Drug metabolism as a lens on gut microbial ecology and microbiota-host interactions

The human gut microbiome varies between individuals, creating diverse metabolic ecosystems that interact with host physiology. Yet the principles governing these metabolic microbiota-host interactions remain poorly understood. We use therapeutic drugs as chemically diverse, exogenous probes to dissect microbial metabolic functions under controlled conditions. Combining high-throughput microbial cultivation, genetic screening, metabolomics, genomics, and gnotobiotic mouse models, we connect variation in microbial community composition with emergent metabolic activities and host phenotypes. These bottom-up approaches reveal how species, genes, and community structures shape metabolic exchange between microorganisms and their host and provide mechanistic insights into microbial community functions.