The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD)

Abstract

NAFLD is currently the main cause of chronic liver disease in developed countries, and the number of NAFLD patients is growing worldwide. NAFLD often has similar symptoms to other metabolic disorders, including type 2 diabetes and obesity. Recently, the role of the gut microbiota in the pathophysiology of many diseases has been revealed. Regarding NAFLD, experiments using gut microbiota transplants to germ-free animal models showed that fatty liver disease development is determined by gut bacteria. Moreover, the perturbation of the composition of the gut microbiota has been observed in patients suffering from NAFLD. Numerous mechanisms relating the gut microbiome to NAFLD have been proposed, including the dysbiosis-induced dysregulation of gut endothelial barrier function that allows for the translocation of bacterial components and leads to hepatic inflammation. In addition, the various metabolites produced by the gut microbiota may impact the liver and thus modulate NAFLD susceptibility. Therefore, the manipulation of the gut microbiome by probiotics, prebiotics or synbiotics was shown to improve liver phenotype in NAFLD patients as well as in rodent models. Hence, further knowledge about the interactions among dysbiosis, environmental factors, and diet and their impacts on the gut-liver axis can improve the treatment of this life-threatening liver disease and its related disorders.

Keywords: Antibiotics; Bile acids; Dysbiosis; Germ-free animals; Gut microbiota; Intestinal permeability; Metabolic syndrome; Non-alcoholic fatty liver disease; Prebiotics; Probiotics.

Fig. 1

The mechanisms linking the microbiome to NAFLD development. Perturbation in the intestinal microbiota composition or function can result in increased gut permeability and facilitation of the passage of LPS and other inflammatory factors to the blood, decreased choline availability, changes in bile acid composition and increased ethanol production in the intestine. These factors and metabolites together with dietary lipids can result in liver steatosis, inflammation and, eventually, NASH development

Fig. 2

Schematic view of the role of the microbiome in gut permeability and NAFLD development. On the left side, the gut–liver axis components are operating normally; on the right side, NAFLD status is shown. The dysbiotic microbiome, together with the changed intestinal barrier due to the malfunction of the tight junctions, facilitates the translocation of some bacterial products into the portal vein. These bacterial products interact with Toll-like receptors (TLRs) on the surface of the hepatic cells, which leads to inflammation and NAFLD development