OBESITY AFFECTS A SIGNIFICANT PROPORTION OF THE U.S. POPULATION AND IS CHARACTERIZED BY ALTERED GUT MICROBIOMES, IMPAIRED CARDIO- AND IMMUNOPROTECTIVE HDL FUNCTIONS, AND PRO-INFLAMMATORY IMMUNE PROFILES, THEREBY INCREASING CHRONIC DISEASE RISK WHILE IMPAIRING IMMUNE DEFENSES. THE GUT MICROBIOME AND ASSOCIATED METABOLOME REGULATE HDL AND IMMUNE PATHWAYS THAT DIFFER BY SEX, AND REPRESENT PROMISING TARGETS TO MITIGATE OBESITY-ASSOCIATED DISEASE. OUR PREVIOUS WORK DEMONSTRATES THAT, COMPARED TO EGG WHITES, WHOLE EGGS IMPROVE HDL, INFLAMMATORY, AND IMMUNE PROFILES TO VARYING DEGREES IN HEALTHY AND METABOLIC SYNDROME POPULATIONS; HOWEVER, IT IS UNKNOWN WHETHER GUT MICROBIOME CHANGES ARE MEDIATING THESE EFFECTS, OR WHETHER THESE EFFECTS ARE SEX-SPECIFIC. THEREFORE, THE LONG-TERM GOAL OF THIS PROJECT IS TO EVALUATE THE GUT MICROBIOME ROLE IN MEDIATING WHOLE EGG EFFECTS ON HDL AND IMMUNE PROFILES BY SEX AND METABOLIC PHENOTYPE. WE WILL CONDUCT A RANDOMIZED CROSSOVER INTERVENTION TRIAL WITH HEALTHY WEIGHT AND OBESITY GROUPS TO TEST OUR HYPOTHESIS THAT, COMPARED TO EGG WHITE INTAKE, WHOLE EGGS WILL PROVIDE GREATER GUT HEALTH-PROMOTING COMPONENTS TO IMPROVE GUT MICROBIOTA COMPOSITION, FECAL AND SERUM METABOLOMES, AND MEASURES OF GUT INFLAMMATION AND INTEGRITY (OBJECTIVE 1); HDL COMPOSITION, EFFLUX AND ANTIOXIDANT CAPACITY, AND IMMUNOMODULATORY FUNCTIONS (OBJECTIVE 2); AND CLINICAL, FUNCTIONAL, AND OMICS-BASED IMMUNE PROFILES (OBJECTIVE 3); AND THAT SEX, METABOLIC PHENOTYPE, AND GUT MICROBIOME PROFILES WILL DICTATE HDL AND IMMUNE RESPONSES TO EGG INTAKE. THIS STUDY DIRECTLY ADDRESSES USDA NIFA FOOD AND HUMAN HEALTH PRIORITIES BY INVESTIGATING THE INTERRELATIONSHIP OF EGGS (AND IMPORTANT U.S. AGRICULTURAL PRODUCT), THE GUT MICROBIOME, AND CHRONIC DISEASE PATHWAYS TO INFORM PERSONALIZED NUTRITION RECOMMENDATIONS THAT SUPPORT HUMAN HEALTH.