Microbiota and non-antibiotic drugs interactions: friends or foes?

Previous studies showed that metformin, proton pump inhibitors, NSAIDs, and atypical antipsychotics have an effect on the intestinal microbiota composition. However, these studies presented general results for drug classes instead of specific drugs. Lisa Maier and colleagues published their new study results in Nature in 2018, and they aimed to generate a comprehensive resource of more than 1,000 drugs actions on the microbiome (against 40 representative gut bacterial strains), which could facilitate more in-depth clinical and mechanistic studies, ultimately improving therapy and drug design. Maier et al. [1] showed that 24% out of these 1,000 drugs inhibited the growth of at least one strain in vitro. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans, like previously published human studies. This study showed that susceptibility to antibiotics and human- targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, and highlighted the potential risk of non-antibiotics promoting antibiotic resistance. Widespread worldwide use of pharmaceutical drugs might be related with the dysbiosis, especially in modern Western societies.

This recent trial also showed that the intestinal microbiota composition can also modulate drug efficacy and toxicity and might be a new platform for further drug development; however, further in vivo clinical trials are necessary to better understand the mechanism of action. A comprehensive understanding of how therapeutics interact with gut microbes will open up the path for further mechanistic dissection of such interactions, and ultimately improve not only our understanding of the gut microbiome, but also drug safety and efficacy [2].