Mechanisms of gastrointestinal microflora on drug metabolism in clinical practice

Considered as an essential “metabolic organ”, intestinal microbiota plays a key role in human health and the predisposition to diseases. It is an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract. Since the 20th century, researches have showed that intestinal microbiome possesses a variety of metabolic activities that are able to modulate the fate of more than 30 approved drugs and immune checkpoint inhibitors. These drugs are transformed to bioactive, inactive, or toxic metabolites by microbial direct action or host-microbial co-metabolism. These metabolites are responsible for therapeutic effects exerted by these drugs or side effects induced by these drugs, even for death. In view of the significant effect on the drugs metabolism by the gut microbiota, it is pivotal for personalized medicine to explore additional drugs affected by gut microbiota and their involved strains for further making mechanism clear through suitable animal models. This review mainly focus on specific mechanisms involved, with reference to the current literature about drugs metabolism by related bacteria or its enzymes available.