Common Medications May Alter Our Gut Microbiome for Years

By Wayne Persky

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Scientists from the University of Tartu in Estonia studied over 2,500 Estonian Biobank samples and found that drugs we took years (sometimes many years) ago can still be detected in our gut microbiome today (Aasmets, Taba, Krigul, Andreson, and Org, 2025).1 And it’s not just antibiotics. Antidepressants, beta-blockers, proton-pump inhibitors (PPIs), and benzodiazepines leave distinct microbial fingerprints, some comparable to the impact of broad-spectrum antibiotics. That means a person’s medication history is a hidden confounder that microbiome researchers (and clinicians) have been overlooking in their work.

Does that list of medications look familiar?

It should, because it includes many of the medications that some of us have blamed for the development of our microscopic colitis (MC).

This study considered long-term medication effects.

The research team used shotgun sequencing to analyze 2,509 stool samples from the Estonian Biobank Microbiome cohort, linking each sample to years of electronic prescription records. A smaller cohort (328) from the same original 2,509 samples were used as second samples to see what happens when people start or stop specific drugs.​

Shotgun sequencing involves DNA sequencing by breaking a large DNA molecule into millions of smaller, random fragments, sequencing the fragments independently, and then using computer algorithms to reassemble these fragments into their original order by identifying overlapping sections. By utilizing this process, scientists can determine the complete sequence of long DNA strings, such as an entire genome.

Up until now, at least, most human microbiome studies only control for current medications. This study explicitly modeled past use, allowing the team to test for carryover (lingering) and additive (cumulative) drug effects on the microbiome.

The study found that:

1. Medication echoes are common and long-lived.
Prior use of several drug classes, including antibiotThe study found that:ics, psycholeptics (notably benzodiazepines), antidepressants, PPIs, and beta-blockers, was associated with persistent shifts in microbiome composition years after the last prescription. In media summaries of the work, the authors note that nearly half of the assessed drugs still showed microbiome associations more than a year after use.

2. Benzodiazepines stood out.
Surprisingly, benzodiazepines produced alterations on par with broad-spectrum antibiotics, and different drugs within the same class (for example, diazepam compared with alprazolam) showed unequal microbiome disruption. That heterogeneity matters: “which benzo” or “which SSRI” could leave different long-term microbial signatures (Estonian Research Councilm 2025, October 9).2

3. There are additive effects.
The more often (or longer) a medication was used in the past, the stronger its detectable microbiome impact — evidence for dose–history relationships, not mere coincidence.

4. Direction of effect (causality) gets support from follow-up samples.
In the smaller subset, starting or discontinuing certain meds led to predictable shifts in specific microbes (for example, with PPIs, SSRIs, and several antibiotic classes), strengthening a cause-and-effect interpretation. (It’s not a randomized trial, but the within-person changes are compelling.)

How can non-antibiotics drugs do this?

This study result joins a growing body of literature showing that many human-targeted (non-antibiotic) drugs have direct antimicrobial activity or change the gut environment (for example, gastric pH, motility, bile acids) in ways that reshape the microbiome. In vitro screens have found that 24% of tested non-antibiotic drugs inhibit gut bacterial strains, and newer studies show such drugs can weaken colonization resistance against pathogens (Maier, et al., 2018).i The Estonian data extend those insights to real-world, long-term human outcomes

The bottom line.

The Estonian Biobank study makes a clear case: our microbiomes carry long-lasting imprints of medications — antibiotics and many others. For researchers, past prescriptions are a hidden confounder that must be accounted for. For clinicians and patients, the work encourages thoughtful use and periodic re-evaluation of long-term medications, recognizing that the gut ecosystem may remember them long after we do.

References

1. Aasmets, O., Taba, N., Krigul, K. L., Andreson, R., and Org, E. 0. (2025). A hidden confounder for microbiome studies: medications used years before sample collection. mSystems 0:e00541-25. Retrieved from https://journals.asm.org/doi/10.1128/msystems.00541-25

2. Estonian Research Council. (2025, October 9). "Common medications may secretly rewire your gut for years." ScienceDaily, <www.sciencedaily.com/releases/2025/10/251008030953.htm>. Retrieved from https://www.sciencedaily.com/releases/2025/10/251008030953.htm

3. Maier, L., Pruteanu, M., Kuhn, M., Zeller, G., Telzerow, A., Anderson, E. E., . . Typas, A. (2018). Extensive impact of non-antibiotic drugs on human gut bacteria. Nature, 555(7698). pp 623–628. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29555994/