Proton pump inhibitors (PPIs) do not have a large effect on microbial diversity of the colon, but do affect specific taxa, including Streptococcaceae and Enterococcaceae, which mediate resistance to Clostridium difficile infection (CDI), researchers report in the October issue of Gastroenterology. This finding might provide a mechanism by which these drugs increase risk for CDI.
PPIs have been associated with CDI, but the mechanisms of this association are unclear. Broad-spectrum antibiotics, which reduce diversity in the intestinal microbiome, are the most important risk factor for CDI. Increases in Enterococcaceae and decreases in Clostridial taxa have also been associated with increased risk for CDI.
Daniel E. Freedberg et al conducted an open-label crossover trial to test whether proton pump inhibitors, given in the absence of antibiotics, alter the human colonic microbiome. Fecal samples were collected at 2 baseline time points (4 weeks apart, to exclude inter-individual differences). Subjects were then assigned to groups that received either 4 or 8 weeks of PPI (40 mg omeprazole, twice daily) and fecal samples were collected.
Using 16S ribosomal RNA gene sequencing analyses, Freedberg et al found significant changes during PPI use in taxa associated with CDI (increased Enterococcaceae and Streptococcaceae, decreased Clostridiales) and taxa associated with gastrointestinal bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae).
In a functional analyses, there were no changes in bile acids while the patients took PPIs, but there were changes in expression of genes involved in bacterial invasion.
In an editorial that accompanies the article, Silvia Melgar and Max Nieuwdorp state that the finding that the intestinal microbiota are affected by PPIs in healthy individuals indicates the widespread effects of daily acid suppression. Regular usage of drugs such as PPIs and statins might make our intestine more vulnerable to pathogen colonization. They propose mechanisms by which PPIs might alter specific bacterial taxa.
Melgar and Nieuwdorp propose that identification of a PPI-induced microbe profile associated with CDI may pave the way for therapies such as dietary interventions, probiotics, antimicrobial agents, vaccination, and fecal microbiota transplantation.