THROUGHOUT THE DAY WE EXPOSE OUR INTESTINAL CELLS, WHICH CONTAIN MANY IMMUNE-CELLS, TO DIET-DERIVED FOREIGN MATERIALS. THE CONSTANT STIMULI OF SUCH MOLECULES HAVE SHAPED OUR IMMUNE-SYSTEM IN THE EVOLUTIONARY PROCESS. HOWEVER, WITH THE ONSET OF THE INDUSTRIAL REVOLUTION, THE HUMAN WESTERN DIET HAS CHANGED DRAMATICALLY. OUR FOODS HAVE BECOME PROCESSED TO PROLONG SHELF LIFE, AND THE USE OF CHEMICAL ADDITIVES TO CONTROL FLAVOR IS NOT UNCOMMON. CLEARLY, THE INTAKE OF VEGETABLES HAS DRAMATICALLY REDUCED TOO. THE DIETARY CHANGES OCCURRED SUDDENLY ON AN EVOLUTIONARY TIME-SCALE LEAVING LIMITED OPPORTUNITY FOR ADAPTATION OF OUR IMMUNE-SYSTEM. INDEED, THE WESTERN DIET IS A MAJOR CONTRIBUTING FACTOR TO (CHRONIC) INTESTINAL INFLAMMATION. CHRONIC INTESTINAL INFLAMMATION CAN LEAD TO DEBILITATING DISEASES SUCH AS COLITIS AND CROHN'S DISEASE, WHICH ARE COLLECTIVELY CALLED INFLAMMATORY BOWEL SYNDROME (IBD). A SERIOUS LONG-TERM COMPLICATION ASSOCIATED WITH IBD IS THE DEVELOPMENT OF A MULTITUDE OF CANCERS. THUS, IBD IS A PRESSING ECONOMIC BURDEN ON SOCIETY WHICH, IN THE US ALONE, IS PREDICTED TO EXCEED ANNUALLY $10 BILLION AND AFFECTS MORE THAN 3 MILLION AMERICANS.THIS PROJECT SEEKS TO DETERMINE 1) TO WHAT EXTEND DO VEGETABLE-DERIVED MOLECULES REDUCE INTESTINAL INFLAMMATION AND 2) WHAT ELEMENTS OF THE IMMUNE-PATHWAY IN THE HOST ARE RESPONSIBLE FOR SUPPRESSION OF INTESTINAL INFLAMMATION. WE WILL STUDY THE INFLUENCE OF TWO VEGETABLE-DERIVED MOLECULES: 1) ORGANOSULFUR COMPOUNDS (OSC), ASSOCIATED WITH E.G. GARLIC AND ONIONS; 2) INDOLE-DERIVATIVES (IDS), ASSOCIATED WITH E.G. BROCCOLI AND CAULIFLOWER. WE WILL CHEMICALLY-INDUCE INTESTINAL INFLAMMATION IN MICE, WHICH IS CHARACTERIZED BY TISSUE INFLAMMATION AND DESTRUCTION OF THE INTESTINAL LINING. THE LATTER OUTCOME LEADS TO LEAKING OF INTESTINAL CONTENTS TO THE BLOODSTREAM WHICH INCREASES SYSTEMIC INFLAMMATION. WE WILL TREAT ANIMALS WITH OSC, IDS, OR A COMBINATION OF BOTH. PREVENTION OR REDUCTION OF INTESTINAL INFLAMMATION WILL BE DETERMINED BY ASSESSING THE INTEGRITY OF THE INTESTINE AND THE INFLAMMATORY IMMUNE-PROFILE. COLLECTIVELY, IT IS EXPECTED THAT THESE EXPERIMENTS WILL SHOW 1) THE RELATIVE PREVENTIVE EFFECTS OF OSC AND IDS INDIVIDUALLY AGAINST INTESTINAL INFLAMMATION, AND 2) IF THERE IS ANY COOPERATIVITY BETWEEN THESE DIETARY AGENTS. PROTECTIVE EFFECTS ARE EXPECTED TO ULTIMATELY LEAD TO HUMAN CLINICAL TRIALS TO USE RATIONAL APPROACHES TO MAP OUT THE DIETARY GUIDELINES THAT CAN HELP MANAGE OR AMELIORATE IBD. IF WE OBSERVE A CUMULATIVE AND/OR A COOPERATIVE EFFECT OF OSC AND IDS, THIS WOULD INDICATE THAT PERHAPS ONLY MODEST CHANGES IN THE INTAKE OF E.G. BROCCOLI AND ONION IS NEEDED TO OBTAIN TANGIBLE PROTECTIVE EFFECTS. SUCH RESULTS WOULD PROVIDE STRONG INCENTIVE TO PROMOTE THE INTAKE OF SELECT VEGETABLES IN SOCIETY.