The Liver at the Nexus of Host-Microbial Interactions.

The liver receives blood from the intestine, from the spleen, and directly from the heart and holds a vital position in vertebrate physiology. It plays a role in intermediary metabolism, bile secretion, maintaining blood sterility, serum homeostasis, xenobiotic detoxification, and immunological activity. This article provides our perspective on the liver as a nexus in establishing and maintaining host microbial mutualism. We discuss the role of the liver not only in sanitizing the blood stream from penetrant live microbes, but also in metabolizing xenobiotics that are synthesized or modified by intestinal microbes, and how microbiota modify the signaling potential of bile acids. The combination of bile acids as hormones and the metabolic control from pervasive effects of other absorbed microbial molecules powerfully shape hepatic metabolism. In addition, intestinal microbial metabolites can be sensed by liver-resident immune cells, which may disturb liver homeostasis, leading to fibrosis and liver cancer.