Gut Microbiota in Drug Metabolism: A New Frontier in Precision Medicine

Abstract: The gut microbiota, an intricate network of trillions of microbes, is responsible for drug metabolism and affects pharmacokinetics, efficacy, and toxicity. Recent findings in pharmacology and microbiome research emphasize the importance of gut microbes in modulating drug absorption, biotransformation, and excretion, making them a key driver of interindividual variability in drug response. Microbial enzymes activate, inactivate, or modify drug structures and affect therapeutic responses. Dysbiosis, a disruption of gut microbial composition, has been implicated in disrupted drug metabolism leading to adverse drug reactions and failure of therapy. As precision medicine takes centre stage, knowledge of the role of gut microbiota in drug metabolism opens the door for microbiome-based therapies, including probiotics, prebiotics, and faecal microbiota transplantation, to tailor drug therapy. Pharmacometagenomics is a new field that seeks to incorporate microbiome profiling into customized drug regimens, minimizing drug response variability and enhancing patient outcome. This review delves into the complex relationship between gut microbiota and drug metabolism, addresses important microbial enzymes for drug biotransformation, and identifies potential strategies to capitalize on microbiome data for precision pharmacotherapy. Through connecting microbiology with pharmacology, research into the gut microbiota provides new understandings into tailored treatment strategies and influencing the course of drug discovery and clinical applications. Keywords: Gut microbiota, Drug metabolism, Pharmacokinetics, Precision medicine, Pharmacometagenomics, Microbial enzymes Microbiome-based therapies