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

Cristina Llorente, Peter Jepsen, Tatsuo Inamine, Lirui Wang, Sena Bluemel, Hui J. Wang, Rohit Loomba, Jasmohan S. Bajaj, Mitchell L. Schubert, Masoumeh Sikaroodi, Patrick M. Gillevet, Jun Xu, Tatiana Kisseleva, Samuel B. Ho, Jessica DePew, Xin Du, Henrik T. Sørensen, Hendrik Vilstrup, Karen E. Nelson, David A. Brenner, Derrick E. Fouts and Bernd Schnabl ()
Additional contact information
Cristina Llorente: University of California San Diego
Peter Jepsen: Aarhus University Hospital
Tatsuo Inamine: University of California San Diego
Lirui Wang: University of California San Diego
Sena Bluemel: University of California San Diego
Hui J. Wang: University of California San Diego
Rohit Loomba: University of California San Diego
Jasmohan S. Bajaj: Virginia Commonwealth University and McGuire VA Medical Center
Mitchell L. Schubert: Virginia Commonwealth University and McGuire VA Medical Center
Masoumeh Sikaroodi: George Mason University
Patrick M. Gillevet: George Mason University
Jun Xu: University of California San Diego
Tatiana Kisseleva: University of California San Diego
Samuel B. Ho: University of California San Diego
Jessica DePew: J. Craig Venter Institute
Xin Du: University of California San Diego
Henrik T. Sørensen: Aarhus University Hospital
Hendrik Vilstrup: Aarhus University Hospital
Karen E. Nelson: J. Craig Venter Institute
David A. Brenner: University of California San Diego
Derrick E. Fouts: J. Craig Venter Institute
Bernd Schnabl: University of California San Diego

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00796-x

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