** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** 1. CURRENT ISSUE OR PROBLEM AND ITS IMPORTANCETHE RESEARCH ADDRESSES THE HEALTH IMPLICATIONS OF CONSUMING FOODS PREPARED IN THERMALLY ABUSED OILS (TAOS), WHICH ARE PREVALENT IN THE FAST-FOOD INDUSTRY. THESE OILS, WHEN REPEATEDLY HEATED, DEGRADE AND GENERATE HARMFUL LIPID OXIDATION PRODUCTS (LOPS). CONSUMING FOODS FRIED IN THESE OILS IS LINKED TO INCREASED RISKS OF CHRONIC DISEASES, INCLUDING GUT HEALTH DISORDERS AND COLORECTAL CANCER. THIS RESEARCH IS ESSENTIAL BECAUSE A SIGNIFICANT PORTION OF THE POPULATION CONSUMES FAST FOOD REGULARLY, AND UNDERSTANDING THE HEALTH IMPACTS OF TAOS CAN LEAD TO IMPROVED DIETARY GUIDELINES AND HEALTHIER COMMERCIAL FOOD PREPARATION METHODS. BEYOND INDIVIDUAL HEALTH, THIS RESEARCH HAS BROADER IMPLICATIONS: ECONOMICALLY, BY POTENTIALLY REDUCING HEALTHCARE COSTS AND IMPROVING PRODUCTIVITY; COMMUNITY-WISE, BY ENHANCING PUBLIC HEALTH; ENVIRONMENTALLY, BY PROMOTING MORE SUSTAINABLE COOKING PRACTICES; AND IN AGRICULTURE, BY INFLUENCING THE PRODUCTION OF HEALTHIER COOKING OILS.2. METHODS AND APPROACHESIN OUR STUDY, WE WILL EXPLORE THE EFFECTS OF THERMALLY OXIDIZED OILS (TAOS) ACROSS THREE KEY OBJECTIVES USING C57BL/6J MICE TO MIMIC HUMAN DIETARY PATTERNS. THE FIRST OBJECTIVE INVESTIGATES HOW DIFFERENT DURATIONS OF TAO EXPOSURE--ACUTE, SUBCHRONIC, AND CHRONIC--AFFECT GUT INFLAMMATION, MICROBIOME COMPOSITION, AND IMMUNE RESPONSES. MICE WILL BE FED DIETS WITH VARYING LEVELS OF OXIDIZED OILS AND WILL UNDERGO THOROUGH HEALTH MONITORING, INCLUDING ANALYSIS OF COLON TISSUE AND BLOOD FOR VARIOUS BIOMARKERS, ALONG WITH REGULAR FECAL SAMPLING TO OBSERVE MICROBIOME CHANGES OVER TIME. THE SECOND OBJECTIVE ASSESSES THE IMPACT OF CHRONIC TAO EXPOSURE ON COLITIS AND COLON CANCER DEVELOPMENT USING A MOUSE MODEL OF COLITIS-ASSOCIATED COLORECTAL CANCER TO SIMULATE HUMAN DISEASE PROGRESSION, WITH COMPREHENSIVE EVALUATIONS OF DISEASE MARKERS, GUT MICROBIOME ALTERATIONS, AND IMMUNE RESPONSE. THE THIRD OBJECTIVE INVOLVES LABORATORY STUDIES TO DETERMINE THE DIRECT EFFECTS OF TAOS AND LIPID OXIDATION PRODUCTS ON INTESTINAL EPITHELIAL CELLS AND GUT MICROBIOTA, USING BOTH MOUSE-DERIVED AND HUMAN DONOR SAMPLES IN FERMENTATION SYSTEMS TO STUDY MICROBIOME COMPOSITION AND FUNCTION. THESE INTEGRATED APPROACHES AIM TO ELUCIDATE THE MULTIFACETED IMPACT OF TAOS ON GUT HEALTH AND DISEASE MECHANISMS.3. ULTIMATE GOALS AND EXPECTED IMPACTTHE ULTIMATE GOAL OF THIS PROJECT IS TO DELINEATE THE HEALTH RISKS ASSOCIATED WITH THE CONSUMPTION OF TAOS AND TO USE THIS KNOWLEDGE TO INFORM PUBLIC HEALTH GUIDELINES AND COMMERCIAL FOOD PREPARATION PRACTICES. ACHIEVING THESE GOALS CAN LEAD TO SIGNIFICANT HEALTH IMPROVEMENTS, REDUCING THE INCIDENCE OF DIET-RELATED DISEASES SUCH AS GUT DISORDERS AND COLORECTAL CANCER. THIS WOULD NOT ONLY ENHANCE THE QUALITY OF LIFE FOR INDIVIDUALS BUT ALSO LEAD TO ECONOMIC BENEFITS THROUGH DECREASED HEALTHCARE COSTS AND INCREASED PRODUCTIVITY. SOCIETALLY, THE PROJECT AIMS TO RAISE PUBLIC AWARENESS ABOUT THE RISKS ASSOCIATED WITH FRIED FOODS AND,INFLUENCE POLICY CHANGES THAT PROMOTE HEALTHIER FOOD PREPARATION PRACTICES. THESE EFFORTS ARE EXPECTED TO FOSTER A BROADER UNDERSTANDING OF NUTRITION AND HEALTH, ENCOURAGING MORE INFORMED DIETARY CHOICES AND POTENTIALLY LEADING TO NATIONAL AND GLOBAL CHANGES IN FOOD SAFETY REGULATIONS.