Antibiotics are known to kill not only harmful bacteria but also beneficial microbes in the body, weakening the microbiome’s natural defense known as colonization resistance against infections. Emerging research now shows that non-antibiotic drugs can also disrupt the gut microbiome though it has been unclear which of these disruptions are harmless and which may pose health risks. In a new study from Yale School of Medicine researchers identified several commonly prescribed non-antibiotic drugs that significantly alter the microbiome. Notably one drug caused mice to produce antimicrobial compounds that attack their own gut microbes. These findings suggest that the microbiome may play a critical role in individual drug responses and could become a valuable target for improving treatment outcomes.

When Aman Kumar PhD and Andrew Goodman PhD set out to investigate the effects of non-antibiotic drugs on the microbiome they encountered a challenge: most microbiome studies were either too small to detect drug-induced disruptions or too large and long-term to include microbiome data. Still the researchers suspected that large-scale datasets might hold indirect clues. Since individuals with disrupted microbiomes face a higher risk of gastrointestinal (GI) infections due to reduced colonization resistance they hypothesized that prescription drugs linked to increased GI infections could be the culprits. By collaborating with epidemiologists and analyzing over ten years of medical records and pharmacy claims from one million individuals in Montreal’s universal health insurance system they identified several non-antibiotic drugs that elevated infection risk some to the same extent as antibiotics.

To investigate how specific prescription drugs affect the microbiome the researchers administered each drug to mice and analyzed fecal samples collected before and after treatment. They found that nearly half of the drugs caused changes in the microbiome’s composition, and four in particular digoxin clonazepam  pantoprazole and quetiapine were linked to an increased risk of infection following exposure to pathogens. Digoxin which produced the most significant microbiome disruptions became the focus of further study. Rather than directly harming gut microbes digoxin activated a biological pathway that led mice to release antimicrobial proteins into the small intestine proteins that selectively targeted only a few microbial species. Despite affecting a small subset the loss of these key microbes had a profound impact on the gut ecosystem.

Before digoxin treatment certain gut microbes help keep the immune system in a state of readiness against pathogens. However digoxin-induced antimicrobial proteins eliminate these key microbes weakening this defense. This loss creates an environment where harmful pathogens like Salmonella can thrive and cause infection. Notably similar effects were observed even in mice colonized with human microbiomes.

While millions in the U.S. rely on prescription drugs these findings don’t suggest patients should stop taking them but they do highlight the need for deeper investigation into their impact on the microbiome. Kumar aims to apply similar methods to study links between medications and diseases like IBD and colon cancer. This research offers a new framework for examining drug-induced microbiome disruptions. Understanding these connections could help identify at-risk individuals and lead to targeted therapies.

Source: https://medicine.yale.edu/news-article/non-antibiotic-drugs-also-disrupt-the-microbiome/