ALZHEIMER'S DISEASE (AD), A CHRONIC, PROGRESSIVE, AND PRESENTLY INCURABLE CONDITION, AFFECTING MILLIONS OF AMERICANS. THIS PROJECT'S CENTRAL HYPOTHESIS IS THAT BLUEBERRY-DERIVED NANOCOMPONENT EXOSOMES (BBDEXO) CAN MODULATE MICROBIOTA METABOLITES, INHIBIT GUT INFLAMMATION, AND ALLEVIATE COGNITIVE IMPAIRMENT THROUGH THE MICROBIOTA-GUT-BRAIN (MGB) AXIS. THE LONG-TERM GOAL IS TO CREATE A PRECISE AND PERSONALIZED BLUEBERRY NUTRITION PLAN TO MITIGATE THE SYMPTOMS EXPERIENCED BY AD PATIENTS BASED ON THEIR SPECIFIC GUT MICROBIOME.OBJECTIVE 1 IS TO EVALUATE THE PROTECTIVE IMPACT OF BBDEXO ON BIOACTIVES DURING GUT TRANSIT AND ITS PHARMACOLOGICAL ACTIVITIES. WE WILL ASSESS THE STABILITY AND RELEASE OF DIETARY BIOACTIVES FROM BBDEXO IN SIMULATED GI FLUIDS, AND EXPLORE CELLULAR UPTAKE AND EFFICACY IN TARGETED MICROBIOTA, GUT, AND BRAIN CELLS. OBJECTIVE 2 AIMS TO INVESTIGATE THE INFLUENCE OF BBDEXO ON THE MGB AXIS IN MOUSE MODELS TRANSPLANTED WITH AD PATIENT MICROBIOTA. THE EFFECTS OF BBDEXO ON MICROBIOTA COMPOSITION, MICROBIOTA RELATED METABOLIC PROFILES, GUT FUNCTIONALITY, GUT PRODUCTION OF NEUROACTIVE MOLECULES, BRAIN INFLAMMATION, AND COGNITIVE FUNCTION IN MICE WILL BE EVALUATED.THIS PROJECT, ALIGNING WITH PROGRAM AREA A1343 FOOD AND HUMAN HEALTH, INTENDS TO DEEPEN OUR UNDERSTANDING OF BLUEBERRY'S BENEFICIAL EFFECTS ON THE MGB AXIS AND LAY THE GROUNDWORK FOR DEVELOPING TARGETED INTERVENTIONS. IT HAS THE POTENTIAL TO SUBSTANTIALLY CONTRIBUTE TO THE FIELD OF PRECISION NUTRITION AND PUBLIC HEALTH.