Abstract
Considering the increasing prevalence of obesity worldwide, new approaches for its control have been investigated. Recent evidences highlighted the role of the gut microbiome in weight management. Obesity-associated gut microbiota alters host energy uptake, insulin sensitivity, inflammation, and fat storage. Moreover, the gut microbiota-derived metabolites could control appetite directly by affecting the central nervous system or indirectly through modifying the gut hormones secretion. Metabolites of the gut microbiome-brain axis could be novel targets for designing drugs in obesity. They can be prescribed directly like butyrate or can be modulated by manipulating the gut microbiota through probiotics, prebiotics and other dietary components such as polyphenols. Microbiome studies are trying to identify novel microbial species as next-generation probiotics to restore healthy gut microbiota composition and combat obesity and its related complications. According to the relationships between the gut microbiota and microbial composition of other parts of the body, the mechanisms linking the gut-brain axis and the whole human microbiota should be elucidated to provide novel anti-obesity strategies.
Similar content being viewed by others
Data availability
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
References
Ejtahed HS, Angoorani P, Hasani-Ranjbar S, Siadat SD, Ghasemi N, Larijani B, et al. Adaptation of human gut microbiota to bariatric surgeries in morbidly obese patients: a systematic review. Microb Pathog. 2018;116:13–21.
Ejtahed HS, Soroush AR, Angoorani P, Larijani B, Hasani-Ranjbar S. Gut microbiota as a target in the pathogenesis of metabolic disorders: a new approach to novel therapeutic agents. Horm Metab Res. 2016;48(6):349–58.
Torres-Fuentes C, Schellekens H, Dinan TG, Cryan JF. The microbiota-gut-brain axis in obesity. Lancet Gastroenterol Hepatol. 2017;2(10):747–56.
Moran-Ramos S, Lopez-Contreras BE, Canizales-Quinteros S. Gut microbiota in obesity and metabolic abnormalities: a matter of composition or functionality? Arch Med Res. 2017;48(8):735–53.
Ejtahed HS, Hasani-Ranjbar S, Larijani B. Human microbiome as an approach to personalized medicine. Altern Ther Health Med. 2017;23(6):8–9.
Krajmalnik-Brown R, Ilhan ZE, Kang DW, DiBaise JK. Effects of gut microbes on nutrient absorption and energy regulation. Nutr Clin Pract. 2012;27(2):201–14.
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–72.
Vaure C, Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol. 2014;5:316.
Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701–12.
Everard A, Cani PD. Gut microbiota and GLP-1. Rev Endocr Metab Disord. 2014;15(3):189–96.
Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR, et al. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 2005;1044(1):127–31.
Berthoud HR. The vagus nerve, food intake and obesity. Regul Pept. 2008;149(1–3):15–25.
Wang L, Li P, Tang Z, Yan X, Feng B. Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of Liraglutide and Saxagliptin treatment. Sci Rep. 2016;6:33251.
Pichette J, Fynn-Sackey N, Gagnon J. Hydrogen sulfide and sulfate prebiotic stimulates the secretion of Glp-1 and improves Glycemia in male mice. Endocrinology. 2017;158(10):3416–25.
van de Wouw M, Boehme M, Lyte JM, Wiley N, Strain C, O'Sullivan O, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol. 2018.
Liu H, Wang J, He T, Becker S, Zhang G, Li D, et al. Butyrate: a double-edged sword for health? Adv Nutr. 2018;9(1):21–9.
Aguilar EC, da Silva JF, Navia-Pelaez JM, Leonel AJ, Lopes LG, Menezes-Garcia Z, et al. Sodium butyrate modulates adipocyte expansion, adipogenesis, and insulin receptor signaling by upregulation of PPAR-gamma in obese Apo E knockout mice. Nutrition. 2018;47:75–82.
Li Z, Yi CX, Katiraei S, Kooijman S, Zhou E, Chung CK, et al. Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit. Gut. 2018;67(7):1269–79.
de Vadder F, Mithieux G. Gut-brain signaling in energy homeostasis: the unexpected role of microbiota-derived succinate. J Endocrinol. 2018;236(2):R105–R8.
De Vadder F, Kovatcheva-Datchary P, Zitoun C, Duchampt A, Backhed F, Mithieux G. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis. Cell Metab. 2016;24(1):151–7.
Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Ther Adv Gastroenterol. 2013;6(1):39–51.
Bindels LB, Delzenne NM, Cani PD, Walter J. Towards a more comprehensive concept for prebiotics. Nat Rev Gastroenterol Hepatol. 2015;12(5):303–10.
O'Toole PW, Marchesi JR, Hill C. Next-generation probiotics: the Spectrum from probiotics to live biotherapeutics. Nat Microbiol. 2017;2:17057.
Author information
Authors and Affiliations
Contributions
HE drafted the manuscript. SH designed the study and helped to draft the manuscript. Both authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Not applicable.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ejtahed, HS., Hasani-Ranjbar, S. Neuromodulatory effect of microbiome on gut-brain axis; new target for obesity drugs. J Diabetes Metab Disord 18, 263–265 (2019). https://doi.org/10.1007/s40200-019-00384-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40200-019-00384-4