Role of gut microbiota in liver diseases

The liver constantly encounters food-derived antigens and bacterial components such as lipopolysaccharide translocated from the gut into the portal vein. Bacterial components stimulate Toll-like receptors (TLR), which are expressed on Kupffer cells, biliary epithelial cells, hepatocytes, hepatic stellate cells, endothelial cells and dendritic cells and recognize specific pathogen-associated molecular patterns. The signaling of TLR to its main ligand triggers inflammation. Usually, in order to protect against hyperactivation of the immune system and to prevent organ failure by persistent inflammation, TLR tolerance to repeated stimuli is induced. In chronic liver diseases, a breakdown in TLR tolerance occurs. Furthermore, Kupffer cells, hepatic stellate cells and natural killer T cells are key components of innate immunity. Decreased numbers and impaired ability of these cells lead to failures in immune tolerance, resulting in persistent inflammation. Recently, the activation of inflammasome was revealed to control the secretion of pro-inflammatory cytokines such as interleukin-1β in response to bacterial pathogens. Innate immunity seems to be an important contributor to the pathogenesis of fatty liver disease and autoimmune liver disease. Recently, probiotics were reported to affect various liver diseases via shifts in gut microbiota and the stability of intestinal permeability. However, many unresolved questions remain. Further analysis will be needed to gain a more comprehensive understanding of the association of innate immunity with the pathogenesis of various liver diseases.