ENDING THE USE OF ANTIBIOTIC GROWTH PROMOTERS (AGPS) CREATES CHALLENGES FOR THE ANIMAL FEED AND FEED ADDITIVE INDUSTRIES. DEVELOPING EFFECTIVE ALTERNATIVES TO AGPS IS URGENTLY REQUIRED IN ORDER TO MAINTAIN CURRENT ANIMAL PRODUCTION LEVELS WITHOUT THREATENING PUBLIC HEALTH. BASED UPON OUR RECENT FUNCTIONAL MICROBIOME WORK ANDEMERGING UNDERSTANDING OF INTERACTION BETWEEN BACTERIAL BILE SALT HYDROLASE (BSH) AND HOSTIN THE INTESTINE, WE HYPOTHESIZE THAT DIETARY SUPPLEMENTATION OF BSH INHIBITORS COULD PROMOTE HOST LIPID METABOLISM AND ENERGY HARVEST, CONSEQUENTLY ENHANCING FEED EFFICIENCY AND BODY WEIGHT GAIN IN POULTRY. TO TEST THIS, WE PLAN TO 1) EVALUATE IDENTIFIED BSH INHIBITORS IN A WELL-SIMULATED CHICKEN EXPERIMENTAL SYSTEM; 2) UNDERSTAND THE MECHANISTIC BASIS OF BSH INHIBITORS THROUGH ANALYSIS OF EX VIVO SAMPLES; AND 3) UNDERSTAND BSH STRUCTURE-FUNCTION RELATIONSHIPS AND STRUCTURE-BASED DESIGN OF BSH INHIBITORS.THE OUTCOMES OF THE PROJECT WILL LEAD TO THE DEVELOPMENT OF INNOVATIVE ALTERNATIVES TO AGPS FOR THE USE IN POULTRY AND POSSIBLY OTHER LIVESTOCK. THIS PROJECT WILL NOT ONLY FILL SIGNIFICANT KNOWLEDGE GAPS IN BASIC SCIENCE OF BSH ENZYMES BUT ALSO IMPROVEPUBLIC HEALTHAND REDUCE THE DEPENDENCE ON AGPS WHILE MAINTAINING ANIMAL PRODUCTIVITY AND SUSTAINABILITY.