Humans are colonized by vast numbers of symbiotic microorganisms whose metabolisms are inextricably intertwined with our own. To understand how chemical transformations performed by the human microbiota influence human health, and to intervene therapeutically in diseases, it is critical that we link these metabolic functions to specific genes and organisms. My research group seeks to discover and understand the molecular basis of disease-associated metabolic pathways from the human gut microbiota. We use an understanding of chemical structure-reactivity principles and biosynthetic logic to devise hypotheses that associate bacterial genes with metabolic functions. We are also developing both bioinformatic and experimental approaches for characterizing and manipulating these activities in complex microbial communities. Ultimately, we aim to access chemical tools that interface with human gut bacteria and could serve as initial leads for the development of microbiota-targeted small molecule drugs. In this talk I will discuss our ongoing efforts to identify the genes and chemical mechanisms underlying multiple disease-associated microbial activities. I will also describe potential approaches for modulating microbial metabolism in the gut and how such strategies relate to other therapeutic opportunities and challenges presented by the human microbiota.