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 meta-bolism.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 pro-vided 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.

Alcoholic liver disease is a leading cause of morbidity and liver-related death worldwide. Intestinal bacterial overgrowth and dysbiosis induced by ethanol ingestion play an important role in the pathogenesis of alcoholic liver disease. After exposure to alcohol in the lumen, enteric bacteria alter their metabolism and thereby disturb intestinal homeostasis. Disruption of the mucosal barrier results in the translocation of microbial products that contribute to liver disease by inducing hepatic inflammation. In this review, we will discuss the effects of alcohol on the intestinal microbiome, and in particular, its effects on bacterial metabolism, bacterial translocation and ecological balance. A better understanding of the interactions among alcohol, the host and the microbiome will reveal new targets for therapy and lead to new treatments.
Bacterial Translocation/physiology ; Central Nervous System Depressants/metabolism ; Ethanol/metabolism ; Humans ; Intestines/*microbiology ; Lipopolysaccharides/physiology ; Liver Diseases, Alcoholic/*microbiology ; Microbiota/*physiology ; Permeability

Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3β and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.

No abstract available.
*Hospitalization ; Humans ; *Liver Cirrhosis