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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 149; no. 4; pp. 883 - 885.e9
• Main Authors: Freedberg, Daniel E, Toussaint, Nora C, Chen, Sway P, Ratner, Adam J, Whittier, Susan, Wang, Timothy C, Wang, Harris H, Abrams, Julian A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015
• Subjects: Acid Suppression; Bacteria - classification; Bacteria - drug effects; Bacteria - genetics; Bacteria - isolation & purification; Clostridium difficile - drug effects; Clostridium difficile - isolation & purification; Clostridium difficile Infection; Cross-Over Studies; Drug Administration Schedule; Enterocolitis, Pseudomembranous - chemically induced; Enterocolitis, Pseudomembranous - microbiology; Feces - microbiology; Gastroenterology and Hepatology; Gastroesophageal Reflux Disease; Healthy Volunteers; Humans; Intestines - drug effects; Intestines - microbiology; Microbiota; Omeprazole - administration & dosage; Omeprazole - adverse effects; Pharmacology; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - adverse effects; Ribotyping; Risk Factors; Time Factors; Acid Suppression; Gastroesophageal Reflux Disease; PPI; CDI; Pharmacology; proton pump inhibitor; Clostridium difficile Infection
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2015.06.043

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. ClinicalTrials.gov ID NCT01901276.