Evidence map›Paper›PMID 29038503›Full record

ArticleNature communications2017

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 and 12 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 131 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 3 pooled it
18.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 246 citations in OpenAlex.

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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 3 countries.

Cristina LlorenteDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0001-8135-9186
Peter JepsenDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, 8000, Denmark.
Tatsuo InamineDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Lirui WangDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Sena BluemelDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Hui J WangDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0003-2654-0243
Rohit LoombaDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Jasmohan S BajajDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, USA.
Mitchell L SchubertDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, 23249, USA.
Masoumeh SikaroodiMicrobiome Analysis Center, George Mason University, Manassas, VA, 20110, USA.
Patrick M GillevetMicrobiome Analysis Center, George Mason University, Manassas, VA, 20110, USA.
Jun XuDepartment of Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
Tatiana KisselevaDepartment of Surgery, University of California San Diego, La Jolla, CA, 92093, USA.
Samuel B HoDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Jessica DePewJ. Craig Venter Institute, Rockville, MD, 20850, USA.
Xin DuDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Henrik T SørensenDepartment of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 8000, Denmark.
Hendrik VilstrupDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, 8000, Denmark.
Karen E NelsonJ. Craig Venter Institute, Rockville, MD, 20850, USA.
David A BrennerDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Derrick E FoutsJ. Craig Venter Institute, Rockville, MD, 20850, USA.
Bernd SchnablDepartment of Medicine, University of California San Diego, La Jolla, CA, 92093, USA. beschnabl@ucsd.edu.
University of California San Diego · USAarhus University Hospital · DKJ. Craig Venter Institute · USGeorge Mason University · USVirginia Commonwealth University · US

Funding

Microbiome and intestinal innate immune response in alcoholic liver diseaseR01AA020703 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHNABL, BERND G. · 2011 to 2020
$3.6M
Microbiome as Therapeutic Target in Alcoholic HepatitisU01AA021856 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., SCHNABL, BERND G. · 2013 to 2017
$2.1M
The Role of the Intestinal Mycobiome in Alcoholic Liver DiseaseU01AA024726 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SCHNABL, BERND G. · 2017 to 2017
$353k
The Commensal Microflora Suppresses Liver FibrosisI01BX002213 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI SCHNABL, BERND G. · 2015 to 2018
–
BLRD VA I01 BX002213NIAAA NIH HHS R01 AA020703NIAAA NIH HHS U01 AA021856NIAAA NIH HHS U01 AA024726
6 · The paper itself

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.

Indexed as

AnimalsDisease ProgressionEnterococcusFemaleGastric AcidHumansIncidenceLiver Diseases, AlcoholicMaleMiceMice, Inbred C57BLMicrobiotaNon-alcoholic Fatty Liver DiseaseProton Pump InhibitorsProton Pump Inhibitors

Identifiers

PMID29038503
PMCPMC5643518
OpenAlexW2761437180

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.