Medications can influence the community of microbes living in the human gut long after a person stops taking them, according to a large study led by researchers at the University of Tartu Institute of Genomics.
The findings suggest that a person’s prescription history may help explain differences in the gut microbiome years later. The gut microbiome includes the vast community of bacteria and other microorganisms that live in the digestive tract and can influence digestion, metabolism, immune function, and other aspects of health.
Drug Effects May Persist for Years
Researchers analyzed stool samples and prescription records from more than 2,500 participants in the Estonian Biobank who were part of the Estonian Microbiome cohort. They found that most of the medications examined were associated with differences in the gut microbiome.
For a substantial number of drugs, those differences could still be detected years after people had stopped taking the medication.
The lasting effects were not limited to antibiotics, which are already well known for their ability to disrupt populations of gut bacteria. Antidepressants, beta-blockers, proton pump inhibitors, and benzodiazepines were also associated with distinctive microbial “fingerprints.”
Beta-blockers are commonly used to treat conditions such as high blood pressure and certain heart problems. Proton pump inhibitors reduce stomach acid and are often prescribed for acid reflux and related conditions. Benzodiazepines are medications commonly used for anxiety and other disorders.
“Most microbiome studies only consider current medications, but our results show that 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.
The finding suggests that researchers studying connections between the microbiome and disease may need to look beyond the medications a person is currently taking. Drugs used months or even years earlier could still influence the microbial patterns seen in a stool sample.
Anxiety Drugs Show Surprisingly Strong Effects
One particularly striking finding involved benzodiazepines, which are commonly prescribed for anxiety. Their associations with the gut microbiome were comparable to those seen with broad-spectrum antibiotics.
Broad-spectrum antibiotics are designed to act against many different types of bacteria, which is why they can produce substantial changes in the gut microbial community.
The study also found that medications belonging to the same drug class did not necessarily affect the microbiome in the same way. Drugs that may be prescribed for similar conditions, such as diazepam and alprazolam, differed in how strongly they appeared to disrupt gut microbes.
That distinction could be important because medications are often grouped together in microbiome research based on their drug class. The new results suggest that individual drugs may need to be considered separately.
Follow-Up Samples Reveal Predictable Changes
Researchers also examined follow-up stool samples from a smaller group of participants. These samples allowed them to observe what happened when people started or stopped certain medications.
Those changes were accompanied by predictable shifts in gut microbes, providing evidence that the medications themselves may be responsible for at least some of the observed differences.
Although the second time-point analysis involved a relatively small number of participants, researchers were able to confirm persistent effects linked to proton pump inhibitors, selective serotonin reuptake inhibitors and antibiotics, such as penicillins in combination and macrolides.
Selective serotonin reuptake inhibitors are a widely used class of antidepressants. Macrolides are a group of antibiotics that includes drugs used to treat a range of bacterial infections.
Medication History Could Matter in Microbiome Research
The results add to growing evidence that the gut microbiome reflects more than a person’s current diet, lifestyle, health, and medication use. Past treatments may leave biological traces that remain detectable long after the prescription has ended.
“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.”
Accounting for that history could help scientists more accurately distinguish microbiome changes associated with disease from changes caused by medications taken in the past.