THE GUT MICROBIOTA AND MICROBIAL METABOLITES HAVE SUBSTANTIAL IMPACT ON HEALTH AND DISEASE IN LOCAL GUT AS WELL AS REMOTE ORGANS SUCH AS THE BRAIN VIA COMPLICATED GUT-BRAIN AXIS. FOOD IS A STRONG MODULATOR OF THE GUT MICROBIOME. THE WALNUT IS A WELL-KNOWN FOOD SUPPLEMENT THAT IMPROVES METABOLIC FUNCTION, REDUCES COLON CANCER RISK AND LOWERS DEPRESSION SCORE. SEVERAL STUDIES--INCLUDING OURS--HAVE DEMONSTRATED THAT WALNUT CONSUMPTION RECONFIGURED THE MICROBIOME TOWARDS AN ANTI-INFLAMMATORY MILIEU, RAISING THE POSSIBILITY THAT THE MICROBIOME MAY MEDIATE WALNUT-ASSOCIATED HEALTH BENEFITS. OUR UNDERSTANDING OF THE RELATIONSHIP BETWEEN WALNUTS, MICROBIOME AND OVERALL HUMAN HEALTH, INCLUDING OF DISTANT ORGAN SYSTEMS IS INCOMPLETE. BY LEVERAGING STATE-OF-ART WHOLE GENOME SHOTGUN SEQUENCING AND METABOLOME ASSAY, OUR PROPOSED STUDY WILL COMPREHENSIVELY CHARACTERIZE THE FULL MICROBIOME (BACTERIAL SPECIES, VIRUSES, FUNGI) CHANGES IN RESPONSE TO WALNUT CONSUMPTION; DELINEATE THE RELATIONSHIP BETWEEN INTERVENTION DURATION AND PERSISTENCE OF THE MICROBIOME CHANGES; SIMULTANEOUSLY MAP AND TRACK THE SPATIAL AND TEMPORAL DYNAMICS OF METABOLOME FROM FECAL PELLETS TO GUT MUCOSA TISSUE, CIRCULATION AND THE BRAIN; AND MOST IMPORTANTLY, DETERMINE WHETHER THE MICROBIOME PLAYS AN CAUSAL ROLE IN WALNUT-ASSOCIATED METABOLIC BENEFITS.