later life. We examd. multiple indexes of mood and well-being in 64 healthy females in a 4-wk double blind, placebo controlled galacto-oligosaccharides (GOS) prebiotic supplement intervention and obtained stool samples at baseline and follow-up for gut microbiota sequencing and analyses. We report effects of the GOS intervention on self-reported high trait anxiety, attentional bias, and bacterial abundance, suggesting that dietary supplementation with a GOS prebiotic may improve indexes of pre-clin. anxiety. Gut microbiota research has captured the imagination of the scientific and lay community alike, yet we are now at a stage where this early enthusiasm will need to be met with rigorous research in humans. Our work makes an important contribution to this effort by combining a psychobiotic intervention in a human sample with comprehensive behavioral and gut microbiota measures.
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503Parilli-Moser, I.; Domínguez-López, I.; Trius-Soler, M.; Castellví, M.; Bosch, B.; Castro-Barquero, S.; Estruch, R.; Hurtado-Barroso, S.; Lamuela-Raventós, R. M. Consumption of peanut products improves memory and stress response in healthy adults from the ARISTOTLE study: A 6-month randomized controlled trial. Clin. Nutr. 2021, 40, 5556– 5567, DOI: 10.1016/j.clnu.2021.09.020503https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitlantbjF&md5=2adc0ba0d3a56ab9ccd080ea8288c72eConsumption of peanut products improves memory and stress response in healthy adults from the ARISTOTLE study: A 6-month randomized controlled trialParilli-Moser, Isabella; Dominguez-Lopez, Ines; Trius-Soler, Marta; Castellvi, Magda; Bosch, Beatriz; Castro-Barquero, Sara; Estruch, Ramon; Hurtado-Barroso, Sara; Lamuela-Raventos, Rosa M.Clinical Nutrition (2021), 40 (11), 5556-5567CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)Peanuts are rich in bioactive compds. that may have a pos. impact on memory and stress response.To evaluate the effect of regular consumption of peanut products on cognitive functions and stress response in healthy young adults.A three-arm parallel-group randomized controlled trial was conducted in 63 healthy young adults that consumed 25 g/day of skin roasted peanuts (SRP, n = 21), 32 g/d of peanut butter (PB, n = 23) or 32 g/d of a control butter made from peanut oil (free of phenolic compds. and fiber) (CB, n = 19) for six months. Polyphenol intake, cognitive functions, and anxiety and depression scores were evaluated using validated tests. Fecal short-chain fatty acids (SCFAs) and plasma and fecal fatty acids were assessed by chromatog. methods. Urinary cortisol was quantified by an enzymic method.Comparing the two interventions with the control, a significant redn. in anxiety scores was obsd. in the SRP compared to the CB group. After the intervention, consumers of SRP and PB had an improved immediate memory (p = 0.046 and p = 0.011). Lower anxiety scores were assocd. with SRP and PB (p < 0.001 and p = 0.002, resp.) and lower depression scores with SRP, PB and CB (p = 0.007, p = 0.003 and p = 0.032, resp.). Memory functions and stress response were significantly correlated with polyphenol intake, fecal SCFAs, plasma and fecal very long chain satd. fatty acids (VLCSFAs).Regular peanut and peanut butter consumption may enhance memory function and stress response in a healthy young population. These effects seem to be assocd. with the intake of peanut polyphenols, increased levels of fecal SCFAs, and unexpectedly, VLCSFAs, which were also present in the control product.
