Medications leave lasting mark on gut microbiome, even years after use

Medications taken years ago can continue to shape the human gut microbiome, according to a large-scale study from the University of Tartu Institute of Genomics.

Analyzing stool samples and prescription records from over 2,500 Estonian Biobank participants in the Estonian Microbiome cohort, researchers found that the majority of drugs studied were linked to microbiome changes, with a substantial number of them also showing long-term effects detectable years after patients stopped taking them.

The impact was not limited to antibiotics: antidepressants, beta-blockers, proton pump inhibitors, and benzodiazepines all left microbial “fingerprints.”

“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. The research is published in the journal mSystems.

Interestingly, benzodiazepines—commonly prescribed for anxiety—had microbiome effects comparable to broad-spectrum antibiotics. The results also show that drugs from the same class that might be used for the same condition, e.g. diazepam and alprazolam, may differ in how much they disrupt the microbiome.

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.”