Medications Can Alter Gut Microbiome for Years After Use, Study Finds

A large study led by researchers at the University of Tartu Institute of Genomics in Estonia has found that medications can influence gut microbes long after a person stops taking them. The gut microbiome — bacteria and other microorganisms in the digestive tract — affects digestion, metabolism and immune function. Researchers analyzed stool samples and prescription records from more than 2,500 participants in the Estonian Biobank's Microbiome cohort and found that most medications examined were associated with differences in the gut microbiome. For many drugs, those differences could still be detected years after people stopped taking them.

The lasting effects were not limited to antibiotics, already known for disrupting gut bacteria. Antidepressants, beta-blockers, proton pump inhibitors (PPIs) and benzodiazepines were also linked to distinctive microbial "fingerprints." Beta-blockers treat high blood pressure and heart problems; PPIs reduce stomach acid for acid reflux; benzodiazepines are used for anxiety. "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, noting most studies consider only current medications.

One striking finding involved benzodiazepines: their gut microbiome associations were comparable to broad-spectrum antibiotics, which act against many bacteria types. Drugs in the same class did not necessarily affect the microbiome the same way — diazepam and alprazolam differed in how strongly they disrupted gut microbes, suggesting individual drugs may need separate consideration rather than being grouped by class.

Researchers also examined follow-up stool samples from a smaller group, observing predictable shifts in gut microbes when people started or stopped medications — evidence the medications themselves were responsible for some differences. They confirmed persistent effects linked to PPIs, SSRIs (a widely used antidepressant class), 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."