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504Prebiotics and Stress Reduction in Women. https://www.clinicaltrials.gov/ct2/show/NCT05372601?term=NCT05372601&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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505Evaluating the Effects of Prebiotics on Sleep, the Gut Microbiome, Cognition, Immune Function and Stress. https://www.clinicaltrials.gov/ct2/show/NCT05239845?term=NCT05239845&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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506Healthy Prebiotic and Postbiotic Effects of Peanuts and Peanut Butter: College Intervention Trial (ARISTOTLE). https://www.clinicaltrials.gov/ct2/show/NCT04324749?term=NCT04324749&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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507Polyphenols, Prebiotics, the Gut Microbiome and Stress. https://www.clinicaltrials.gov/ct2/show/NCT05528575?term=NCT05528575&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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508Prebiotics and Mental Health: Behavioural. https://www.clinicaltrials.gov/ct2/show/NCT04616937?term=NCT04616937&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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509Selling, J.; Swann, P.; Madsen, L. R., 2nd; Oswald, J. Improvement in Gastroesophageal Reflux Symptoms From a Food-grade Maltosyl-isomaltooligosaccharide Soluble Fiber Supplement: A Case Series. Integr. Med. 2018, 17, 40– 42509https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3M7htlShtw%253D%253D&md5=8cc979543313d4e4486c5c9d55ceb387Improvement in Gastroesophageal Reflux Symptoms From a Food-grade Maltosyl-isomaltooligosaccharide Soluble Fiber Supplement: A Case SeriesSelling John; Swann Peter; Madsen Lee R 2nd; Oswald JackIntegrative medicine (Encinitas, Calif.) (2018), 17 (5), 40-42 ISSN:1546-993X.Gastroesophageal reflux disease (GERD) is a very common medical condition. Symptom improvement from ingested prebiotic soluble fiber has not been reported previously. In fact, a related soluble fiber, fructooligosaccharides, has been shown to worsen GERD. We report on a series of 24 patients with GERD, 88% of which improved after several weeks of daily consumption of a specific maltosyl-isomaltooligosaccharide (MIMO) fermented prebiotic soluble fiber. We also report on 2 proton pump inhibitor (PPI)-dependent patients with GERD who, after beginning daily MIMO, were able to eliminate PPI therapy. The hypotheses explaining the mechanism for GERD improvement with MIMO is discussed. To the best of our knowledge, these cases are the first time any prebiotic soluble fiber has been reported to improve or eliminate symptoms of GERD and enable patients with GERD to decrease or eliminate their PPI therapy.
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510Ansell, J.; Butts, C. A.; Paturi, G.; Eady, S. L.; Wallace, A. J.; Hedderley, D.; Gearry, R. B. Kiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled study. Nutr. Res. (N.Y.) 2015, 35, 401– 408, DOI: 10.1016/j.nutres.2015.04.005510https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnt1ersb4%253D&md5=a18d0435a7b48f860f0215c05b43775aKiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled studyAnsell, Juliet; Butts, Christine A.; Paturi, Gunaranjan; Eady, Sarah L.; Wallace, Alison J.; Hedderley, Duncan; Gearry, Richard B.Nutrition Research (New York, NY, United States) (2015), 35 (5), 401-408CODEN: NTRSDC; ISSN:0271-5317. (Elsevier)The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, double-blind, placebo-controlled study, we examd. the effects of Actazin and Gold, kiwifruit-derived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14-day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were obsd. in stool form as detd. by use of the Bristol stool scale. In a subgroup anal. of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the no. of daily bowel movements by greater than 1 bowel movement per wk. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup anal. of responders. This study demonstrated that Actazin and Gold produced clin. meaningful increases in bowel movements in healthy individuals.
