Mechanisms and Implications of Gut Microbiota-Derived Metabolites in the Regulation of Poultry Defensins.

The continuous intensification of modern poultry farming has confronted the industry with a dual crisis involving animal health and food safety. Host defensins, a major class of antimicrobial peptides (AMPs), exhibit broad-spectrum antimicrobial and immunomodulatory activities, demonstrating potential in disease prevention and immune support. By enhancing host innate defense mechanisms, they may complement existing antimicrobial strategies and contribute to reducing antibiotic dependence. Although accumulating evidence highlights the capacity of microbial metabolites to modulate defensin expression, a comprehensive and integrated understanding of the cross-talk between these microbial metabolites and host defensins remains lacking. To bridge this gap, this review summarizes the classification and biological functions of poultry defensins, while synthesizing recent advances in how microbiota-derived metabolites-such as short-chain fatty acids, amino acid derivatives, and secondary bile acids-regulate their expression. By elucidating the underlying receptor-mediated signaling pathways and mechanisms, this review provides strategic insights into leveraging microbial metabolites to stimulate endogenous poultry defensins and offers a reference for the future optimization of immunomodulatory strategies and the improvement of poultry health management.