THERE IS GROWING EVIDENCE THAT WHOLE GRAIN (WG) INTAKE PLAYS AN IMPORTANT ROLE IN CHRONIC DISEASE PREVENTION. HOWEVER, NUMEROUS HUMAN STUDIES HAVE FAILED TO SUPPORT CLEAR-CUT CONCLUSIONS ON THE TOPIC, DUE TO INDIVIDUAL METABOLIC VARIATION AND A LACK OF ACCURATE TOOLS TO ASSESS DIETARY INTAKE AND INTERNAL DOSAGE. TO BETTER UNDERSTAND THE EFFECTS OF DIET ON HEALTH MAINTENANCE AND ON THE RISK OF CHRONIC DISEASE, BIOMARKERS FOR THEIR EXPOSURE AND EFFECTS ARE NEEDED. THE MOLECULAR SIGNATURES OF WG INTAKE REMAIN UNDEFINED. THE MAJOR DIETARY CEREALS - WHEAT, RYE, AND OAT - CONTAIN DIFFERENT UNIQUE PHYTOCHEMICALS. 5-N-ALKYLRESORCINOLS (ARS) ARE PRESENT IN HIGH AMOUNTS IN WG WHEAT AND RYE, BUT ARE ABSENT FROM WG OATS. ARS AND THEIR METABOLITES HAVE BEEN REPORTED AS EXPOSURE BIOMARKERS FOR THE INTAKE OF WG WHEAT AND RYE. IN CONTRAST, AVENANTHRAMIDES (AVAS) AND OAT SAPONINS (AVENACOSIDES A AND B) ARE PHYTOCHEMICALS UNIQUE TO WG OATS. OUR HYPOTHESIS IS BIOACTIVE WG PHYTOCHEMICALS, AND THEIR METABOLITES, CAN SERVE AS THE BIOMARKERS OF WG INTAKE, REFLECT INTER-INDIVIDUAL DIFFERENCES, AND AFFECT ENDOGENOUS METABOLOME. WE RECENTLY FOUND THAT THE COMBINATION OF TARGETED AND NON-TARGETED METABOLOMICS APPROACHES CAN EFFECTIVELY IDENTIFY BIOMARKERS OF WG WHEAT INTAKE. TO TEST OUR HYPOTHESIS, WE WILL USE A TARGETED METABOLOMICS APPROACH TO IDENTIFY THE EXPOSURE BIOMARKERS OF WG WHEAT AND OAT AFTER AN ACUTE INTAKE IN A PHARMACOKINETIC STUDY IN AIM 1. IN AIM 2, WE WILL CONDUCT A CHRONIC DOSE-RESPONSE HUMAN FEEDING STUDY TO VALIDATE THE EXPOSURE BIOMARKERS IDENTIFIED IN AIM 1, IDENTIFY THE CHANGES OF THE ENDOGENOUS METABOLITES USING NON-TARGETED METABOLOMICS APPROACHES, DETERMINE WHETHER OBESITY, AGE, AND GENDER ARE MODERATORS THAT AFFECT THE METABOLIC RESPONSE TO WG, AND INVESTIGATE THE IMPACT OF GUT MICROBIOTA ON THE METABOLISM OF WG PHYTOCHEMICALS. AT THE COMPLETION OF THESE STUDIES, OUR EXPECTATION IS THAT WE WILL HAVE IDENTIFIED WG PHYTOCHEMICALS AND THEIR METABOLITES AS THE EXPOSURE MARKERS TO REFLECT WG WHEAT OR OAT INTAKE, AND THE ENDOGENOUS METABOLITES AS THE BIOMARKERS OF WG WHEAT OR OAT INTAKE FOR THEIR BENEFICIAL HEALTH EFFECTS. OUR FINDINGS WILL ESTABLISH THE BASIS FOR FUTURE MECHANISTIC STUDIES OF THE ROLE OF WGS IN HEALTH, AND PROVIDE NOVEL INSIGHT INTO RELIABLE SPECIFIC BIOLOGICAL INDICATORS FOR WG INTAKE AND EVENTUALLY LEAD TO FUTURE INDIVIDUALIZED NUTRITION. THIS KNOWLEDGE COULD BE UTILIZED TO IMPROVE HOW TO ASSESS THE IMPACT OF WG ON HEALTH.