Gut microbiota,fatty liver disease,and hepatocellular carcinoma

Intestinal bacteria contribute to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Recently developed microbial profiling techniques are beginning to shed light on the nature of the changes in the gut microbiota that accompany NAFLD and non-alcoholic steatohepatitis(NASH).In this review,we summarize the role of gut microbiota in the development of NAFLD,NASH,and hepatocellular carcinoma(HCC).We highlight the mechanisms by which gut microbiota contribute to NAFLD/NASH,including through alterations in gut epithelial permeability,choline metabolism,endogenous alcohol production,release of inflammatory cytokines,regulation of hepatic Toll-like receptor(TLR),and bile acid metabolism.In addition,we analyze possible mechanisms for enhanced hepatic carcinogenesis,including alterations in bile acid metabolism,release of inflammatory cytokines,and expression of TLR-4.Finally,we describe therapeutic approaches for NAFLD/NASH and preventive strategies for HCC involving modulation of the intestinal microbiota or affected host pathways.Although recent studies have provided useful information,large-scale prospective studies are required to better characterize the intestinal microbiota and metabolome,in order to demonstrate a causative role for changes in the gut microbiota in the etiology of NAFLD/NASH,to identify new therapeutic strategies for NAFLD/NASH,and to develop more effective methods of preventing HCC.