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Nat Commun. 2017 Oct 16;8(1):837. doi: 10.1038/s41467-017-00796-x.

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

Author information

1
Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
2
Department of Medicine, VA San Diego Healthcare System, San Diego, CA, 92161, USA.
3
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, 8000, Denmark.
4
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 8000, Denmark.
5
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
6
Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, USA.
7
Microbiome Analysis Center, George Mason University, Manassas, VA, 20110, USA.
8
Department of Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
9
J. Craig Venter Institute, Rockville, MD, 20850, USA.
10
Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. beschnabl@ucsd.edu.
11
Department of Medicine, VA San Diego Healthcare System, San Diego, CA, 92161, USA. beschnabl@ucsd.edu.

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.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.

PMID:
29038503
PMCID:
PMC5643518
DOI:
10.1038/s41467-017-00796-x
[Indexed for MEDLINE]
Free PMC Article

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