“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 of the study. The findings underscore the importance of considering a person’s medication history when exploring connections between gut microbes and disease.

Interestingly, benzodiazepines — commonly prescribed for anxiety — produced microbiome alterations similar to those seen with broad-spectrum antibiotics. The study also revealed that drugs within the same category, such as diazepam and alprazolam, can vary in how much they disturb gut microbial balance.

Follow-up samples from a smaller group of participants showed that starting or discontinuing specific medications led to predictable shifts in gut microbes, supporting a likely cause-and-effect relationship. Although this second phase involved fewer samples, the researchers confirmed persistent effects from proton pump inhibitors, selective serotonin reuptake inhibitors, and several antibiotics, including 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, the study’s corresponding author. “We hope this encourages researchers and clinicians to factor in medication history when interpreting microbiome data.”