Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility

Charlie T Seto, Patricio Jeraldo, Robert Orenstein, Nicholas Chia, John K DiBaise

The role of the gut microbiome in arresting pathogen colonization and growth is important for protection against Clostridium difficile infection (CDI). Observational studies associate proton pump inhibitor (PPI) use and CDI incidence. We hypothesized that PPI use affected the distal gut microbiome over time, an effect that would be best explored by time-longitudinal study of healthy subjects on PPI in comparison to treatment-naïve CDI subjects. This study enrolled nine healthy human subjects and five subjects with treatment-naïve CDI. After random assignment to a low (20 mg/day) or high (2× 20 mg/day) dose group, fecal samples were collected from the nine healthy subjects before, during, and after 28 days of PPI use. This was done in conjunction with pre-treatment fecal collection from CDI subjects. High-throughput sequencing (16S rRNA) was performed on time-longitudinal samples to assess changes to the healthy gut microbiome associated with prolonged PPI usage. The healthy samples were then compared to the CDI subjects to explore changes over time to the gut microbiome associated with PPI use and potentially related to CDI.