PRESENTATIONSRole of Gut Microbiota in Liver DiseaseBrenner, David A. MD*; Paik, Yong-Han MD, PhD†,‡; Schnabl, Bernd MD* Author Information *Department of Medicine, University of California San Diego, La Jolla, CA †Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine ‡Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Korea Supported by National Institutes of Health (R01 GM041804-26, P50 AA011999-16, P42 ES010337-13, U01 AA021856-02, R01 DK101737-01A1, U01 AA022614-01A1, R01 DK099205-01A1; B.S.: R01 AA020703, U01 AA02185). The authors declare that they have nothing to disclose. Reprints: David A. Brenner, MD, Department of Medicine, University of California San Diego, 9500 Gilman Drive #0602, La Jolla, CA 92093 (e-mail: [email protected]). Journal of Clinical Gastroenterology: November/December 2015 - Volume 49 - Issue - p S25-S27 doi: 10.1097/MCG.0000000000000391 Buy Metrics Abstract Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.