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

Author

Listed:
  • Cristina Llorente

    (University of California San Diego
    VA San Diego Healthcare System)

  • Peter Jepsen

    (Aarhus University Hospital
    Aarhus University Hospital)

  • Tatsuo Inamine

    (University of California San Diego
    Nagasaki University Graduate School of Biomedical Sciences)

  • Lirui Wang

    (University of California San Diego
    VA San Diego Healthcare System)

  • 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
    VA San Diego Healthcare System)

  • 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
    VA San Diego Healthcare System)

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.

Suggested Citation

  • 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 X, 2017. "Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00796-x
    DOI: 10.1038/s41467-017-00796-x
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    Cited by:

    1. Yi Duan & Huikuan Chu & Katharina Brandl & Lu Jiang & Suling Zeng & Nairika Meshgin & Eleni Papachristoforou & Josepmaria Argemi & Beatriz G. Mendes & Yanhan Wang & Hua Su & Weizhong Sun & Cristina Ll, 2021. "CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Bin Xia & Qiangsheng He & Fang Gao Smith & V. Georgios Gkoutos & Krishnarajah Nirantharakumar & Zi Chong Kuo & Danni Wang & Qi Feng & Eddie C. Cheung & Lunzhi Dai & Junjie Huang & Yuanyuan Yu & Wenbo , 2024. "Individualized prevention of proton pump inhibitor related adverse events by risk stratification," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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