** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS PROJECTRESPONDS TO USDA-NIFA AFRI FOUNDATION PROGRAM FOR FOOD SAFETY, NUTRITION AND HEALTH IN THE PROGRAM AREA OF FOOD AND HUMAN HEALTH (A1343). WE WILL EXAMINE INTERACTIONS BETWEEN BRASSICA, GUT MICROBIOME (GM) AND GLP-1 SECRETION. BRASSICA VEGETABLES ARE A RICH SOURCE OF GLUCOSINOLATES (GSLS), A GROUP OF SULFUR COMPOUNDS THAT ARE UNIQUE TO THESE VEGETABLES (BROCCOLI, KALE, AND OTHERS). UPON HYDROLYSIS, GSLS ARE CONVERTED TO BIOACTIVE ISOTHIOCYANATES (ITCS). WHEN CONSUMED RAW, GSLS CAN BE CONVERTED TO ITCS BY THE PLANT ENZYME MYROSINASE. HEAT (COOKING) INACTIVATES MYROSINASE, THEN GUT MICROBIOTA (GM) BECOME RESPONSIBLE FOR ANY GSL CONVERSION TO ITCS. WE HYPOTHESIZE THAT NON-ITC PRODUCING PATHWAYS PRESENT IN THE GM ARE COMPETING FOR GSLS AND THUS EXPLAIN THE DRAMATIC INTER-INDIVIDUAL DIFFERENCES SEEN IN ITC PRODUCTION (AIM 1). ONCE THOUGHT TO BE ONLY PRESENT IN THE MOUTH, BITTER-TASTE RECEPTORS (T2RS) ARE NOW FOUND TO BE PRESENT IN MANY TISSUES INCLUDING THE GUT. SINCE GUT T2RS CAN TRIGGER GLP-1 SECRETION AND ITCS CAN SERVE AS T2R AGONISTS, WE HYPOTHESIZE THAT ITCS PRODUCED BY THE GM BIND INTESTINAL T2R(S) TO TRIGGER GLP-1-DEPENDENT CONTROL OF OBESITY AND GLUCOSE HOMEOSTASIS (AIM 2). OPTIMIZING ITC PRODUCTION IN THE GUT, BOTH AMOUNT AND LOCATION, HAS THE POTENTIAL TO REVERSE GLUCOSE INTOLERANCE AND OBESITY IN HUMANS. OUR FINDINGS WILL INFORM THE PUBLIC ABOUT THE HEALTH PROMOTING PROPERTIES OF BRASSICA, EXPLAIN THE VARIATION IN GSL BIOACTIVATION SEEN IN HUMAN STUDIES, WHERE NON-ITC METABOLISM OF GSLS BY GM HAVE BEEN LITTLE CONSIDERED, AND WILL FURTHER INCREASE BRASSICA INTAKE WORLDWIDE.