Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial

Gastroenterology. 2015 Oct;149(4):883-5.e9. doi: 10.1053/j.gastro.2015.06.043. Epub 2015 Jul 9.


We conducted an open-label crossover trial to test whether proton pump inhibitors (PPIs) affect the gastrointestinal microbiome to facilitate Clostridium difficile infection (CDI). Twelve healthy volunteers each donated 2 baseline fecal samples, 4 weeks apart (at weeks 0 and 4). They then took PPIs for 4 weeks (40 mg omeprazole, twice daily) and fecal samples were collected at week 8. Six individuals took the PPIs for an additional 4 weeks (from week 8 to 12) and fecal samples were collected from all subjects at week 12. Samples were analyzed by 16S ribosomal RNA gene sequencing. We found no significant within-individual difference in microbiome diversity when we compared changes during baseline vs changes on PPIs. There were, however, significant changes during PPI use in taxa associated with CDI (increased Enterococcaceae and Streptococcaceae, decreased Clostridiales) and taxa associated with gastrointestinal bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae). In a functional analysis, there were no changes in bile acids on PPIs, but there was an increase in genes involved in bacterial invasion. These alterations could provide a mechanism by which PPIs predispose to CDI. ID NCT01901276.

Keywords: Acid Suppression; Clostridium difficile Infection; Gastroesophageal Reflux Disease; Pharmacology.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteria / classification
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Clostridioides difficile / drug effects
  • Clostridioides difficile / isolation & purification
  • Cross-Over Studies
  • Drug Administration Schedule
  • Enterocolitis, Pseudomembranous / chemically induced
  • Enterocolitis, Pseudomembranous / microbiology
  • Feces / microbiology
  • Healthy Volunteers
  • Humans
  • Intestines / drug effects*
  • Intestines / microbiology
  • Microbiota*
  • Omeprazole / administration & dosage*
  • Omeprazole / adverse effects
  • Proton Pump Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / adverse effects
  • Ribotyping
  • Risk Factors
  • Time Factors


  • Proton Pump Inhibitors
  • Omeprazole

Associated data