Department of Systems and Computational Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States of America; Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States of America. Electronic address: [Email]
Our understanding of the scope and clinical relevance of gut microbiota metabolism of drugs is limited to relatively few biotransformations targeting a subset of therapeutics. Translating microbiome research into the clinic requires, in part, a mechanistic and predictive understanding of microbiome-drug interactions. This review provides an overview of microbiota chemistry that shapes drug efficacy and toxicity. We discuss experimental and computational approaches that attempt to bridge the gap between basic and clinical microbiome research. We highlight the current landscape of preclinical research focused on identifying microbiome-based biomarkers of patient drug response and we describe clinical trials investigating approaches to modulate the microbiome with the goal of improving drug efficacy and safety. We discuss approaches to aggregate clinical and experimental microbiome features into predictive models and review open questions and future directions toward utilizing the gut microbiome to improve drug safety and efficacy.