THERE IS INCREASING EVIDENCE THAT DIET AND THE GUT MICROBIOTA HAVE SIGNIFICANT IMPACT ON AN INDIVIDUAL'S COLORECTAL CANCER RISK. CRUCIFEROUS VEGETABLES HAVE ANTI-TUMOR ACTIVITIES, AND THE MICROBIOTA CAN CONTRIBUTE TO THE GENERATION OF BIOACTIVE METABOLITES. AS DIET CAN ALSO AFFECT THE COMPOSITION OF THE GUT MICROBIOTA, IT IS POSSIBLE THAT EXPOSURE TO CRUCIFEROUS VEGETABLES MAY INDUCE CHANGES IN THE GUT MICROBIOTA THAT PROMOTE INTESTINAL HOMEOSTASIS. OUR LONG-TERM GOAL IS TO UNDERSTAND THE INTERRELATIONSHIP BETWEEN THE GUT MICROBIOTA AND THE TUMOR SUPPRESSIVE ACTIVITIES OF BROCCOLI SPROUTS. WE PROPOSE THREE OBJECTIVES. FOR OBJECTIVE 1, WE WILL EXAMINE THE EFFECTS OF DIFFERENT BROCCOLI SPROUT DIETS AND THEIR MAJOR METABOLITES ON COLON TUMORIGENESIS BY USING TWO DIFFERENT MOUSE MODELS. OBJECTIVE 2 WILL HELP DETERMINE THE ROLE OF THE GUT MICROBIOTA ON THE METABOLISM OF DIETARY GLUCOSINOLATES (GSLS) DERIVED FROM CRUCIFEROUS VEGETABLES. WE WILL EVALUATE THE EFFECTS OF GSL-RICH DIETS ON THE COMPOSITION OF THE GUT MICROBIOME, AND THE EFFECT OF THE MICROBIOTA ON THE METABOLISM OF GSLS. FINALLY, OBJECTIVE 3 WILL DETERMINE WHETHER THE PROTECTIVE EFFECT OF BROCCOLI SPROUTS IS MEDIATED BY THE GUT MICROBIOTA THROUGH THE USE OF GERMFREE MICE AND MICROBIOME TRANSFER EXPERIMENTS. THIS PROJECT DIRECTLY ADDRESSES THE FUNCTION AND EFFICACY OF NUTRIENTS IN BROCCOLI SPROUTS IN REDUCING SUSCEPTIBILITY TO COLON TUMORIGENESIS AND WILL LAY THE GROUNDWORK FOR THE DEVELOPMENT OF STRATEGIES THAT INVOLVE MODULATION OF THE DIET AND MICROBIOTA FOR COLON CANCER PREVENTION.