We study the large pool of chemicals produced by gastrointestinal bacteria with the goal of understanding how these molecules impact human health. Our approach uses classical techniques in bacterial genetics coupled with high dimensional mass spectrometry to uncover metabolic pathways in the gut microbial ecosystem. We then develop model systems in gnotobiotic mice where the metabolic output of gut bacteria is genetically controlled. This system allows us to interrogate host-microbe interactions experimentally and reveal new mechanisms by which small molecules from the gut microbiota alter host physiology. We then use this knowledge to test predictions of how the presence of these microbially derived small molecules impact human health. In tandem, we are developing new diagnostic strategies to study gut microbiome metabolic activity in humans which represents an important approach for establishing concrete connections between microbiome activity and human health.