**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PLANT-BASED FOOD PRODUCTS ARE GROWING POPULAR IN THE U.S., AS SHOWN IN A SALES GROWTH OF 31.3% FROM 2017 TO 2019. WITH CONSUMPTION OF RED MEAT STATED BY THE WORLD HEALTH ORGANIZATION'S INTERNATIONAL AGENCY FOR RESEARCH ON CANCER AS 'PROBABLY CARCINOGENIC,' MORE AND MORE POPULATIONS REVEAL A PREFERENCE FOR HEALTHIER DIET OPTIONS OFFERED BY PLANT-BASED MEALS. WHILE NOT ALL PLANT-BASED FOODS CONTAIN HIGH PHYTATE CONTENTS, THE SOY-BASED TEXTURE VEGETABLE PROTEIN--AN EXAMPLE OF THE MOST COMMON MEAT SUBSTITUTE--INCLUDES A RATIO OF PHYTATE TO ZINC OF 25-42.5. THIS RATIO RANGE FAR EXCEEDS THE THRESHOLD OF PREDICTED RATIOS--11.1 AND 15.1 FOR MEN AND WOMEN, RESPECTIVELY--THAT PREVENT PEOPLE FROM ATTAINING THE AMOUNT OF ZINC SATISFYING THE ESTIMATED AVERAGE REQUIREMENT. GIVEN THAT MARGINAL ZINC DEFICIENCY MAY HINDER PROPER GROWTH AND INCREASE RISKS FOR VARIOUS DISEASES, IN ORDER TO DEVELOP STRATEGIES THAT OVERCOME ZINC INADEQUACY RESULTING FROM PHYTATE INTAKE, IT IS CRUCIAL TO BUILD A THOROUGH UNDERSTANDING OF MECHANISMS UNDERLYING THE PHYTATE-INDUCED REDUCTION OF ZINC BIOAVAILABILITY.THE OVERARCHING GOAL OF THIS PROJECT IS TO UNDERSTAND THESE MECHANISMS BY DETERMINING THE EFFECTS OF THE GENES OF HUMAN AND SMALL INTESTINE MICROBIOTA IN ZINC BIOAVAILABILITY ATTENUATED BY PHYTATE. WE RECENTLY IDENTIFIED A NEW PUTATIVE ZINC TRANSPORTER GENE THAT IS ALREADY KNOWN TO REGULATE MYO-INOSITOL, A DEGRADATION PRODUCT OF PHYTATE. BASED ON THIS PRELIMINARY DATA AND EXISTING KNOWLEDGE IN THE ROLE OF MICROBIOTA IN PHYTATE DEGRADATION, WE HYPOTHESIZE THAT THE EXTENT OF PHYTATE DEGRADATION IS REGULATED BY SMALL INTESTINE MICROBIOTA AND THAT THE PRODUCTS OF DEGRADATION, INCLUDING MYO-INOSITOL, IMPACT ZINC BIOAVAILABILITY VIA THEIR INTERACTIONS WITH THE NEW PUTATIVE ZINC TRANSPORTER GENE. TO TEST THESE HYPOTHESES, WE WILL ADOPT GENE MANIPULATION APPROACHES IN INTESTINAL CELL LINES AND MICE AND COMPARE ZINC UPTAKE RATES IN THESE TRANSGENIC CELLS AND ANIMALS VERSUS CONTROLS. ALSO, WE WILL ANALYZE MICROBES IN MICE'S SMALL INTESTINE AND INVESTIGATE ESSENTIAL MICROBES AND THEIR ENZYMES CONTROLLING PHYTATE DEGRADATION AND ZINC ABSORPTION. ALTOGETHER, THIS PROJECT WILL PRODUCE CRITICAL INFORMATION ON THE GENETIC FACTORS DECIDING ZINC BIOAVAILABILITY AND PROMISE FURTHER EXTENSIVE RESEARCH ON IDENTIFYING THE ROLES OF GENETIC VARIANTS IN HOST AND COMMENSAL MICROBES.