Abstract: Human-associated bacteria play a vital role in human health, and microbial imbalance has been linked to a wide range of disease states. However, the ways in which bacteria affect the host at a molecular level remain poorly understood. In order to harness connections between the microbiome and disease to improve human health, we need to know more about the molecules and chemical mechanisms driving host-microbiota interactions. The goal of our research is to understand and control the chemistry of human-associated bacteria in order to uncover how the microbiome affects human health and disease. Our current work is focused on how human gut bacteria metabolize host-produced small molecules and how the resultant compounds affect host physiology, and in particular, host metabolism, immune function, and neurological function and behavior. Host-produced compounds such as bile acids, steroids, and vitamins act as crucial signaling molecules and regulators of host biology, but their metabolism by gut bacteria has been relatively unexplored. Here I will discuss our recent progress toward uncovering the biosynthetic pathways and biological roles of host-produced, bacterially modified metabolites.