title: Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Freedberg
authors.affiliation: New York Genome Center, New York, New York.
authors.forename: Nora C
authors.initials: NC
authors.lastname: Toussaint
authors.affiliation: College of Physicians and Surgeons, Columbia University Medical Center, New York, New York.
authors.forename: Sway P
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Columbia University Medical Center, New York, New York.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Whittier
authors.affiliation: Department of Medicine, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York; Department of Systems Biology, Columbia University, New York, New York. Electronic address: hw2429@cumc.columbia.edu.
authors.forename: Harris H
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York. Electronic address: ja660@cumc.columbia.edu.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Abrams
mesh_terms: D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016360:Clostridioides difficile / Q000187:drug effects / Q000302:isolation & purification; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004761:Enterocolitis, Pseudomembranous / Q000139:chemically induced / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D064368:Healthy Volunteers; D006801:Humans; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D064307:Microbiota; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D021521:Ribotyping; D012307:Risk Factors; D013997:Time Factors
chemical_list: D054328:Proton Pump Inhibitors; D009853:Omeprazole
keywords: Acid Suppression; Clostridium difficile Infection; Gastroesophageal Reflux Disease; Pharmacology