Dissecting the human gut microbiome to better decipher drug liability: A once-forgotten organ takes center stage

We present comprehensive mechanisms and co-contributing factors by which the gut microbiome influences drug therapeutic outcomes. We highlight in vitro, in vivo, and in silico models for elucidating the mechanistic role and clinical impact of the gut microbiome on drugs in combination with high-throughput, functionally oriented, and physiologically relevant techniques. Integrating pharmaceutical knowledge and insight, we provide practical suggestions to pharmaceutical scientists for when, why, how, and what is next in microbial studies for improved drug efficacy and safety, and ultimately, support precision medicine formulation for personalized and efficacious therapies.