Gut Microbiota-Derived Mediators as Potential Markers in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common, multifactorial, and poorly understood liver disease whose incidence is globally rising. During the past decade, several lines of evidence suggest that dysbiosis of intestinal microbiome represents an important factor contributing to NAFLD occurrence and its progression into NASH. The mechanisms that associate dysbiosis with NAFLD include changes in microbiota-derived mediators, deregulation of the gut endothelial barrier, translocation of mediators of dysbiosis, and hepatic inflammation. Changes in short chain fatty acids, bile acids, bacterial components, choline, and ethanol are the result of altered intestinal microbiota. We perform a narrative review of the previously published evidence and discuss the use of gut microbiota-derived mediators as potential markers in NAFLD.

Figure 1

A schematic figure of the role of gut dysbiosis in the development and progression of nonalcoholic fatty liver disease (NAFLD) on the basis of the gut-liver axis. Environmental factors as obesity, high fat diet, or infection (among others) may induce intestinal dysbiosis and also increased intestinal permeability (malfunction of tight junctions). Substances such as short-chain fatty acids, bile acids, bacterial components, choline, and endogenous ethanol reach the liver and activation of toll-like receptors (TLRs) occurs. This activation induces insulin resistance, hepatic inflammation, lipogenesis, and oxidative stress, inducing NAFLD. BA, bile acids; LPS, lipopolysaccharides; SCFA, short chain fatty acid; TLR, toll-like receptor; TMAO, trimethylamine oxide.