Proton Pump inhibitors (drugs for GORD) alter the gut microbiome

While highly effective with a favourable safety profile, use of PPIs is not without concern. Since their introduction in the early 90s, PPI use has increased by more than 1000% in Australia,2 with over 19 million prescriptions in the 2013–14 financial year.1 Over the last decade, at least two PPIs have featured in the top 10 most prescribed PBS-subsidised medicines every year.1,9 Not surprisingly, there is growing international concern over their increasing use.2,10 Long-term use is only recommended in selected populations11,12 but data indicate that this accounts for most of the total use.10 Several studies suggest that a substantial proportion of PPI users do not have a clear indication for therapy

Some reports have linked PPI use to increased risk of fractures, pneumonia, enteric infections, vitamin and mineral deficiencies, and acute interstitial nephritis.5,19 Although the absolute risk is very low, many of the patients in these reports were older people – a group that makes up the largest proportion of PPI users 2 and who are at increased risk of medicine-related problems.20 (source:



We are beginning to build a picture of how important the microbiome (our symbiotic bacteria population that lives mostly in our gut) is to our health. Scientists are  still learning  how these tiny creatures affect our immunity, our digestion, our bowel movements, and our nervous system. But despite there being a lot we don’t know there is no doubt we can’t live without them and altering this environment can deteriorate  our health or improve our health. The study below concludes that the gut microbiome in people who regularly took PPIs was less healthy than in people who did not use PPIs. This could explain the associations between PPIs use and increase occurrence of enteric infections specifically the clostridium difficile infections that causes diarrhea.

Looking at the statistics for prescriptions in Australia this is a vast number of people.


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.


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.


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.


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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