The intestinal microbiota and microenvironment in liver.

The intestinal microbiome plays a significant role in the development of autoimmune diseases, in particular, inflammatory bowel diseases. But the interplay between the intestinal tract and the liver may explain the increased association with autoimmune liver diseases and inflammatory bowel diseases. The gut-liver axis involves multiple inflammatory cell types and cytokines, chemokines and other molecules which lead to the destruction of normal liver architecture. Triggers for the initiation of these events are unclear, but appear to include multiple environmental factors, including pathogenic or even commensal microbial agents. The variation in the gut microbiome has been cited as a major factor in the pathogenesis of autoimmune liver disease and even other autoimmune diseases. The unique positioning of the liver at the juncture of the peripheral circulation and the portal circulation augments the interaction between naïve T cells and other hepatic cells and leads to the disruption in the development of tolerance to commensal bacteria and other environmental agents. Finally, the innate immune system and in particular toll-like receptors play a significant role in the pathogenesis of autoimmune liver disease.