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 Institute of Genomics at the University of Tartu.
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.
The effects of drugs can persist for years
The researchers analyzed stool samples and prescription records from more than 2,500 Estonian Biobank participants 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 medications, those differences could still be detected years after people had stopped taking them.
The lasting effects were not limited to antibiotics, which are already well known for their ability to alter intestinal bacteria populations. 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 medication use may be as important as a surprisingly strong factor in explaining individual differences in the microbiome,” 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. Medications used months or even years earlier could still influence the microbial patterns seen in a stool sample.
Anti-anxiety drugs show surprisingly strong effects
One particularly surprising finding was for benzodiazepines, which are commonly prescribed for anxiety. Its 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, so they can produce substantial changes in the intestinal microbial community.
The study also found that medications belonging to the same drug class did not necessarily affect the microbiome in the same way. Medications that may be prescribed for similar conditions, such as diazepam and alprazolam, differed in how strongly they appeared to alter gut microbes.
That distinction could be important because drugs are often grouped in microbiome research according to their drug class. The new results suggest that individual medications may need to be considered separately.
Follow-up samples reveal predictable changes
The 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 changes in gut microbes, providing evidence that the drugs themselves may be responsible for at least some of the observed differences.
Although the second time analysis involved a relatively small number of participants, the researchers were able to confirm persistent effects related to proton pump inhibitors, selective serotonin reuptake inhibitors, and antibiotics such as combination penicillins and macrolides.
Selective serotonin reuptake inhibitors are a widely used class of antidepressants. Macrolides are a group of antibiotics that includes medications used to treat a variety of bacterial infections.
Medication history could be important in microbiome research
The results add to growing evidence that the gut microbiome reflects more than a person’s diet, lifestyle, health and current medication use. Previous treatments can leave biological traces that remain detectable long after the prescription ends.
“This is a comprehensive systematic evaluation of long-term drug effects on the microbiome using real-world medical records,” said Professor Elin Org, corresponding author. “We hope this encourages researchers and clinicians to take medication history into account when interpreting microbiome data.”
Taking that history into account could help scientists more accurately distinguish changes in the microbiome associated with diseases from changes caused by medications taken in the past.