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

doi:10.1186/2049-2618-2-42

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

Microbiome. 2014 Nov 25:2:42. doi: 10.1186/2049-2618-2-42. eCollection 2014.

Authors

Charlie T Seto¹, Patricio Jeraldo², Robert Orenstein³, Nicholas Chia⁴, John K DiBaise⁵

Affiliations

¹ Biomedical Informatics and Computational Biology, University of Minnesota-Rochester, Rochester, MN, USA ; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
² Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA ; Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
³ Division of Infectious Diseases, Mayo Clinic, Scottsdale, AZ, USA.
⁴ Biomedical Informatics and Computational Biology, University of Minnesota-Rochester, Rochester, MN, USA ; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA ; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA ; Division of Surgery Research, Mayo Clinic, Rochester, MN, USA ; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
⁵ Division of Gastroenterology, Mayo Clinic, Scottsdale, AZ, USA.

Abstract

Background: 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.

Results: We report that PPI usage at low and high dosages, administered for 28 days, resulted in decreases to observed operational taxonomic unit (OTU) counts after both 1 week and 1 month. This decrease resulted in observed OTU levels that were similar to those found in treatment-naïve CDI patients, which was partly reversible after a 1 month recovery period. We did not detect a dose-dependent difference in OTU levels nor did we detect significant changes in taxa previously reported to be affected by PPI treatment.

Conclusion: While our observation of diminishing observed OTU counts during PPI therapy is a preliminary finding in a small cohort, our hypothesis that PPIs disrupt the healthy human gut microbiome is supported in this group. We conclude that decreases in observed species counts were reversible after cessation of PPI usage within 1 month. This finding may be a potential explanation for the association between prolonged PPI usage and CDI incidence.

Keywords: Clostridium difficile; Gut microbiome; Proton pump inhibitor.

Grants and funding

R01 CA179243/CA/NCI NIH HHS/United States