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P744 Proton pump inhibitors affect the gut microbiome

F. Imhann*1, M. J. Bonder2, A. Vich Vila1, J. Fu2, Z. Mujagic3, L. Vork3, E. F. Tigchelaar2, S. A. Jankipersadsing2, M. C. Cenit2, H. J. M. Harmsen4, G. Dijkstra1, L. Franke2, R. J. Xavier5, D. Jonkers3, C. Wijmenga2, R. K. Weersma1, A. Zhernakova2

1University of Groningen and University Medical Centre Groningen, Department of Gastroenterology and Hepatology, Groningen, Netherlands, 2University of Groningen and University Medical Centre Groningen, Department of Genetics, Groningen, Netherlands, 3Maastricht University Medical Centre+, Division Gastroenterology-Hepatology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, Netherlands, 4University of Groningen and University Medical Centre Groningen, Department of Medical Microbiology, Groningen, Netherlands, 5The Broad Institute of MIT and Harvard, Cambridge, United States


Proton pump inhibitors (PPI) are amongst 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 in both healthy individuals, inflammatory bowel disease (IBD) patients and irritable bowel syndrome (IBS) patients.


The gut microbiome composition of 1 815 individuals, spanning 3 cohorts containing healthy individuals, IBD patients and IBS patients, was assessed by tag-sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users vs non-users was analysed separately in each cohort, followed by a meta-analysis.


In total, 211 of the participants were using PPI 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 (FDR < 0.05). Multiple oral bacteria were overrepresented in the faecal microbiome of PPI users, including the genus Rothia (p = 9.8x1038). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus, and the potentially pathogenic species Escherichia coli, as well as a significant decrease in the genus Bifidobacterium and the family Ruminococcaceae.


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 compared with the effects of antibiotics or other commonly used drugs.