THE OVERALL GOALS OF THIS PROJECT ARE TO INVESTIGATE THE EFFECTS OF BLACKCURRANT (BC) SUPPLEMENTATION ON CHANGES IN GUT MICROBIOTA AND BONE DENSITY IN POSTMENOPAUSAL FEMALES AND TO ELUCIDATE THE INTERRELATIONSHIP OF BC AND GUT MICROBIOTA ON BONE LOSS MITIGATION BY APPLYING A MULTI-OMICS APPROACH. FOR THIS PURPOSE, WE PROPOSE TO CONDUCT A 3-ARM PARALLEL, DOUBLE-BLIND, RANDOMIZED CONTROLLED TRIAL WITH BC SUPPLEMENTATION FOR 12 MONTHS IN POSTMENOPAUSAL FEMALES AGED 45-70 YEARS. THE PRIMARY ENDPOINTS ARE % CHANGES FROM BASELINE IN WHOLE-BODY, LUMBER SPINE, TOTAL HIP, AND FEMORAL NECK BONE MINERAL DENSITY AT MONTHS 6 AND 12; SECONDARY ENDPOINTS INCLUDE P1NP, RANKL, IL-1Β, TREGS, IGF-1, IGFBP4, RUMINOCOCCUS2, SCFA BUTYRATE, GALLIC ACID, AND PROTOCATECHUIC ACID. THE SPECIFIC OBJECTIVES OF THE STUDY ARE TO INVESTIGATE THE EFFECTS OF BC ON: 1) BONE MASS AND BONE REMODELING MARKERS AND 2) CHANGES IN THE GUT MICROBIOME, IMMUNE AND ENDOCRINE RESPONSES AND THEIR INTERRELATIONSHIPS WITH CHANGES IN BONE MASS; 3) DELINEATE THE INTERPLAY OF BC-GUT MICROBIOTA-BONE THROUGH MICROBIOTA-DERIVED METABOLITES; AND 4) DEVELOP AND VALIDATE AN INTERPRETABLE MACHINE LEARNING ALGORITHM THAT INTEGRATES META DATA AND MOLECULAR DATA TO PREDICT EFFECTIVENESS AND PERSONAL VARIABILITY IN RESPONSE TO BC INTERVENTION. THE PROPOSED STUDY WILL PROVIDE NOVEL INSIGHT INTO WHETHER AND HOW BC REDUCES THE RISK OF POSTMENOPAUSAL BONE LOSS VIA THE GUT-BONE AXIS. FURTHERMORE, DEVELOPING AN ALGORITHM FOR EFFECTIVENESS PREDICTION IN A FOOD-BASED CLINICAL TRIAL WILL PROVIDE A SCIENTIFIC BASIS TO ESTABLISH PERSONALIZED NUTRITION RECOMMENDATIONS AND STRATEGIES FOR ADULT FEMALES' HEALTH AND IDENTIFY WHY METABOLIC HETEROGENEITY EXISTS, WHICH IS CRITICAL FOR FUTURE ADVANCES IN PRECISION NUTRITION.

University Of Connecticut, Storrs CT

Investigators