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511Blatchford, P.; Stoklosinski, H.; Eady, S.; Wallace, A.; Butts, C.; Gearry, R.; Gibson, G.; Ansell, J. Consumption of kiwifruit capsules increases Faecalibacterium prausnitzii abundance in functionally constipated individuals: a randomised controlled human trial. J. Nutr Sci. 2017, 6, e52, DOI: 10.1017/jns.2017.52511https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXls12gu7g%253D&md5=dc4a812ca413cc495e808a9e192fe605Consumption of kiwifruit capsules increases Faecalibacterium prausnitziiabundance in functionally constipated individuals: a randomised controlledhuman trialBlatchford, Paul; Stoklosinski, Halina; Eady, Sarah; Wallace, Alison; Butts, Christine; Gearry, Richard; Gibson, Glenn; Ansell, JulietJournal of Nutritional Science (2017), 6 (), e52/1-e52/10CODEN: JNSOAI; ISSN:2048-6790. (Cambridge University Press)This study investigated the impact of ACTAZINTM green (2400 and 600 mg) and LivauxTM (2400 mg) gold kiwifruit supplements on faecal microbial compn. and metabolites in healthy and functionally constipated (FC) participants. The participants were recruited into the healthy group (n 20; one of whom did not complete the study) and the FC group (n 9), each of whom consumed all the treatments and a placebo (isomalt) for 4 wk in a randomised cross-over design interspersed with 2-wk washout periods. Modiflcation of faecal microbiota compn. and metab. was detd. by 16S rRNA gene sequencing and GC, and colonic pH was calcd. using SmartPill wireless motility capsules. A total of thirty-two taxa were measured at greater than 1% abundance in at least one sample, ten of which differed signiflcantly between the baseline healthy and FC groups. Speciflcally, Bacteroidales and Roseburia spp. were signiflcantly more abundant (P < 0.05) in the healthy group and taxa including Ruminococcaceae, Dorea spp. and Akkermansia spp. were signiflcantly more abundant (P < 0.05) in the FC group. In the FC group, Faecalibacterium prausnitzii abundance signiflcantly increased (P = 0.024) from 3.4 to 7.0% following LivauxTM supplementation, with eight of the nine participants showing a net increase. Lower proportions of F. prausnitzii are often assocd. with gastrointestinal disorders. The discovery that LivauxTM supplementation increased F. prausnitzii abundance offers a potential strategy for improving gut microbiota compn., as F. prausnitzii is a butyrate producer and has also been shown to exert anti-inflammatory effects in many studies.
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512SILK, D. B. A.; DAVIS, A.; VULEVIC, J.; TZORTZIS, G.; GIBSON, G. R. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment. Pharmacol. Ther. 2009, 29, 508– 518, DOI: 10.1111/j.1365-2036.2008.03911.x512https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjslaltbg%253D&md5=09dbece5e9a12382749ee12439f7ace8Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndromeSilk, D. B. A.; Davis, A.; Vulevic, J.; Tzortzis, G.; Gibson, G. R.Alimentary Pharmacology and Therapeutics (2009), 29 (5), 508-518CODEN: APTHEN; ISSN:0269-2813. (Wiley-Blackwell)Background: Gut microflora-mucosal interactions may be involved in the pathogenesis of irritable bowel syndrome (IBS). Aim: To investigate the efficacy of a novel prebiotic trans-galactooligosaccharide in changing the colonic microflora and improve the symptoms in IBS sufferers. Methods: In all, 44 patients with Rome II pos. IBS completed a 12-wk single center parallel crossover controlled clin. trial. Patients were randomized to receive either 3.5 g/d prebiotic, 7 g/d prebiotic or 7 g/d placebo. IBS symptoms were monitored weekly and scored according to a 7-point Likert scale. Changes in faecal microflora, stool frequency and form (Bristol stool scale) subjective global assessment (SGA), anxiety and depression and QOL scores were also monitored. Results: The prebiotic significantly enhanced faecal bifidobacteria (3.5 g/d P < 0.005; 7 g/d P < 0.001). Placebo was without effect on the clin. parameters monitored, while the prebiotic at 3.5 g/d significantly changed stool consistency (P < 0.05), improved flatulence (P < 0.05) bloating (P < 0.05), composite score of symptoms (P < 0.05) and SGA (P < 0.05). The prebiotic at 7 g/d significantly improved SGA (P < 0.05) and anxiety scores (P < 0.05). Conclusion: The galactooligosaccharide acted as a prebiotic in specifically stimulating gut bifidobacteria in IBS patients and is effective in alleviating symptoms. These findings suggest that the prebiotic has potential as a therapeutic agent in IBS.
