Medications can continue to shape the gut microbiome long after treatment stops, according to a large analysis led by researchers at the University of Tartu Institute of Genomics. The gut microbiome, the vast community of microorganisms in the digestive tract, can influence digestion, metabolism, immunity, and broader health outcomes.
Drug effects on the gut microbiome may persist
Investigators examined stool samples and prescription records from more than 2,500 participants in the Estonian Biobank who were enrolled in the Estonian Microbiome cohort. They reported that most medications assessed were linked to measurable differences in the gut microbiome, and for many drugs those differences were still evident years after use had ceased.
These lasting signatures were not confined to antibiotics, which are already known to disrupt gut bacteria. Antidepressants, beta-blockers, proton pump inhibitors, and benzodiazepines were each associated with distinctive microbial patterns. Beta-blockers are widely used for high blood pressure and certain cardiac conditions. Proton pump inhibitors reduce stomach acid to manage acid reflux and related disorders. Benzodiazepines are prescribed for anxiety and other conditions.
The lead author, Dr. Oliver Aasmets, said most microbiome research accounts only for current medications, yet the team found that past drug exposure can be a strong driver of individual microbiome differences. The results indicate that studies probing links between the microbiome and disease may need to factor in treatments taken months or even years earlier.
Anxiety medications show notable microbiome impacts
A key result involved benzodiazepines, commonly used for anxiety. Their associations with gut microbial profiles were comparable to those seen with broad-spectrum antibiotics, which act on many bacterial types and can markedly reshape the gut community.
The analysis also showed that drugs within the same class did not always have similar microbiome effects. For instance, diazepam and alprazolam, which may be prescribed for similar indications, differed in how strongly they appeared to disrupt gut microbes. This suggests that grouping medications only by class can mask drug-specific influences, and that individual agents may need to be evaluated separately in microbiome research.
Follow-up sampling links medication changes to microbial shifts
Follow-up stool samples from a smaller subset of participants allowed researchers to observe what happened when people began or discontinued certain therapies. These time-point comparisons revealed predictable shifts in gut microbes that tracked with changes in medication use, supporting the idea that the drugs themselves contribute to at least some of the observed differences.
Despite the smaller number of participants in this longitudinal component, the team confirmed persistent associations tied to proton pump inhibitors, selective serotonin reuptake inhibitors, and antibiotics, including penicillins in combination and macrolides. Selective serotonin reuptake inhibitors are a widely used class of antidepressants, and macrolides are antibiotics used to treat a range of bacterial infections.
Medication history is critical in gut microbiome research
The findings add to evidence that the gut microbiome reflects more than current diet, lifestyle, health status, and active prescriptions. Prior treatments can leave detectable biological traces long after a course of therapy ends. Corresponding author Professor Elin Org described the work as a comprehensive, real-world assessment of long-term medication effects using medical records, and encouraged researchers and clinicians to incorporate medication histories when interpreting microbiome data.
Accounting for past drug exposure may help distinguish microbiome patterns associated with disease from those shaped by prior treatments, improving the accuracy of studies that link microbial changes to health outcomes.
For readers interested in how regulators approach drug safety and access, related reporting includes the analysis of an FDA peptides advisory and its potential impact on unapproved therapies. Ongoing research from institutions such as the University of Tartu and global health agencies, including the World Health Organization, continues to explore how medications intersect with the human microbiome.