Numerous studies with varying degrees of statistical power have found correlations between the composition of the bacterial population in the human gut microbiome and disease states. But the molecules and mechanism(s) connecting a dysbiotic microbiome to a specific disease are generally unknown. In an attempt to address this gap, we undertook a series of screens to link bacterial metabolites with diseases like type 1 diabetes (T1D) and inflammatory bowel disease (IBD). We focused on primary drivers of inflammation like TNFα (tumor necrosis factor alpha) produced by human dendritic cells. This seminar will describe our screening logic, the selection of candidate bacterial strains, the discovery of the small molecule regulators of cytokine production, their structures and biosynthesis, and inflammatory mechanism.