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513Tolerability Study of a Novel Microbiome Therapeutic in Subjects With Gastroesophageal Reflux Disease. https://www.clinicaltrials.gov/ct2/show/NCT04491734?term=NCT04491734&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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514Utility of the Administration of Chesnut and Quebracho Extract for Irritable Bowel Syndrome Diarrhea Predominant. https://www.clinicaltrials.gov/ct2/show/NCT05207618?term=NCT05207618&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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515Evaluation of the Efficacy of a New Specific Infant Formula in Case of Functional Constipation. https://www.clinicaltrials.gov/ct2/show/NCT05340712?term=NCT05340712&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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516ReFerm. https://referm.dk/ (accessed November 27, 2022).There is no corresponding record for this reference.
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517Effect of Postbiotic Product on Colonic Barriers in IBS. https://www.clinicaltrials.gov/ct2/show/NCT05475314?term=NCT05475314&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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518Pilot Study to Assess the Effect of a Postbiotic Blend on Moderate Self-reported Anxiety (Anx). https://www.clinicaltrials.gov/ct2/show/NCT05562739?term=NCT05562739&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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519Evaluating the Safety and Efficacy of the Probiotic Bifidobacterium Longum ES1 and the Post Biotic Heat-treated Bifidobacterium Longum ES1 (HT-ES1) on IBS Symptom Severity in Patients With Diarrhoea Predominant Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT05339243?term=NCT05339243&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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520König, J.; Brummer, R. J. Faecal microbiota transplantation in IBS ─ new evidence for success?. Nature Reviews Gastroenterology & Hepatology 2020, 17, 199– 200, DOI: 10.1038/s41575-020-0282-z520https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB387ntVWqtg%253D%253D&md5=e30412f63f904df76eeec7def1975769Faecal microbiota transplantation in IBS - new evidence for success?Konig Julia; Brummer Robert JanNature reviews. Gastroenterology & hepatology (2020), 17 (4), 199-200 ISSN:.There is no expanded citation for this reference.
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521El-Salhy, M.; Winkel, R.; Casen, C.; Hausken, T.; Gilja, O. H.; Hatlebakk, J. G. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology 2022, 163, 982– 994.e14, DOI: 10.1053/j.gastro.2022.06.020521https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2MjmtVejtA%253D%253D&md5=c454e89729d7379ea07f3be3ea52a0e0Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After TransplantationEl-Salhy Magdy; Winkel Renate; Casen Christina; Hausken Trygve; Gilja Odd Helge; Hatlebakk Jan GunnarGastroenterology (2022), 163 (4), 982-994.e14 ISSN:.BACKGROUND & AIMS: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS) are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects. METHODS: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed 5 questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index were analyzed using 16S ribosomal RNA gene polymerase chain reaction DNA amplification/probe hybridization covering the V3 to V9 regions. RESULTS: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The dysbiosis index decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded. CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events. This study was registered at www. CLINICALTRIALS: gov (NCT03822299).
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522Effects of Faecal Microbiota Transplantation in Patients With IBS. https://www.clinicaltrials.gov/ct2/show/NCT03822299?term=NCT03822299&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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523Fecal Microbiota Transplantation in Patients With Irritable Bowel Syndrome. https://www.clinicaltrials.gov/ct2/show/NCT02092402?term=NCT02092402&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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524RCE With FMT in the Treatment of Childhood Constipation. https://www.clinicaltrials.gov/ct2/show/NCT05035784?term=NCT05035784&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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525FMT Capsules in Treatment of Patients With Insomnia Clinical Research. https://www.clinicaltrials.gov/ct2/show/NCT05427331?term=NCT05427331&draw=2&rank=1 (accessed November 28, 2022).There is no corresponding record for this reference.
