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Lactic acid bacteria and endogenous ethanol mediate proton pump inhibitor-associated MASLD: a multicohort

Mark Davids1, Hilde Herrema1, Albert K Groen1

  • 1Department of Experimental Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Gut Microbes
|May 3, 2026
PubMed
Abstract

Insights

Proton pump inhibitor (PPI) use may contribute to metabolic dysfunction associated with steatotic liver disease (MASLD) by altering the gut microbiome. Specifically, increased lactic acid bacteria abundance, potentially leading to higher ethanol levels, mediates this association.

Area of Science:

  • Gastroenterology
  • Microbiome Research
  • Metabolic Disease

Background:

  • Proton pump inhibitor (PPI) use is linked to metabolic dysfunction associated with steatotic liver disease (MASLD).
  • The gut microbiome is a potential mediator in this association, independent of traditional risk factors like BMI and age.

Purpose of the Study:

  • To identify bacterial clades with the highest mediating potential in the PPI-MASLD association.
  • To evaluate the serial mediation pathway involving microbially derived endogenous ethanol.

Main Methods:

  • Microbiome mediation analysis was performed in bariatric surgery, HELIUS, and FINRISK cohorts.
  • Outcomes included liver biopsy-proven steatosis grade, postprandial ethanol concentrations, and Fatty Liver Index (FLI) score.

Main Results:

  • The Lactobacillales order demonstrated the strongest mediating potential across tested outcomes.
  • A serial mediation pathway was identified: PPI use -> Lactobacillales abundance -> postprandial ethanol -> MASLD/FLI.

Conclusions:

  • The microbiome mediates the association between PPI use and hepatic steatosis.
  • Increased lactic acid bacteria (Lactobacillales) abundance is a key mediator, potentially involving endogenous ethanol production.
Keywords:
MASLDethanolfermentationgastrointestinal microbiomelactobacillalesmediation analysisobesityproton pump inhibitorssmall intestine

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