Non-antibiotic medications leave lasting mark on gut microbiome, even years after use (Sep 2025) A hidden confounder for microbiome studies: medications used years before sample collection Other 

Michael Harrop

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https://medicalxpress.com/news/2025-09-medications-gut-microbiome-years.html
https://journals.asm.org/doi/10.1128/msystems.00541-25

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

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.

ABSTRACT​

Medication usage is a known contributor to the inter-individual variability of the gut microbiome. However, medications are often used repeatedly and for long periods, a notion yet unaccounted for in microbiome studies. Recently, we and others showed that not only the usage of antibiotics and antidepressants at sampling, but also past consumption, is associated with the gut microbiome. This effect can be “additive”—the more a medication is used, the stronger the impact on the microbiome.

Here, by utilizing retrospective medication usage data from the electronic health records and the observational Estonian microbiome cohort shotgun metagenomics data set (n = 2,509), we systematically evaluate the long-term effects of antibiotics and human-targeted medications on the gut microbiome. We show that past usage of medications is associated with the gut microbiome. For example, the effects of antibiotics, psycholeptics, antidepressants, proton pump inhibitors, and beta-blockers are detectable several years after use. Furthermore, by analyzing a subcohort (n = 328) with a second microbiome characterization, we show that similar changes in the gut microbiome occur after treatment initiation or discontinuation, possibly indicating causal effects.

IMPORTANCE​

This is the first study using detailed retrospective medication usage data from electronic health records to systematically assess the long-term effects of medication usage on the gut microbiome. We identified carryover and additive effects on the gut microbiome for a range of antibiotics and non-antibiotic medications, such as benzodiazepine derivatives, antidepressants and glucocorticoids, among others. These findings highlight a collateral effect of diverse drug classes on the gut microbiome, which warrants accounting for long-term medication usage history when assessing disease-microbiome associations.
 
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