Medications used many years earlier can still influence the human gut microbiome, according to a large-scale study conducted by the University of Tartu Institute of Genomics.
Researchers examined stool samples and prescription records from more than 2,500 participants in the Estonian Biobank’s Microbiome cohort and discovered that most medications tested were associated with shifts in gut microbes.
Many of these changes persisted for years after patients had stopped taking the drugs. The influence was not confined to antibiotics; antidepressants, beta-blockers, proton pump inhibitors, and benzodiazepines also left lasting microbial “fingerprints.”
Importance of medication history in microbiome research
“Most microbiome studies only consider current medications, but our results show that past drug use can be just as important as it is a surprisingly strong factor in explaining individual microbiome differences,” said Dr. Oliver Aasmets, lead author. This highlights that it is critical to account for drug usage history when studying links between the microbiome and disease.
Surprisingly, benzodiazepines, which are commonly prescribed to treat anxiety, were found to influence the gut microbiome to a degree similar to broad-spectrum antibiotics. The study also revealed that medications within the same drug class, such as diazepam and alprazolam, can vary in the extent to which they disturb microbial communities.
Confirmed long-term microbial shifts
Follow-up samples from a subset of participants confirmed that starting or stopping certain drugs caused predictable microbial shifts, suggesting causal effects. Despite the small sample size of the second time-point analysis, the authors were able to verify long-term effects of proton pump inhibitors, selective serotonin reuptake inhibitors, and antibiotics, such as penicillins in combination and macrolides.
“This is a comprehensive systematic evaluation of long-term medication effects on the microbiome using real-world medical health records,” said Professor Elin Org, corresponding author. “We hope this encourages researchers and clinicians to factor in medication history when interpreting microbiome data.”
Reference: “A hidden confounder for microbiome studies: medications used years before sample collection” by Oliver Aasmets, Nele Taba, Kertu Liis Krigul, Reidar Andreson, Estonian Biobank Research Team and Elin Org, 5 September 2025, mSystems.
DOI: 10.1128/msystems.00541-25
This work was funded by the Estonian Research Council grant PRG1414 (to E.O.), the EMBO Installation grant 3573 (to E.O.), and the Biocodex Microbiota Foundation research grant (to E.O.). E.O. was additionally supported by Estonian Center of Genomics/Roadmap II project No. 16-0125.
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