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526Haridy, R. Australia gives world-first regulatory approval to fecal transplant therapy. https://newatlas.com/medical/first-approval-fecal-transplant-gut-microbiome-therapy/ (accessed November 22, 2022).There is no corresponding record for this reference.
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527Shepherd, T. A coup for poo: why the world’s first faecal transplant approval matters. The Guardian , November 12, 2022. https://www.theguardian.com/australia-news/2022/nov/13/a-coup-for-poo-why-the-worlds-first-faecal-transplant-approval-matters (accessed November 22, 2022).There is no corresponding record for this reference.
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528FDA Approves First Fecal Microbiota Product. https://www.fda.gov/news-events/press-announcements/fda-approves-first-fecal-microbiota-product (accessed December 2, 2022).There is no corresponding record for this reference.
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529Shaffer, J. P.; Nothias, L.-F.; Thompson, L. R.; Sanders, J. G.; Salido, R. A.; Couvillion, S. P.; Brejnrod, A. D.; Lejzerowicz, F.; Haiminen, N.; Huang, S. Standardized multi-omics of Earth’s microbiomes reveals microbial and metabolite diversity. Nat. Microbiol. 2022, 7, 2128, DOI: 10.1038/s41564-022-01266-x529https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivFOlsbrE&md5=6e1699fe35109ff8f4c0ad138a0fb2bfStandardized multi-omics of Earth's microbiomes reveals microbial and metabolite diversityShaffer, Justin P.; Nothias, Louis-Felix; Thompson, Luke R.; Sanders, Jon G.; Salido, Rodolfo A.; Couvillion, Sneha P.; Brejnrod, Asker D.; Lejzerowicz, Franck; Haiminen, Niina; Huang, Shi; Lutz, Holly L.; Zhu, Qiyun; Martino, Cameron; Morton, James T.; Karthikeyan, Smruthi; Nothias-Esposito, Melissa; Duhrkop, Kai; Bocker, Sebastian; Kim, Hyun Woo; Aksenov, Alexander A.; Bittremieux, Wout; Minich, Jeremiah J.; Marotz, Clarisse; Bryant, MacKenzie M.; Sanders, Karenina; Schwartz, Tara; Humphrey, Greg; Vasquez-Baeza, Yoshiki; Tripathi, Anupriya; Parida, Laxmi; Carrieri, Anna Paola; Beck, Kristen L.; Das, Promi; Gonzalez, Antonio; McDonald, Daniel; Ladau, Joshua; Karst, Soeren M.; Albertsen, Mads; Ackermann, Gail; DeReus, Jeff; Thomas, Torsten; Petras, Daniel; Shade, Ashley; Stegen, James; Song, Se Jin; Metz, Thomas O.; Swafford, Austin D.; Dorrestein, Pieter C.; Jansson, Janet K.; Gilbert, Jack A.; Knight, Rob; the Earth Microbiome Project 500 ConsortiumNature Microbiology (2022), 7 (12), 2128-2150CODEN: NMAICH; ISSN:2058-5276. (Nature Portfolio)Abstr.: Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics anal. of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liq. chromatog.-tandem mass spectrometry and gas chromatog. mass spectrometry). We used standardized protocols and anal. methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addn. to a ref. database for metagenomic and metabolomic data, we provide a framework for incorporating addnl. studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We addnl. show the power of certain chem., in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chem. ecol., and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment.
