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Original article
Proton pump inhibitors affect the gut microbiome
  1. Floris Imhann1,
  2. Marc Jan Bonder2,
  3. Arnau Vich Vila1,
  4. Jingyuan Fu2,
  5. Zlatan Mujagic3,
  6. Lisa Vork3,
  7. Ettje F Tigchelaar2,
  8. Soesma A Jankipersadsing2,
  9. Maria Carmen Cenit2,
  10. Hermie J M Harmsen4,
  11. Gerard Dijkstra1,
  12. Lude Franke2,
  13. Ramnik J Xavier5,
  14. Daisy Jonkers3,
  15. Cisca Wijmenga2,
  16. Rinse K Weersma1,
  17. Alexandra Zhernakova2
  1. 1University of Groningen and University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands
  2. 2University of Groningen and University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands
  3. 3Maastricht University Medical Center+, Division Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands
  4. 4University of Groningen and University Medical Center Groningen, Department of Medical Microbiology, Groningen, The Netherlands
  5. 5Broad Institute of Harvard and MIT, Boston, Massachusetts, USA
  1. Correspondence to Prof Dr Rinse K Weersma, Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, Groningen 9700 RB, The Netherlands; r.k.weersma{at}


Background and aims 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.


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