Maier et al., 2018. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature.

This is a summary of our DalMUG journal club discussion of the above paper written by Casey Jones.

Summary

In drug development, studies on mechanism of action and off-target effects are a must for health agency approval, but the impact of these drugs on the gut microbiome are largely ignored. Some associations between the microbiome and drugs have been found with compounds such as metformin and NSAIDs, but here Maier et al. sought out to systematically profile interactions between common drugs and individual gut bacteria.

They analyzed the growth of 40 representative isolates of the gut microbiome under a high-throughput growth inhibition screen with 1,197 compounds. This “ubiquitous” set of 40 microbes that were used in the experiments is representative of 78% assignable relative abundance of bacterial genera from four diverse populations, including HMP data. This set was chosen to be representative of mostly commensal bacteria found in the guts of healthy humans.

We were pleased with the design of the study and its findings. One of the most notable results was that 203 (24%) of human-targeted drugs were active against bacterial growth in the screen. Forty of these drugs affected at least 10 strains of bacteria. These included drugs known to affect microbiota such as methotrexate, tamoxifen, and 5-fluorouracil but 14 of the 203 human-targeted drugs had no previously known antibacterial activity.

This robust analysis of how common drugs affect common gut microbes is beneficial information for drug makers and clinicians. When treating patients with gastrointestinal issues, a list of drugs that affect the microbiome may one day inform prescription choices by clinicians.

Points of Interest

• 24% of the human-targeted drugs tested had inhibitory effects on gut commensals.
• Gammaproteobacteria representatives were the most resistant to drug treatment of the taxa studied.
• Typical features of drugs that had anti-commensal activity included antineoplastics, hormones, and nervous system targeting drugs.
• Antipsychotics were enriched in hits that inhibited gut bacteria. The authors raise the possibility that the mechanism of action of antipsychotics may be related to their direct bacterial inhibition, adding to evidence for the gut-brain axis.

Points of Consideration

• Testing the same drugs on the inhibition of pathogenic bacteria would have been a nice addition.
• Testing of the same drugs on mixed communities of bacteria, either in-vitro or in-vivo, may result in differences in inhibition.