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There are many factors that impact the composition and health of the gut microbiome: genetics, age, environment, diet, and medications are a few critically important ones. Antibiotics are known to be particularly disruptive to the microbial ecosystem, destroying both pathological and beneficial organisms. Yet, research has shown that commonly prescribed non-antibiotic drugs for a variety of medical conditions also have unique impacts on the microbiome.

Researchers from the Netherlands investigated this drug-microbe relationship through a meta-analysis of three independent groups of participants: a general population cohort, an inflammatory bowel disease (IBD) cohort, and irritable bowel syndrome (IBS) cohort. Together, IBD and IBS cohorts were termed the “disease cohorts,” which had lower microbial diversity than the general population. Including IBD and IBS groups, allowed evaluation of how baseline differences of gut microbiota in disease states – and increased polypharmacy of these cohorts – impacts microbial response and function. The total number of participants in all 3 cohorts was n=1883.

“…proton pump inhibitors (“PPIs”- used for acid suppression/heartburn), metformin (used for diabetes), vitamin D supplements, and laxatives had the highest number of microbiome associations.”

Metagenomics sequencing was performed on stool samples from all groups. After controlling for demographic and physical attributes (age, sex, race, BMI), 19 of 41 medication categories were associated with microbial features. In the single drug analyses, proton pump inhibitors (“PPIs”- used for acid suppression/heartburn), metformin (used for diabetes), vitamin D supplements, and laxatives had the highest number of microbiome associations. Changes in abundance of microbial strains were associated with multiple drugs classes. For example, users of opiates, oral steroids, anti-platelet medications, PPIs, selective serotonin re-uptake inhibitors (“SSRIs” – a class of antidepressants), and vitamin D supplements, had increased abundance of Streptococcus salivarius – which generally colonizes the mouth and upper respiratory track.

Other changes were specific to individual drug classes and consistent with previous observations in smaller samples: for example, PPI users had increased Bifidobacterium dentium, whereas antibiotic users had decreased Bifidobacterium. Alistipes – which may play a role in the pathogenesis of constipation- and Bacteroides species were increased in laxative users, and Eubacterium ramulus was increased in SSRI users.

“Use of different drugs was also associated with changes in gut function by varying the activity of certain microbial pathways.”

When correcting for use of multiple medications at the same time, multi-drug analyses showed that PPIs, laxatives, antibiotics, and metformin had the greatest number of associations with microbiome pathways. The first three of those drug classes had the largest effect on microbiome composition. Users of 15 different drugs across all three cohorts had increased total antibiotic resistant genes compared to non-users of these drugs.

Only the PPI class consistently altered the gut ecosystem across all cohorts, which is potentially explained by their mechanism of action of decreasing stomach acidity which allows growth and survival of upper intestinal bacteria in the lower gut. Concurrent use of multiple drugs also impacted the gut composition, but there were no observed significant changes in microbial richness, the numbers of species.

“…the resulting changes may impact their response to diet, stress, and additional drugs.”

Given our developing understanding of the gut-brain-immune system the above work may have clinical implications, as a person’s daily medications significantly influence their microbial ecosystem. Even though not tested in this study, the resulting changes may impact their response to diet, stress, and additional drugs. As gut microbes also have been shown to play an important role in drug metabolism, it is conceivable that the effects of commonly used drugs such as PPIs, the antidiabetic drug metformin and laxatives on the gut microbes affect the metabolism of other drugs.

In the future, listed side effects of drugs will probably have a list of their effects on your gut microbiome, and will warn you of possible undesired consequences.