Project Grant 20236701739058

** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** INFLAMMATORY BOWEL DISEASES (IBD) ARE AN INCREASINGLY IMPORTANT GLOBAL HEALTH PROBLEM; OVER 850,000 PEOPLE IN THE UNITED STATES ARE EFFECTED ANNUALLY, AND THE WORLDWIDE INCIDENCE OF IBD HAS INCREASED SINCE 1990. IBD ARE CHARACTERIZED BY CHRONIC INFLAMMATION AND ULCERATION OF THE COLON, ABDOMINAL PAIN, WEIGHT LOSS, BLOODY DIARRHEA, AND AN INCREASED RISK OF A NUMBER OF OTHER DISEASES, INCLUDING COLORECTAL CANCER AND TYPE 2 DIABETES. WHILE DIETARY, DRUG, AND BIOLOGICAL THERAPIES HAVE BEEN USEFUL IN THE MANAGEMENT OF IBD, THE ONLY 'CURATIVE' TREATMENT CURRENTLY AVAILABLE IS SURGICAL RESECTIONING OF THE COLON. IN ADDITION TO NOT BEING TRULY CURATIVE, SURGICAL OPTIONS HAVE SIGNIFICANT SIDE-EFFECTS, INCLUDING INCREASED RISK OF INFECTION. CHRONIC INFLAMMATION HAS BEEN SHOWN TO UNDERLIE IBD, AS WELL AS OTHER CHRONIC DISEASES, INCLUDING LIVER DISEASE AND DIABETES. AND THE ARYL HYDROCARBON RECEPTOR (AHR) IS A CRUCIAL REGULATOR IN THE GASTROINTESTINAL TRACT, PROMOTING BALANCE IN THE GUT WHILE LOWERING INFLAMMATION AND PROTECTING AGAINST NUMEROUS DISEASES.BOTANICALS CONTAIN HUNDREDS OF DIFFERENT PHYTOCHEMICALS, AND HAVE BEEN SHOWN TO HAVE BENEFICIAL HEALTH EFFECTS. AND CONSUMPTION OF THESE FOODS (FRUITS, VEGETABLES, NUTS, FUNGI, ETC.) HAS BEEN LINKED TO IMPROVED GASTROINTESTINAL HEALTH AND LOWER INFLAMMATION. A DIVERSE ARRAY OF FOODS, INCLUDING BROCCOLI, CORN, MUSHROOMS, CARROTS, BERRIES, ETC., HAVE DEMONSTRATED ACTIVITY IN ACTIVATING THE AHR IN PRELIMINARY STUDIES. HOWEVER, THE CHEMICAL AGENTS OF THESE FOODS THAT ARE RESPONSIBLE FOR THIS ACTIVITY REMAIN UNKNOWN. USING OUR INNOVATIVE CHEMICAL PROFILING AND DATA MODELING APPROACHES, WE WILL BE ABLE TO TEASE APART THE DIFFERING CHEMICAL SIGNATURES AND IDENTIFY WHICH MOLECULES ARE ABLE TO ACTIVATE THE AHR. WE WILL BE INVESTIGATING INTERACTIONS AT THE INTERFACE OF FOOD, NUTRITION, THE GUT MICROBIOME, AND THEIR DOWNSTREAM EFFECTS ON CHRONIC HUMAN DISEASE. USING BOTH CELLULAR AND MOUSE MODELS, WE WILL BE ABLE TO ASCERTAIN THEIR EFFECTS ON THE AHR AS WELL AS SUBSEQUENT EFFECTS ON THE GASTROINTESTINAL SYSTEM, INCLUDING THEIR ABILITY TO MITIGATE INFLAMMATORY BOWEL DISEASES.THIS PROJECT WILL PROVIDE A GREATER UNDERSTANDING OF THE MECHANISMS THAT UNDERLIE DIETARY PROTECTION AGAINST INFLAMMATORY GASTROINTESTINAL DISEASES. IT WILL LEAD TO A GREATER UNDERSTANDING OF THE BOTANICAL PHYTOCHEMICALS AND THEIR AHR ACTIVITY, AND THE DATA CAN BE USED TO GUIDE DIETARY RECOMMENDATIONS THAT MODULATE AHR ACTIVITY TO IMPROVE HUMAN GASTROINTESTINAL HEALTH AND COMBAT CHRONIC GI DISEASES. MOREOVER, THESE ENDEAVORS WILL ALLOW US TO PROVIDE PREDICTIVE MODELS AND TO ENHANCE THE ABILITY TO DISCRIMINATE BETWEEN SPECIES OR CULTIVARS AND EVEN PREDICT THE CULTIVAR AND BIOACTIVITY OF UNKNOWN BOTANICAL PRODUCT. THESE DATA WILL ALSO BENEFIT BOTANICAL USERS (SUPPLEMENT MANUFACTURERS AND CONSUMERS) BY PROVIDING A MORE NUANCED UNDERSTANDING OF THE RELATIONSHIP BETWEEN PHYTOCHEMISTRY AND BIOACTIVITY OF VEGETABLE CROPS AND BOTANICALS. WHILE THE P,RESENT STUDY IS FOCUSED ON A LIMITED SELECTION OF MODEL CROPS, THE INNOVATIVE APPROACHES ARE APPLICABLE TO ANY NUTRITIONAL OR MEDICINAL PLANT.