HEMP SEED, ONCE VIEWED AS A BY-PRODUCT OF THE HEMP FIBER INDUSTRY, HAS GAINED INCREASED ATTENTION AND POPULARITY DUE TO ITS NUTRITIONAL VALUE AND POTENTIAL BENEFITS IN IMPROVING GUT HEALTH.OUR RECENT PRELIMINARY STUDY REVEALED THAT HEMP SEED CONSUMPTION REDUCED COLONIC INFLAMMATION AND RELIEVED TISSUE DAMAGE IN A DEXTRAN SULFATE SODIUM-INDUCED INFLAMMATORY BOWEL DISEASE (IBD) MOUSE MODEL, INDICATING THE POTENTIAL ANTI-COLITIS PROPERTIES OF HEMP SEED. DESPITE THESE PROMISING FINDINGS, CRITICAL GAPS REMAIN. SPECIFICALLY, IT IS UNKNOWN WHETHER HEMP SEED CAN ALLEVIATE THE CHRONIC AND SPONTANEOUS PROGRESSION OF IBD, WHICH MORE CLOSELY REFLECTS THE HUMAN DISEASE COURSE. MOREOVER, THE EXTENT TO WHICH THE GUT MICROBIOTA CONTRIBUTES TO THE EFFECT OF HEMP SEED ON COLITIS REMAINS UNCLEAR.THIS APPLICATION AIMS TO DEFINE THE EFFECT AND MECHANISM BY WHICH HEMP SEED INFLUENCES COLITIS IN THE CHRONIC SPONTANEOUS IBD MOUSE MODEL. BASED ON OUR PRELIMINARY FINDINGS, WE HYPOTHESIZE THAT DIETARY CONSUMPTION OF HEMP SEED FAVORABLY ALTERS GUT MICROBIOTA AND ALLEVIATES COLITIS IN THE SPONTANEOUS IBD MOUSE MODEL. TO TEST OUR HYPOTHESIS, WE PROPOSE TWO SPECIFIC OBJECTIVES: 1) DETERMINE THE EFFECT OF HEMP SEED ON COLITIS-ASSOCIATED INFLAMMATORY RESPONSES AND BACTERIAL DYSBIOSIS, AND 2) CHARACTERIZE THE FUNCTIONAL ROLE OF GUT MICROBIOTA IN MEDIATING THE IMPACT OF HEMP SEED ON COLITIS. THE SUCCESSFUL COMPLETION OF THIS STUDY IS EXPECTED TO SIGNIFICANTLY ADVANCE OUR UNDERSTANDING OF THE HEMP SEED-MICROBIOME-INFLAMMATION AXIS AND COULD FACILITATE THE ESTABLISHMENT OF HEMP SEED AS A NOVEL FOOD OPTION FOR IBD PREVENTION AND GUT HEALTH IMPROVEMENT. THESE OUTCOMES ARE ALSO EXPECTED TO HAVE POSITIVE IMPACTS ON U.S. AGRICULTURE BY ADVANCING THE CULTIVATION AND PRODUCTION OF HEMP SEED AND ITS DERIVED FOOD PRODUCTS (HEMPSEED MILK, OIL, COOKIES, OR CEREAL) IN THE HEALTH MARKET, AND CREATING NOVEL ECONOMIC OPPORTUNITIES FOR THE HEMP INDUSTRY IN THE U.S.TOGETHER, THIS PROPOSAL ADDRESSES THE FOOD AND HUMAN HEALTH (A1343) PROGRAM AREA PRIORITY BY INVESTIGATING HOW HEMP SEED INFLUENCES GUT MICROBIOTA AND IBD, WITH THE LONG-TERM GOAL OF IDENTIFYING SUSTAINABLE FOOD SOURCES TO PREVENT IBD AND IMPROVE GUT HEALTH.