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530Zmora, N.; Zilberman-Schapira, G.; Suez, J.; Mor, U.; Dori-Bachash, M.; Bashiardes, S.; Kotler, E.; Zur, M.; Regev-Lehavi, D.; Brik, R. B.-Z. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell 2018, 174, 1388– 1405.e21, DOI: 10.1016/j.cell.2018.08.041530https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhs1Omu7bK&md5=908d0d3ebeb82249aea33d32ed64f363Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome FeaturesZmora, Niv; Zilberman-Schapira, Gili; Suez, Jotham; Mor, Uria; Dori-Bachash, Mally; Bashiardes, Stavros; Kotler, Eran; Zur, Maya; Regev-Lehavi, Dana; Brik, Rotem Ben-Zeev; Federici, Sara; Cohen, Yotam; Linevsky, Raquel; Rothschild, Daphna; Moor, Andreas E.; Ben-Moshe, Shani; Harmelin, Alon; Itzkovitz, Shalev; Maharshak, Nitsan; Shibolet, Oren; Shapiro, Hagit; Pevsner-Fischer, Meirav; Sharon, Itai; Halpern, Zamir; Segal, Eran; Elinav, EranCell (Cambridge, MA, United States) (2018), 174 (6), 1388-1405.e21CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-assocd. gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.
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531Zhu, G.; Zhao, J.; Zhang, H.; Chen, W.; Wang, G. Probiotics for mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis. Foods 2021, 10, 1672, DOI: 10.3390/foods10071672531https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXislCgu77M&md5=0ec20655d738b06303e4d76b36346b2bProbiotics for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-AnalysisZhu, Guangsu; Zhao, Jianxin; Zhang, Hao; Chen, Wei; Wang, GangFoods (2021), 10 (7), 1672CODEN: FOODBV; ISSN:2304-8158. (MDPI AG)Accumulating evidence from animal studies supports the potential role of probiotics and prebiotics in alleviating neurodegenerative diseases. However, whether dietary supplementation with probiotics improves cognitive function in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) is unclear. We searched literature databases for relevant randomized control trials and compared the outcomes between control/placebo and intervention groups. The results of the included studies were meta-analyzed using a random-effects model, with standardized mean differences (SMDs) and 95% confidence intervals (CIs) calcd. as summary statistics. We also performed a risk-of-bias assessment, sensitivity anal. and subgroup anal. Among the 294 articles identified, eight articles involving 174 patients with AD and 446 with MCI were included in the qual. synthesis and seven studies were meta-analyzed. Our anal. detected high between-group heterogeneity (SMD = 0.43, 95% CI -0.02-0.88, p < 0.0001, I2 = 86.4%) in cognitive function across the included studies. Subgroup analyses identified a significant effect of probiotics on cognitive function only in the studies involving people with MCI (I2 = 44%, p = 0.15 for heterogeneity, p = 0.0002 for overall effect). Our findings suggest that dietary supplementation with probiotics improves cognitive function, esp. in people with MCI.
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532Białecka-Dębek, A.; Granda, D.; Szmidt, M. K.; Zielińska, D. Gut microbiota, probiotic interventions, and cognitive function in the elderly: a review of current knowledge. Nutrients 2021, 13, 2514, DOI: 10.3390/nu13082514532https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVKgtrrL&md5=48c20a31877f490c3061c55c7c23fe11Gut Microbiota, Probiotic Interventions, and Cognitive Function in the Elderly: A Review of Current KnowledgeBialecka-Debek, Agata; Granda, Dominika; Szmidt, Maria Karolina; Zielinska, DorotaNutrients (2021), 13 (8), 2514CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)A review. Changes in the compn. and proportions of the gut microbiota may be assocd. with numerous diseases, including cognitive impairment. Over the recent years, the growing interest in this relation is obsd., but there are still many unknowns, esp. in the elderly. To the best of our knowledge, this is the first work that synthesizes and critically evaluates existing evidence on the possible assocn. between human gut microbiota and cognitive function in the elderly. For this purpose, comprehensive literature searches were conducted using the electronic databases PubMed, Google Scholar, and ScienceDirect. The gut microbiota of cognitively healthy and impaired elderly people may differ in the diversity and abundance of individual taxes, but specific taxes cannot be identified. However, some tendencies to changing the Firmicutes/Bacteroidetes ratio can be identified. Currently, clin. trials involving probiotics, prebiotics, and synbiotics supplementation have shown that there are premises for the claim that these factors can improve cognitive functions, however there is no single intervention beneficial to the elderly population. More reliable evidence from large-scale, long-period RCT is needed. Despite proposing several potential mechanisms of the gut microbiota's influence on the cognitive function impairment, prospective research on this topic is extremely difficult to conduct due to numerous confounding factors that may affect the gut microbiota. Heterogeneity of research outcomes impairs insight into these relations.
