NECROTIC ENTERITIS (NE) CAUSED BY CLOSTRIDIUM PERFRINGENS INFECTION HAS REEMERGED AS A PREVALENT POULTRY DISEASE WORLDWIDE BECAUSE OF RESTRICTING USAGE OF PROPHYLACTIC ANTIBIOTICS UNDER CONSUMER PREFERENCES AND REGULATORY PRESSURES. IT IS ESTIMATED THAT NE COSTS POULTRY INDUSTRY $6 BILLION EVERY YEAR WORLDWIDE. FEW EFFECTIVE ANTIMICROBIAL ALTERNATIVES ARE AVAILABLE TO PREVENT AND TREAT NE. THE LONG TERM GOAL OF THIS PROPOSAL IS TO IDENTIFY SPECIFIC MICROBIOME AND ITS DOWNSTREAM TARGETS AS EFFECTIVE AND SUSTAINABLE ANTIMICROBIAL ALTERNATIVES TO REDUCE NECROTIC ENTERITIS. OUR PRELIMINARY DATA SHOWED THAT MICROBIOTA METABOLIC PRODUCT DEOXYCHOLIC ACID (DCA) PREVENTED EIMERIA MAXIMA AND C. PERFRINGENS-INDUCED NE, PRODUCTIVITY LOSS, SEVERE INTESTINAL INFLAMMATION, AND CELL DEATH. FOLLOWING MECHANISM STUDIES REVEALED THAT C. PERFRINGENS SPORULATION AND INFLAMMATORY COX SIGNALING DROVE NE DEVELOPMENT AND DCA REDUCED THEM. BASING ON THESE DATA AND CURRENT STATE OF KNOWLEDGE, WE HYPOTHESIZE THAT MICROBIOTA METABOLIC PRODUCT DCA ATTENUATES NE THROUGH REDUCING INFLAMMATORY RESPONSE AND C. PERFRINGENS SPORULATION. IN CURRENT PROPOSAL, WE WILL INVESTIGATE MECHANISM ON HOW INFLAMMATORY SIGNALING PATHWAYS AND C. PERFRINGENS VIRULENCE MODULATE NE OUTCOME AT MOLECULAR LEVELS AND IN CHICKENS. MORE SPECIFICALLY, WE AIM TO IMPLEMENT THE FOLLOWING OBJECTIVES.OBJECTIVE 1: EVALUATE THE CONTRIBUTION OF DCA-ATTENUATED INFLAMMATORY COX-2 SIGNALING ON NE. OBJECTIVE 2: DETERMINE THE ROLE OF DCA-REDUCED C. PERFRINGENS SPORULATION ON NE.UPON COMPLETION, THIS PROJECT COULD SIGNIFICANTLY IMPROVE POULTRY PRODUCTIVITY AND PROVIDE EFFECTIVE AND NEW APPROACHES FOR ANTIMICROBIAL FREE FEEDING REGIMENTS.