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Original article
Proton pump inhibitors alter the composition of the gut microbiota
  1. Matthew A Jackson1,
  2. Julia K Goodrich2,3,
  3. Maria-Emanuela Maxan4,
  4. Daniel E Freedberg5,
  5. Julian A Abrams5,
  6. Angela C Poole2,3,
  7. Jessica L Sutter2,3,
  8. Daphne Welter2,3,
  9. Ruth E Ley2,3,
  10. Jordana T Bell1,
  11. Tim D Spector1,
  12. Claire J Steves1
  1. 1Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
  2. 2Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA
  3. 3Department of Microbiology, Cornell University, Ithaca, New York, USA
  4. 4Clinical Age Research Unit, Kings College Hospital Foundation Trust, London, UK
  5. 5Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, New York, USA
  1. Correspondence to Dr Claire J Steves, Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas’ Hospital Campus, 3rd & 4th Floor South Wing Block D, Westminster Bridge Road, London SE1 7EH, UK; claire.j.steves{at}


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.

Design 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microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study.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.


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