title: Proton pump inhibitors alter the composition of the gut microbiota.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort.
  
  
  METHODS
  We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study.
  
  
  RESULTS
  We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut.
  
  
  CONCLUSIONS
  Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Matthew A
authors.identifier: http://orcid.org/0000-0002-7891-6217
authors.initials: MA
authors.lastname: Jackson
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA Department of Microbiology, Cornell University, Ithaca, New York, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Goodrich
authors.affiliation: Clinical Age Research Unit, Kings College Hospital Foundation Trust, London, UK.
authors.forename: Maria-Emanuela
authors.initials: ME
authors.lastname: Maxan
authors.affiliation: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Freedberg
authors.affiliation: Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Abrams
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA Department of Microbiology, Cornell University, Ithaca, New York, USA.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Poole
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA Department of Microbiology, Cornell University, Ithaca, New York, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sutter
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA Department of Microbiology, Cornell University, Ithaca, New York, USA.
authors.forename: Daphne
authors.initials: D
authors.lastname: Welter
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA Department of Microbiology, Cornell University, Ithaca, New York, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Jordana T
authors.initials: JT
authors.lastname: Bell
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Steves
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D041742:Upper Gastrointestinal Tract; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors
keywords: GASTRIC ACID; INTESTINAL MICROBIOLOGY; LACTIC ACID BACTERIA; LACTOBACILLUS; PROTON PUMP INHIBITION