TO EFFECTIVELY MITIGATE ANTIMICROBIAL RESISTANCE IN THE AGRICULTURAL ECOSYSTEM, THERE IS AN INCREASING PRESSURE TO REDUCE AND ELIMINATE THE USE OF IN-FEED ANTIBIOTICS FOR GROWTH PROMOTION AND DISEASE CONTROL IN FOOD ANIMALS. HOWEVER, LIMITING ANTIBIOTICS COULD COMPROMISE PRODUCTION EFFICIENCY AND ANIMAL HEALTH. THUS, DEVELOPING EFFECTIVE ALTERNATIVES TO ANTIBIOTICS IS URGENTLY NEEDED. BUILDING UPON OUR ACCUMULATIVE RESEARCH EFFORTS ON FUNCTIONAL MICROBIOME AS WELL AS MODULATION OF HOST INNATE IMMUNITY, WE HAVE DEVELOPED TWO TYPES OF INNOVATIVE SMALL MOLECULES, NAMELY BILE SALT HYDROLASE INHIBITORS AND HOST DEFENSE PEPTIDE-INDUCING COMPOUNDS, AS ALTERNATIVES TO ANTIBIOTICS FOR GROWTH PROMOTION AND DISEASE CONTROL IN POULTRY. IN THIS PROPOSAL, WE PROPOSE TO USE INNOVATIVE AND COST-EFFECTIVE ENCAPSULATION TECHNOLOGIES TO FURTHER IMPROVE THE EFFICACY OF THESE NATURAL COMPOUNDS FOR COMMERCIAL APPLICATIONS. WE ALSO WILL DEVELOP EFFECTIVE EXTENSION AND EDUCATION PROGRAMS WHICH ARE HIGHLY INTEGRATED WITH RESEARCH TO ENCOURAGE ADOPTION OF INNOVATIVE NON-ANTIBIOTIC STRATEGIES. THE PROPOSED WORK WAS DEVELOPED WITH SIGNIFICANT INPUTS FROM STAKEHOLDERS AND RECEIVED ENTHUSIASTIC SUPPORT FROM THE INDUSTRY. THIS MULTI-DISCIPLINARY PROJECT WILL BE CONDUCTED BY A HIGHLY QUALIFIED MULTI-INSTITUTIONAL TEAM WITH MAJOR PARTICIPANTS FROM TWO USDA EPSCOR INSTITUTIONS. THE OUTCOMES OF THE PROJECT WILL LEAD TO THE DEVELOPMENT OF TWO INNOVATIVE NON-ANTIBIOTIC FEEDING TECHNOLOGIES FOR IMMEDIATE ADOPTION AND COMMERCIALIZATION IN POULTRY AND POSSIBLY OTHER LIVESTOCK, THUS MITIGATING ANTIMICROBIAL RESISTANCE ACROSS THE FOOD CHAIN.