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533Munawar, N.; Ahsan, K.; Muhammad, K.; Ahmad, A.; Anwar, M. A.; Shah, I.; Al Ameri, A. K.; Al Mughairbi, F. Hidden role of gut microbiome dysbiosis in schizophrenia: Antipsychotics or psychobiotics as therapeutics?. Int. J. Mol. Sci. 2021, 22, 7671, DOI: 10.3390/ijms22147671533https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisVWiurnI&md5=7826b70c91ab23b267058b2d5e8d2acbHidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics?Munawar, Nayla; Ahsan, Khansa; Muhammad, Khalid; Ahmad, Aftab; Anwar, Munir A.; Shah, Iltaf; Al Ameri, Ahlam Khalifa; Al Mughairbi, FadwaInternational Journal of Molecular Sciences (2021), 22 (14), 7671CODEN: IJMCFK; ISSN:1422-0067. (MDPI AG)A review. Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiol. Mounting evidence indicates the involvement of genetics and epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, and environmental influence in the disease, but a single root cause and mechanism involved has yet to be conclusively detd. Consequently, the identification of diagnostic markers and the development of psychotic drugs for the treatment of schizophrenia faces a high failure rate. This article surveys the etiol. of schizophrenia with a particular focus on gut microbiota regulation and the microbial signaling system that correlates with the brain through the vagus nerve, enteric nervous system, immune system, and prodn. of postbiotics. Gut microbially produced mols. may lay the groundwork for further investigations into the role of gut microbiota dysbiosis and the pathophysiol. of schizophrenia. Current treatment of schizophrenia is limited to psychotherapy and antipsychotic drugs that have significant side effects. Therefore, alternative therapeutic options merit exploration. The use of psychobiotics alone or in combination with antipsychotics may promote the development of novel therapeutic strategies. In view of the individual gut microbiome structure and personalized response to antipsychotic drugs, a tailored and targeted manipulation of gut microbial diversity naturally by novel prebiotics (non-digestible fiber) may be a successful alternative therapeutic for the treatment of schizophrenia patients.
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534Cohen Kadosh, K.; Basso, M.; Knytl, P.; Johnstone, N.; Lau, J. Y. F.; Gibson, G. R. Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultation. Transl Psychiatry 2021, 11, 352, DOI: 10.1038/s41398-021-01422-7534https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB2c7osFKjtA%253D%253D&md5=7cb3ed10800b0f4e82de45e83fc925a4Psychobiotic interventions for anxiety in young people: a systematic review and meta-analysis, with youth consultationCohen Kadosh Kathrin; Basso Melissa; Knytl Paul; Johnstone Nicola; Lau Jennifer Y F; Gibson Glenn RTranslational psychiatry (2021), 11 (1), 352 ISSN:.The human gut microbiome influence on brain function and mental health is an emerging area of intensive research. Animal and human research indicates adolescence as a sensitive period when the gut-brain axis is fine-tuned, where dietary interventions to change the microbiome may have long-lasting consequences for mental health. This study reports a systematic review and meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, with discussion of a consultation on the acceptability of psychobiotic interventions for mental health management amongst youth with lived experience. Six databases were searched for controlled trials in human samples (age range: 10-24 years) seeking to reduce anxiety. Post intervention outcomes were extracted as standard mean differences (SMDs) and pooled based on a random-effects model. 5416 studies were identified: 14 eligible for systematic review and 10 eligible for meta-analysis (total of 324 experimental and 293 control subjects). The meta-analysis found heterogeneity I(2) was 12% and the pooled SMD was -0.03 (95% CI: -0.21, 0.14), indicating an absence of effect. One study presented with low bias risk, 5 with high, and 4 with uncertain risk. Accounting for risk, sensitivities analysis revealed a SMD of -0.16 (95% CI: -0.38, 0.07), indicative of minimal efficacy of psychobiotics for anxiety treatment in humans. There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding, and addressing the wider context, and would be welcomed by anxious youths.
