**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CHRONIC INFLAMMATION IS AN IMPORTANT FEATURE OF CARDIOMETABOLIC DISEASES, INCLUDING CARDIOVASCULAR DISEASE, THE MAJOR CAUSE OF MORBIDITY AND MORTALITY IN THE U.S. CHRONIC INFLAMMATION OCCURS WHEN THE BODY'S ABILITY TO RESOLVE INFLAMMATION IS WEAKENED. THE RESOLUTION OF INFLAMMATION IS PROMOTED BY LIPID MOLECULES DERIVED FROM THE OMEGA-3 FATTY ACIDS EPA AND DHA PRESENT IN FISH AND FISH OIL AND CALLED SPECIALIZED PRO-RESOLVING LIPID MEDIATORS (SPMS). WESTERN DIET HAS BEEN SHOWN TO CAUSE ALTERATIONS IN GUT MICROBIOTA COMPOSITION AND FUNCTION, INFLAMMATION, AND CARDIOVASCULAR DISEASE BOTH IN HUMANS AND IN MICE. HOWEVER, WHETHER OMEGA-3 FA-DERIVED SPMS CAN PREVENT THE WESTERN DIET-INDUCED ALTERATIONS IN GUT MICROBIOTA IS CURRENTLY NOT KNOWN. OUR STUDY WILL DETERMINE THE IMPACT OF THE CHANGES IN GUT MICROBIOTA CAUSED BY OMEGA-3 FA-DERIVED SPMS ON INFLAMMATION AND ATHEROSCLEROSIS BY USING MICE THAT LACK THE ENZYME INVOLVED IN THE CONVERSION OF OMEGA-3 FATTY ACIDS TO SPMS. BY COMPARING THE EFFECTS ON GUT MICROBIOTA AND INFLAMMATION IN CONTROL MICE AND IN MICE THAT CANNOT PRODUCE SPMS RECEIVING OMEGA-3 SUPPLEMENTATION, OUR STUDY WILL PROVIDE IMPORTANT KNOWLEDGE ON THE ROLE OF SPMS ON GUT MICROBIOTA AND LEAD TO THE DEVELOPMENT OF THERAPEUTIC INTERVENTIONS FOR THE PREVENTION OF GUT MICROBIOTA ALTERATIONS, INFLAMMATION, AND CARDIOMETABOLIC DISEASES.