Microbiome in specific diseases
Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

https://doi.org/10.1016/j.cgh.2018.08.065 Get rights and content

The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. ‘Dysbiosis’ of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and exogenous factors, such as nutritional intake and xenobiotic exposure, can alter the gut microbiome. We will review the evolving methods for studying the gut microbiome and how these profiling techniques have been utilized to further our understanding of the gut microbial community composition and functional potential in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions that may contribute to the pathogenesis of NAFLD, with a primary focus on mechanisms related to the metabolic output of the gut microbiome. Finally, we will discuss potential therapeutic implications of the gut microbiome in NAFLD.

Section snippets

Methods for Gut Microbiome Profiling

Advances in profiling and analytic techniques are transforming microbiome research and have been recently reviewed elsewhere,5, 6 so we limit our discussion to an overview of methods that have been used in human studies in NAFLD (Figure 1). To date, most studies have used culture-independent, biomarker-based profiling techniques. This method involves sequencing a ubiquitous gene, which is represented by the 16S ribosomal RNA (16S rRNA) gene in bacteria. Biomarker-based profiling techniques

Human Gut Microbiome Profiles in Clinical Phenotypes of Nonalcoholic Fatty Liver Disease: Community Composition

Numerous human studies have demonstrated an association between gut dysbiosis and the spectrum of NAFLD in children7, 8, 9, 10 and adults.11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 All except 1 of these studies were cross-sectional,12 and most used biomarker-based sequencing to profile the gut microbiome. We review gut microbiome profiles, with a focus on genus-level differences, in the following clinical phenotypes: nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH),

Human Gut Microbiome Profiles in Clinical Phenotypes of Nonalcoholic Fatty Liver Disease: Functional Potential

Several human studies have used “omics” techniques and thus added new perspectives on functional attributes of the gut microbiome in NAFL-, NASH-, and NAFLD-related advanced fibrosis.7, 8, 9, 11, 13, 17, 18, 21, 22 Results from fecal and serum metabolite profiling are listed in Table 1. To date, no human studies have functionally profiled the gut microbiome in NAFLD-related HCC.

Postulated Mechanisms Linking the Gut Microbiome to Nonalcoholic Fatty Liver Disease

Although human studies have yielded insight into functional attributes of the gut microbiota in NAFLD, much of the mechanistic evidence linking the gut microbiome and NAFLD pathogenesis has been obtained from experiments in animal models. We summarize the current evidence for postulated microbiome-associated mechanisms contributing to the pathogenesis of NAFLD (Figure 2).

The Gut Microbiome and Nonalcoholic Fatty Liver Disease: From Research to Bedside

Microbiome-targeted therapy (MTT) is considered to include antibiotics, probiotics (culture of living microorganisms that could have health benefits for the human host), prebiotics (fermentable dietary fibers that stimulate the growth and survival of probiotics), synbiotics (combination of probiotics and prebiotics), and FMT.1 High-quality, large-scale clinical interventional trials examining MTT in NAFLD are lacking. Several randomized controlled trials have examined the use of non-FMT MTT in

Conclusions

In summary, preclinical evidence supports a causal role of gut microbiome in liver disease progression in NAFLD. However, there is much that is not understood about the gut-liver axis. Because of the cross-sectional nature of published human data, along with methods used for microbial profiling, most clinical evidence supports an association between dysbiosis and NAFLD, but mechanistic links have not been well established. Further well-designed, longitudinal, prospective cohort studies with

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    Conflicts of interest The authors disclose no conflicts.

    Funding The authors disclose the following: Suzanne Sharpton is supported by the National Research Service Award (2T32DK060414-16) from the National Institute of Diabetes and Digestive and Kidney Diseases. Veeral Ajmera is supported by the Advanced/Transplant Hepatology Fellowship and the Alan Hofmann Clinical and Translational Research Award from the AASLD Foundation. Rohit Loomba is supported by National Institutes of Health (R01-DK106419-02).

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