Proton pump inhibitors affect the microbiome

Proton pump inhibitors (PPI) are used to reduce gastric acid production in individuals’ guts and are prescribed to treat ulcers, gastroesophogeal reflux disease (GERD), and other conditions associated with acid production. It is one of the most commonly used drugs in the world. We know (and have written about) that PPIs are associated with increased intestinal infections, specifically Clostridium difficile, and the gut microbiome plays an important role in infections of the intestine. A recent study looked at the influence that PPIs had on the gut microbiome.

The team of researchers studied the gut microbiome of 1815 individuals. They looked at PPI users vs non-users. Of those sampled, 215 of them were taking a PPI at the time that a sample was taken. It was found that those taking the PPIs had lower microbial diversity compared to those not taking PPIs. They also found that bacteria usually found in the mouth was over-represented in the fecal samples of those taking PPIs, including those in the Rothia genus. They also observed an increase in Enterococcus, Streptococcus, Staphylococcus, and Escherichia coli, a potentially pathogenic bacterium.

PPI usage effects are more prominent than those of most other drugs, including antibiotics. The results of this study are consistent with a less healthy microbiome and allow us to better understand why PPIs may lead to an increase of susceptibility to intestinal infections like C. diff.

Proton pump inhibitors may increase susceptibility to Clostridium difficile infection

Individuals who produce too much gastric acid in their stomach are often are prescribed proton pump inhibitors (PPIs), a group of drugs that prevent the production of acid for the treatment of ulcers, gastroesophogeal reflux disease (GERD), and other conditions related to acid production. Scientists at the Mayo Clinic in Arizona and Minnesota published a study last week in the journal Microbiome that found that the prolonged use of PPIs resulted in a reduction in gut microbiome diversity. The authors hypothesized that this reduced gut diversity is predisposing patients using PPIs to Clostridium difficile infection, an often-fatal bacterial infection that we have written about extensively on the blog.

Previous observational studies had shown a correlation between PPI usage and C. diff infection, however this study set out to identify what was actually causing this link.  The scientists took fecal samples from 9 healthy subjects before, during, and after they were given either a high or low-dose PPI treatment. They also took fecal samples from 5 patients with untreated C. diff infections and compared the bacteria in the fecal samples between the healthy patients and untreated patients infected with C. diff.

After taking PPIs, the healthy individuals’ gut microbiomes started looking very similar to those of patients with untreated C. diff. The number of bacterial species was significantly reduced from before they were exposed to PPIs, and the reduction was independent of dosage. This reduction of bacterial diversity in the gut doesn’t mean that patients on these medications will definitely become infected with C. diff, but it does likely predispose patients to the infection and more easily allow the bacteria to colonize the gut. 

The study found that after 28 days of PPI treatment the reduced gut diversity can be reversed, however it is not clear what prolonged PPI usage does to the gut microbiome.  This study included only a small number of subjects and future studies will hopefully be expanded and include patients who are prescribed PPIs for treating a specific condition. Better understanding the impact that PPIs have on the gut microbiome may also allow for the development of probiotics that could help counteract the effects of PPIs and help keep the gut microbiome diversity stable.