ABSTRACT Phenolics-rich prebiotic fiber has been correlated with a number of positive health outcomes, however their bioavailability is typically low. A large portion the gut microbiota metabolize these fibers releasing a range of phenolic acids, which are believed to be principle bioactive components driving reduction in disease risk. Despite this, little evidence exists linking specific gut bacteria with the metabolites they produce and the downstream biological effects that these compounds exert. We therefore propose to assemble a cohort of individuals that will receive prebiotic supplementation, during comprehensive, longitudinal characterization of the microbiota and host changes with multiple omics assays (Aim 1). We will then integrate these multiomic data (Aim 2), generating unique biological signatures that define the role microbial metabolites from specific bacteria play in host biological activity. We will then isolate the microbial strains and metabolites associated with host biological activity, validate their function in gnotobiotic mice and synthesize the newly identified microbial molecules in vitro and demonstrate their structure, biological properties and applications (Aim 3). Through this study we expect to gain a detailed and clear understanding of the physiological changes, at the mechanistic level, that occur in the microbiome and host in response to dietary supplementation with prebiotic fiber.