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PPIs impact specific gut microbiota associated with C. difficile infection
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Researchers observed significant changes in gut microbiota that are associated with Clostridium difficile infection and gastrointestinal bacterial overgrowth in participants using proton pump inhibitors in a small crossover study.
“The mechanism linking proton pump inhibitors with increased risk for C. difficile infection is uncertain,” Daniel E. Freedberg, MD, from the division of digestive and liver diseases at Columbia University Medical Center, told Healio Gastroenterology. “We conducted a small, open-label crossover study to test whether PPIs increase risk for CDI by altering fecal microbiota.”
Daniel E. Freedberg
Freedberg and colleagues collected fecal samples donated by 12 healthy volunteers at baseline and 4 weeks, after which they took 40-mg Prilosec (omeprazole, AstraZeneca) twice daily for 4 weeks and then donated additional fecal samples. Six participants then continued taking the PPIs for an additional 4 weeks, and at week 12, fecal samples were collected again from all participants. All samples were analyzed using 16S ribosomal RNA gene sequencing.
“After 4 to 8 weeks of high-dose PPIs, we found no changes in the overall diversity of the fecal microbiome,” Freedberg said. “However, specific bacteria taxa that have been associated with CDI, including Streptococcaceae and Enterococcaceae, were increased after PPIs. This could provide a mechanism by which PPIs predispose to CDI.”
They also observed decreased Clostridiaceae, and changes in taxa associated with gastrointestinal bacterial overgrowth, including Micrococcaceae and Staphylococcaceae. Additionally, a functional analysis showed that during PPI use there was no change in bile acids, but an increase in genes involved in bacterial invasion.
“PPIs may increase risk for CDI by altering crucial taxa involved in colonization resistance to C. difficile,” the researchers concluded.
“Although there are some methodologic shortcomings of the current trial that might have severely impacted results (eg, no dietary intake monitoring, use of relatively high daily PPI doses), the fact that even in healthy subjects the intestinal microbiota are affected by PPI underscores the drastic effects of daily acid suppression on our intestinal bacteria,” Silvia Melgar, PhD, from the APC Microbiome Institute, and Max Nieuwdorp, MD, PhD, from the department of internal medicine at the Academic Medical Center in Amsterdam, wrote in an accompanying editorial. “Moreover, these data provide evidence that regular usage of orally administered drugs (eg, PPI and statins) might affect gut microbiota composition, thus rendering our intestine more vulnerable for pathogen colonization including C. difficile.” – by Adam Leitenberger
Disclosures: The researchers report no relevant financial disclosures. Melgar reports she and the APC Microbiome Institute receive financial support from Science Foundation Ireland. Nieuwdorp reports he is supported by a ZONMW-VIDI grant.
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