Identification and Characterization of Microbial Metabolites in Immunity

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PROJECT SUMMARY The human microbiome is a key regulator of host immune function, and growing consensus suggests this relationship is likely mediated by host interactions with microbial derived small molecules (i.e., metabolites). Accordingly, microbial derived metabolites have been associated with numerous autoimmune, allergic, and infectious diseases. However, the host-microbiome circuits that form the molecular basis of these associations have not been fully characterized, and many microbial derived metabolites have not even been formally identified. In this proposal, we describe a strategy to identify and functionally characterize microbial derived metabolites isolated from patients in health and autoimmunity. Our collaborative team will isolate and characterize novel metabolites from the human microbiome, map these associations to human immune pathways, and identify the specific host receptors that engage microbial derived metabolites. This proposal will establish causal relationships between microbial metabolites and human immune system function.