Necrotic enteritis (NE) caused by coccidia and Clostridium perfringens infections 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 $6 billion /year worldwide. Few effective antimicrobial alternatives are available to prevent and treat necrotic enteritis. 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. We plan to fulfill the long term goal with the following objectives. 1) We will evaluate the contribution of DCA-attenuated inflammatory COX-2 signaling on necrotic enteritis. 2) We will determine the role of DCA-reduced C. perfringens sporulation on necrotic enteritis. Upon completion, this project could significantly improve poultry productivity and provide effective approaches for antimicrobial free feeding regiments. The mechanism insight of necrotic enteritis pathogenesis obtained from this project will pave the way for targeted prevention and treatment of this disease.