October 14, 2025, 8:18 am | Read time: 6 minutes
Many people regularly take medications, but what many don’t know is that some of these drugs can leave measurable traces in the body years after the last dose—especially in the gut microbiome. A new long-term study from Estonia shows that not only antibiotics but also commonly prescribed medications such as antidepressants, blood pressure medications, or tranquilizers can sustainably alter the microbial balance in the gut. These previously underestimated long-term effects could have far-reaching consequences—for the evaluation of health data, for diagnoses and therapies, and for research on gut flora. FITBOOK editor Julia Freiberger explains what the new study shows in detail—and why medication history should play a larger role in the future.
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The Study: Data, Design, and Method
The research team led by Oliver Aasmets and Elin Org from the University of Tartu used data from the Estonian Microbiome Cohort (EstMB)—a large-scale population study conducted with the help of the Estonian Biobank.
A total of 2,509 adults between the ages of 23 and 89 were examined. They all provided stool samples, which were analyzed in the lab using a method called shotgun metagenomics. This is a particularly precise form of genetic analysis: Not only individual bacterial species are recorded, but the entire genome of all microorganisms in the stool. This allows for a very accurate determination of which species are present in the gut, how frequently they occur, and how the composition differs between different people.
In addition, complete electronic health data were available for all participants—including information on diseases, lifestyle, body measurements, and all prescription medications they had received in the five years before the sample was taken. This comprehensive data foundation allowed researchers to systematically investigate whether medications have a long-term impact on the microbiome—and if so, how strong this impact is.
A subgroup of 328 participants provided a second stool sample after about four and a half years. This second sampling was particularly valuable for measuring changes in the microbiome over time—such as after starting or stopping a medication.1
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Four Central Research Questions
The study was divided into four main areas:
- How does the current intake of a medication affect the microbiome?
- Are there long-term effects—meaning measurable changes even if the medication was discontinued years ago?
- Do the effects intensify if a medication is taken over a longer period or multiple times?
- What changes occur in the microbiome when a medication is started or stopped?
For each of these questions, the scientists conducted extensive statistical analyses—including regression models, scatter analyses, and model comparisons, always considering possible confounding factors such as age, gender, body weight, diseases, lifestyle, and the intake of other medications.
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Medications Last Longer Than Thought
The results are clear:
- Of the 186 medications analyzed, 167—about 90 percent—showed a significant impact on the gut microbiome.
- In 78 cases—about 42 percent—this effect was still measurable even if the medication had last been taken more than three years ago.
This Was Especially the Case with These Medications:
- Antibiotics (e.g., macrolides, penicillins)
- Antidepressants
- Benzodiazepines (e.g., diazepam, alprazolam)
- Beta-blockers
- Proton pump inhibitors (PPIs)
A key measure in microbiome research is the so-called alpha diversity—the diversity of microorganisms living in the gut. This diversity was significantly reduced in many former medication users, even if the intake was more than four years ago.
Additionally, an additive effect was observed: The more frequently a particular medication had been prescribed in the past, the more pronounced the observable change in the microbiome. This correlation was particularly evident with blood pressure medications, glucocorticoids, and tranquilizers.
Second Measurement Confirms Long-term Effects
The participants with two samples provided additional insights: If a medication was newly taken between the two time points, the microbiome also changed—often in the same direction as already observed in the first group. Conversely, it was also shown that discontinuing a medication could lead to an opposite development.
Some medications, such as the tranquilizer alprazolam, had stronger effects on the microbiome than some antibiotics. Even within the same class of drugs—such as proton pump inhibitors or benzodiazepines—there were significant differences in effect. This suggests that medications with similar purposes can indeed interfere with the bacterial balance of the gut to varying degrees.
What Does This Mean for Medicine and Research?
The study has several far-reaching implications:
Long-term Effects Must Be Considered in Studies
Until now, microbiome studies have mostly only asked about current medication intake. However, the new data show that even medications taken years ago can still affect the microbiome—and thus potentially skew study results.
Not Only Antibiotics Are Relevant
It is known that antibiotics kill bacteria. However, it is surprising that many other medications—such as antidepressants or blood pressure medications—can also change the composition of the gut flora. Some act similarly to antibiotics.
Therapy Decisions Could Be Adjusted
Since it was shown that medications affect the microbiome to varying degrees, this information could be incorporated into the choice of a drug in the future. If two drugs help equally well, but one affects the microbiome less, it could be preferred.
Understanding Differences Between Populations
Since medication habits vary from country to country, they could be a reason why microbiome profiles differ between countries—as well as between age groups, which tend to take more medications.
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Strengths and Weaknesses of the Study
Strengths:
- Large data base with over 2,000 participants
- Two measurement points for over 300 people
- Linking genetic data with health records
- Detailed recording of medications over five years
- Statistically sound evaluation with control of confounding factors
Limitations:
- Only prescription medications were considered—over-the-counter drugs, such as painkillers, were excluded
- It was assumed that prescribed medications were also taken—which is not always the case
- The participants were almost exclusively from Estonia—this limits the transferability to other populations
- The proportion of female participants was about seventy percent—this can skew the overall picture
- No analysis of other lifestyle factors such as diet, which can also affect the gut flora
Conclusion
The study from Estonia shows that many medications last longer than one might think—not in the blood, but in the gut. Even years after the last intake, changes in the microbiome can be detected that are associated with certain active ingredients.
This applies not only to antibiotics but also to medications that are not directly aimed at bacteria—such as antidepressants, tranquilizers, or blood pressure medications. For research and medicine, this is a clear indication: Anyone assessing the microbiome must consider the medication history.
Only in this way can truly reliable statements be made about the role of the microbiome in health and disease—and informed decisions about diagnostics and therapy be made.