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

Abstract

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.

Keywords: Microbiota; Nonalcoholic Fatty Liver.

Figure 1.

Methods for characterization of the gut microbiome.

Figure 2.. Postulated mechanisms linking the gut microbiome to nonalcoholic fatty liver disease.

Impairment of intestinal epithelial function, via disrupted tight junctions, leads to endotoxemia and induction of toll-like receptor 4 (TLR4). Dietary choline is metabolized by the gut microbiome to produce trimethylamine (TMA), which reduces choline bioavailability. Indigestable carbohydrates (e.g. dietary fiber) undergo fermentation by the gut microbiome and give rise to short-chain fatty acids (SCFAs). The gut microbiome metabolizes bile acids, thus regulating the bile acid pool and leading to alterations in farnesoid X receptor (FXR) signaling. Ethanol can be generated by the gut microbiome. The gut microbiome may contribute to disruptions in amino acid homeostasis (not pictured).