Approximately a trillion microbial cells colonize the mammalian intestine; these are collectively termed gut microbiota. Gut microbiota play a critical role in many physiological and pathological processes, influencing host immunity and metabolism. Gut dysbiosis is related to not only intestinal but also extra-intestinal diseases, including nervous system, respiratory, cardiovascular system, and liver diseases.
The liver is the largest internal organ and gland in the human body, which receives blood both from the portal vein and hepatic artery. Therefore, the liver is exposed to gut microbes as well as their metabolites and products. Previous studies showed that live commensal bacteria can be sampled by intestinal dendritic cells (DC) and transferred to the liver through the lymphatic route or portal vein. In healthy mice, the liver can act as a second firewall in which Kupffer cells can capture and clean commensal bacteria from the systemic vasculature. The healthy liver can maintain sterility by removing not only live commensal bacteria but also microbial metabolites and products.
Gut microbiota dysbiosis is related to chronic liver diseases, including alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune liver disease, chronic hepatitis B and C, liver cirrhosis, and hepatocellular carcinoma (HCC). In mice, gut microbiota depletion was found to impair the HBV-specific T cell response and prolong HBV infection. In patients with hepatitis B-related cirrhosis, the gut microbiota community and metabolism mediated by the gut microbiota was significantly changed when compared with healthy controls. Reconstitution of the gut microbiota using fecal microbiota transplantation (FMT) facilitated hepatitis B virus e-antigen (HBeAg) clearance in patients with HBeAg-positive chronic hepatitis B after long-term antiviral therapy. FMT is also a potent therapy strategy for hepatic encephalopathy.