title: Proton pump inhibitors affect the gut microbiome.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome.
  
  
  METHODS
  The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis.
  
  
  RESULTS
  211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli.
  
  
  CONCLUSIONS
  The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Imhann
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Marc Jan
authors.initials: MJ
authors.lastname: Bonder
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Arnau
authors.initials: A
authors.lastname: Vich Vila
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fu
authors.affiliation: Maastricht University Medical Center+, Division Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
authors.forename: Zlatan
authors.initials: Z
authors.lastname: Mujagic
authors.affiliation: Maastricht University Medical Center+, Division Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
authors.forename: Lisa
authors.initials: L
authors.lastname: Vork
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Ettje F
authors.initials: EF
authors.lastname: Tigchelaar
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Soesma A
authors.initials: SA
authors.lastname: Jankipersadsing
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Cenit
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Medical Microbiology, Groningen, The Netherlands.
authors.forename: Hermie J M
authors.initials: HJ
authors.lastname: Harmsen
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.affiliation: Broad Institute of Harvard and MIT, Boston, Massachusetts, USA.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Maastricht University Medical Center+, Division Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands.
authors.forename: Daisy
authors.initials: D
authors.lastname: Jonkers
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands.
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
mesh_terms: D000328:Adult; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000494:pharmacology*
chemical_list: D054328:Proton Pump Inhibitors
keywords: ENTERIC INFECTIONS; INTESTINAL BACTERIA; PROTON PUMP INHIBITION