** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** WORLDWIDE, 18.3% OF THE POPULATION 50 YRS OF AGE AND OLDER HAVE OSTEOPOROSIS, AND WOMEN ARE FOUR TIMES MORE LIKELY TO BE AFFECTED THAN MEN. THE PRIMARY CULPRIT, POSTMENOPAUSAL BONE LOSS, IS NOW RECOGNIZED AS AN INFLAMMATORY DRIVEN PROCESS THAT INTERFERES WITH NORMAL BONE CELL ACTIVITY. THE DECLINE IN ESTROGEN THAT OCCURS WITH MENOPAUSE BRINGS ABOUT PHYSIOLOGICAL CHANGES IN THE IMMUNE SYSTEM WHICH IF LEFT UNCHECKED RESULTS IN SIGNIFICANT BONE LOSS. DESPITE THE DEVELOPMENT OF DRUGS TARGETING THE BONE TO TREAT OSTEOPOROSIS, ADHERENCE TO THESE PHARMACOLOGICAL REGIMENS REMAINS POOR. STUDIES USING LABORATORY ANIMALS POINT TO SPECIALIZED IMMUNE CELLS (I.E., T CELLS) AS THE PRIMARY CELL THAT IS RESPONSIBLE FOR THESE NEGATIVE EFFECTS ON BONE. A LARGE PROPORTION OF A PERSON'S T CELLS CAN BE FOUND AT ANY ONE TIME WITHIN THE LINING OF THE INTESTINE. THESE CELLS CAN LEAVE THE INTESTINE AND TRAVEL TO OTHER PARTS OF THE BODY SUCH AS BONE. T CELLS IN THE INTESTINE ARE AFFECTED BY THE FOODS THAT WE EAT AND BY THE MICROORGANISMS THAT RESIDE WITHIN THE INTESTINE (I.E., GUT MICROBIOTA). OUR PRELIMINARY DATA SHOW THAT DRIED PLUMS ACT AS PREBIOTICS WHICH HAVE POTENT EFFECTS ON THE GUT MICROBIOTA AND ALTER T CELL FUNCTION IN LABORATORY MODELS OF POSTMENOPAUSAL OSTEOPOROSIS. CLINICAL WITH POSTMENOPAUSAL WOMEN HAVE CLEARLY DEMONSTRATED THAT SUPPLEMENTING THE DIET WITH DRIED PLUMS PREVENTS POSTMENOPAUSAL BONE LOSS. YET, TO DATE NO COMPREHENSIVE STUDY OF THE EFFECTS OF DRIED PLUMS ON IMMUNE FUNCTION IN HUMANS HAS BEEN UNDERTAKEN. THE GOAL OF THIS PROJECT IS TO DETERMINE THE EXTENT TO WHICH THESE GUT-MEDIATED, T CELL RESPONSES OBSERVED IN ANIMAL MODELS TRANSLATE TO IMPROVING IMMUNE FUNCTION IN POSTMENOPAUSAL WOMEN. BECAUSE OF THIS POPULATION'S RISK FOR SUBOPTIMAL VITAMIN D STATUS AND VITAMIN D'S EFFECTS ON T CELLS, WE WILL ALSO EXPLORE HOW VITAMIN D STATUS AFFECTS THE RESPONSE TO DRIED PLUM. TO ACCOMPLISH THIS, WE WILL RECRUIT POSTMENOPAUSAL WOMEN TO PARTICIPATE IN A 10-WEEK CROSSOVER STUDY (I.E., 4 WKS WITH AND 4 WKS WITHOUT DRIED PLUM WITH 2 WEEKS IN BETWEEN). WE WILL DETERMINE THE INFLUENCE OF DRIED PLUMS ON 1) IMMUNE (T CELL) FUNCTION AND 2) THE GUT MICROBIOTA AND GUT-DERIVED METABOLITES; AND (3) INVESTIGATE HOW VITAMIN D STATUS AFFECTS THESE RESPONSES. WE ANTICIPATE THAT THIS PROJECT WILL PROVIDE ADVANCE OUR UNDERSTANDING OF HOW SUPPLEMENTING THE DIET WITH FOODS THAT HAVE PREBIOTIC ACTIVITY COULD BE USED TO IMPROVE IMMUNE FUNCTION IN WOMEN. BECAUSE OF THE ROLE OF THE IMMUNE SYSTEM IN MANY DISEASES THAT DISPROPORTIONATELY AFFECT WOMEN, THIS WORK COULD HAVE IMPLICATIONS THAT EXTEND BEYOND IMPROVING BONE HEALTH TO OTHER DISEASES (E.G., AUTOIMMUNE DISEASES, CARDIOVASCULAR DISEASE, AND CERTAIN CANCERS.) FURTHERMORE, POSITIVE FINDINGS RELATED TO THIS STUDY COULD IMPACT GROWERS AS WELL AS THE DRIED PLUM INDUSTRY MORE BROADLY.