Current Research on the Pathogenesis of NAFLD/NASH and the Gut-Liver Axis: Gut Microbiota, Dysbiosis, and Leaky-Gut Syndrome

Abstract

Global lifestyle changes have led to an increased incidence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), requiring further in-depth research to understand the mechanisms and develop new therapeutic strategies. In particular, high-fat and high-fructose diets have been shown to increase intestinal permeability, which can expose the liver to endotoxins. Indeed, accumulating evidence points to a link between these liver diseases and the intestinal axis, including dysbiosis of the gut microbiome and leaky-gut syndrome. Here, we review the mechanisms contributing to these links between the liver and small intestine in the pathogenesis of NAFLD/NASH, focusing on the roles of intestinal microbiota and their metabolites to influence enzymes essential for proper liver metabolism and function. Advances in next-generation sequencing technology have facilitated analyses of the metagenome, providing new insights into the roles of the intestinal microbiota and their functions in physiological and pathological mechanisms. This review summarizes recent research linking the gut microbiome to liver diseases, offering new research directions to elucidate the detailed mechanisms and novel targets for treatment and prevention.

Keywords: dysbiosis; gut microbiota; gut–liver axis; leaky-gut syndrome; non-alcoholic fatty liver disease.

Figure 1

Schematic diagram of the gut–liver axis in non-alcoholic fatty liver disease/non-alcohol fatty liver disease. NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; SCFA, short chain fatty acids.