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535Osadchiy, V.; Martin, C. R.; Mayer, E. A. The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications. Clin. Gastroenterol. Hepatol. 2019, 17, 322– 332, DOI: 10.1016/j.cgh.2018.10.002535https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1ymsrbE&md5=d1132fc4ba579bf4cd053d30824a3ee6The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical ImplicationsOsadchiy, Vadim; Martin, Clair R.; Mayer, Emeran A.Clinical Gastroenterology and Hepatology (2019), 17 (2), 322-332CODEN: CGHLAW; ISSN:1542-3565. (Elsevier)A review. Based largely on results from preclin. studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.We reviewed the preclin. and clin. literature related to the topic of brain gut microbiome interactions.Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.
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536Cussotto, S.; Strain, C. R.; Fouhy, F.; Strain, R. G.; Peterson, V. L.; Clarke, G.; Stanton, C.; Dinan, T. G.; Cryan, J. F. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology (Berl.) 2019, 236, 1671– 1685, DOI: 10.1007/s00213-018-5006-5536https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3ivVOqtQ%253D%253D&md5=f6d5677771d94453b101efb585dd9f9eDifferential effects of psychotropic drugs on microbiome composition and gastrointestinal functionCussotto Sofia; Strain Conall R; Fouhy Fiona; Strain Ronan G; Peterson Veronica L; Clarke Gerard; Stanton Catherine; Dinan Timothy G; Cryan John F; Cussotto Sofia; Peterson Veronica L; Cryan John F; Strain Conall R; Fouhy Fiona; Strain Ronan G; Stanton Catherine; Clarke Gerard; Stanton Catherine; Dinan Timothy GPsychopharmacology (2019), 236 (5), 1671-1685 ISSN:.RATIONALE: Growing evidence supports a role for the microbiota in regulating gut-brain interactions and, thus, psychiatric disorders. Despite substantial scientific efforts to delineate the mechanism of action of psychotropic medications at a central nervous system (CNS) level, there remains a critical lack of understanding on how these drugs might affect the microbiota and gut physiology. OBJECTIVES: We investigated the antimicrobial activity of psychotropics against two bacterial strain residents in the human gut, Lactobacillus rhamnosus and Escherichia coli. In addition, we examined the impact of chronic treatment with these drugs on microbiota and intestinal parameters in the rat. RESULTS: In vitro fluoxetine and escitalopram showed differential antimicrobial effects. Lithium, valproate and aripiprazole administration significantly increased microbial species richness and diversity, while the other treatments were not significantly different from controls. At the genus level, several species belonging to Clostridium, Peptoclostridium, Intestinibacter and Christenellaceae were increased following treatment with lithium, valproate and aripiprazole when compared to the control group. Animals treated with escitalopram, venlafaxine, fluoxetine and aripiprazole exhibited an increased permeability in the ileum. CONCLUSIONS: These data show that psychotropic medications differentially influence the composition of gut microbiota in vivo and that fluoxetine and escitalopram have specific antimicrobial activity in vitro. Interestingly, drugs that significantly altered gut microbial composition did not increase intestinal permeability, suggesting that the two factors are not causally linked. Overall, unravelling the impact of psychotropics on gastrointestinal and microbiota measures offers the potential to provide critical insight into the mechanism of action and side effects of these medications.
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Prebiotic, probiotic, postbiotic, and fecal transplant therapeutic clinical trial data investigating the treatment of mental disorders and DGBI through gut microbiome modulation (XLSX)
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