Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus

作者：Cristina Llorente, Peter Jepsen, Tatsuo Inamine, Lirui Wang, Sena Bluemel, Hui J. Wang, Rohit Seth Loomba, Jasmohan Singh Bajaj, Mitchell L. Schubert, Masoumeh Sikaroodi, Patrick Martin Gillevet, Jun Xu, Tatiana Kisseleva, Samuel B. Ho, Jessica DePew, Xin Du, Henrik Toft Sørensen, Hendrik Vilstrup, Karen E. Nelson, David A. Brenner, Derrick E. Fouts, Bernd Schnabl · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/s41467-017-00796-x · 被引用次数：258 · 研究领域：Liver Disease Diagnosis and Treatment、Alcohol Consumption and Health Effects、Diet, Metabolism, and Disease

Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease.Proton pump inhibitors (PPIs) reduce gastric acid secretion and modulate gut microbiota composition. Here Llorente et al. show that PPIs induce bacterial overgrowth of enterococci, which, in turn, exacerbate ethanol-induced liver disease both in mice and humans.