Non-alcoholic fatty liver and the gut microbiota

Abstract

Background: Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and poorly understood liver disease whose incidence is globally rising. NAFLD is generally asymptomatic and associated with other manifestations of the metabolic syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. In recent years, several lines of evidence suggest that the gut microbiome represents a significant environmental factor contributing to NAFLD development and its progression into NASH. Suggested microbiome-associated mechanisms contributing to NAFLD and NASH include dysbiosis-induced deregulation of the gut endothelial barrier function, which facilitates systemic bacterial translocation, and intestinal and hepatic inflammation. Furthermore, increased microbiome-modulated metabolites such as lipopolysaccharides, short chain fatty acids (SCFAs), bile acids, and ethanol, may affect liver pathology through multiple direct and indirect mechanisms.

Scope of review: Herein, we discuss the associations, mechanisms, and clinical implications of the microbiome's contribution to NAFLD and NASH. Understanding these contributions to the development of fatty liver pathogenesis and its clinical course may serve as a basis for development of therapeutic microbiome-targeting approaches for treatment and prevention of NAFLD and NASH.

Major conclusions: Intestinal host-microbiome interactions play diverse roles in the pathogenesis and progression of NAFLD and NASH. Elucidation of the mechanisms driving these microbial effects on the pathogenesis of NAFLD and NASH may enable to identify new diagnostic and therapeutic targets of these common metabolic liver diseases. This article is part of a special issue on microbiota.

Keywords: Liver; Microbiome; NAFLD; NASH.

Figure 1

Suggested mechanisms for the effect of gut microbiome in NAFLD development and progression to NASH. Bacterial metabolites such as SCFA and bile acids may be potently involved in normal liver function and reduced liver lipogenesis and inflammation. Aberrations in commensal microbiome composition, diversity, and function may lead to increased gut permeability, production of LPS and other inflammatory factor, recued diversity of bile acids, and production of ethanol. All these metabolites and factors in combination with lipids derived from the diet can cause liver steatosis, inflammation and damage, which may lead to hepatic fibrosis, scarring, and NASH development.