Research Spotlight: Migration of Microorganisms in the Gut as the Result of Long Term Use of Proton Pump Inhibitors

Hanseul Kim, PhD, a postdoctoral research fellow in the Division of Gastroenterology at Massachusetts General Hospital, is the lead author of a recently published research letter in the journal Gastroenterology, Altered Microbial Transcription in Long-Term Proton Pump Inhibitor Usage: Findings From a US Cohort Study

What Question Were You Investigating with Your Study?

Proton pump inhibitors (PPIs) are prescribed for suppression of stomach acid and are generally considered safe. They can help relieve symptoms of chronic acid reflux (GERD) and stomach ulcers. However, the impact of long-term usage of these medications is generally unknown.

Therefore, our study conducted a metatranscriptomic analysis to explore functional gene expression during the use of proton pump inhibitors, especially long-term usage.

What Methods Did You Use?

To investigate, we used stool metatranscriptome samples from a subpopulation of the long-running US prospective cohort, the Health Professionals Follow-up Study. Our study represents one of the first metatranscriptomic analyses during proton pump inhibitor usage. 

What Were Your Findings?

Our study observed that microorganisms typically found in oral sites tend to migrate to the gut with prolonged use of PPIs. Further analysis at the RNA level revealed that these migrated microorganisms could contribute to changes in the expression of biochemical pathways during extended use of proton pump inhibitors.

Our analysis of community-wide transcription suggests that long-term proton pump inhibitor use (≥6 years) can result in the altered expression of relevant biochemical pathways, which can be considered as a microbial response to adapt to a host selective pressure (i.e., medication-induced acid suppression).

What are the Next Steps?

Our analysis serves as a hypothesis-generating investigation, suggesting alterations in the expression of biochemical pathways. Further metatranscriptomic studies are required to confirm our findings.

Paper Cited:

Kim, H., Nzabarushimana, E., Huttenhower, C., Chan, A. T., & Nguyen, L. H. (2024). Altered Microbial Transcription in Long-term Proton Pump Inhibitor Use: Findings From a United States Cohort Study. Gastroenterology, S0016-5085(24)00309-3. Advance online publication. https://doi.org/10.1053/j.gastro.2024.03.026