Deoxycholic Acid Mitigates Necrotic Enteritis through Selective Inhibition of Pathobionts and Enrichment of Specific Lactic Acid Bacteria

Necrotic enteritis (NE), caused by Clostridium perfringens, poses significant eco-nomic challenges to the global poultry industry. The increasing ban on in-feed antibiotics in livestock production underscores the need for alternative strategies to combat NE. De-oxycholic acid (DCA), a secondary bile acid, has shown promise in NE mitigation. How-ever, its protective mechanism remains largely unexplored. We employed a 2 * 2 factorial design to investigate the impact of DCA on host response and intestinal microbiome in both healthy and NE-infected chickens. Our results demonstrated that dietary supple-mentation of 1.5 g/kg DCA significantly improved animal survival, reversed growth inhi-bition, and alleviated intestinal lesions. Furthermore, DCA selectively inhibited NE-induced proliferation of C. perfringens and other pathobionts such as Escherich-ia and Enterococcus cecorum. Concurrently, DCA markedly enriched dominant lactic acid bacteria like Lactobacillus johnsonii in both the ileum and cecum of NE-infected chickens. However, DCA had a marginal effect on the jejunal transcriptomic response in both mock- and NE-infected chickens. Therefore, we conclude that DCA protects chicken from NE mainly through targeted inhibition of pathobionts including C. perfringens, with minimum impact on the host. These findings elucidate the protective mechanisms of DCA, support-ing its development as a promising antibiotic alternative for NE mitigation.