Summary:
This study examined whether medications taken for long periods can leave lasting effects in the gut microbiome. Although the microbiome is known to reflect current health, diet, lifestyle and recent drug exposure, emerging evidence suggests that past medication use may also shape microbial composition. Prior work has shown that antibiotics taken more than six months earlier can still influence microbiome structure, and that repeated exposures may have cumulative effects. Similar results have been reported for antidepressants, beta‑blockers and proton pump inhibitors. To investigate these long‑term effects, this study used metagenomic profiles from more than 2,500 adults with detailed retrospective medication histories from electronic health records. A subset of participants also provided a second stool sample several years later, enabling evaluation of microbiome changes following treatment initiation or discontinuation. The results showed that past medication use was consistently associated with differences in gut microbial composition. Long‑term effects were detectable for multiple drug classes, including antibiotics, psycholeptics, antidepressants, proton pump inhibitors and beta‑blockers, with stronger associations observed in individuals with higher cumulative exposure. Overall, this observational study demonstrates that many commonly used medications exert long‑lasting effects on the gut microbiome. These findings highlight that drug exposures may contribute to persistent alterations in gut microbial ecology.
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Abstract:
Medication usage is a known contributor to the inter-individual variability of the gut microbiome. However, medications are often used repeatedly and for long periods, a notion yet unaccounted for in microbiome studies. Recently, we and others showed that not only the usage of antibiotics and antidepressants at sampling, but also past consumption, is associated with the gut microbiome. This effect can be “additive”—the more a medication is used, the stronger the impact on the microbiome. Here, by utilizing retrospective medication usage data from the electronic health records and the observational Estonian microbiome cohort shotgun metagenomics data set (n = 2,509), we systematically evaluate the long-term effects of antibiotics and human-targeted medications on the gut microbiome. We show that past usage of medications is associated with the gut microbiome. For example, the effects of antibiotics, psycholeptics, antidepressants, proton pump inhibitors, and beta-blockers are detectable several years after use. Furthermore, by analyzing a subcohort (n = 328) with a second microbiome characterization, we show that similar changes in the gut microbiome occur after treatment initiation or discontinuation, possibly indicating causal effects.
Article Publication Date: 05/09/2025
DOI: 10.1128/msystems.00541-25
