Llorente Cristina, Jepsen Peter, Inamine Tatsuo, Wang Lirui, Bluemel Sena, Wang Hui J, Loomba Rohit, Bajaj Jasmohan S, Schubert Mitchell L, Sikaroodi Masoumeh, Gillevet Patrick M, Xu Jun, Kisseleva Tatiana, Ho Samuel B, DePew Jessica, Du Xin, Sørensen Henrik T, Vilstrup Hendrik, Nelson Karen E, Brenner David A, Fouts Derrick E, Schnabl Bernd
Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Department of Medicine, VA San Diego Healthcare System, San Diego, CA, 92161, USA.
Nat Commun. 2017 Oct 16;8(1):837. doi: 10.1038/s41467-017-00796-x.
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.
在西方国家，慢性肝病的发病率正在上升，肝硬化是全球第12大死因。与此同时，胃酸抑制药物的使用也在增加。在此，我们表明质子泵抑制剂通过增加肠道肠球菌属的数量，促进小鼠酒精性肝病、非酒精性脂肪性肝病和非酒精性脂肪性肝炎的进展。移位的肠球菌会导致肝脏炎症和肝细胞死亡。肠道粪肠球菌的扩增足以加剧小鼠的乙醇诱导性肝病。使用质子泵抑制剂会增加酒精依赖患者患酒精性肝病的风险。因此，基于小鼠模型和人类的数据，胃酸分泌减少似乎会促进肠道肠球菌过度生长，进而促进肝病。近期胃酸抑制药物使用的增加可能导致了慢性肝病发病率的上升。质子泵抑制剂（PPIs）可减少胃酸分泌并调节肠道微生物群组成。在此，洛伦特等人表明，质子泵抑制剂会诱导肠球菌的细菌过度生长，进而在小鼠和人类中加剧乙醇诱导性肝病。
