Reuterin alleviates broiler intestinal injury against Clostridium perfringens infection via regulating macrophages inflammation

Clostridium perfringens (Cp) is a major zoonotic pathogen consistently linked to significant enteric diseases in poultry, thereby posing serious risks to food safety and public health. Probiotic supplementation is an effective strategy to establish a beneficial gut microbiota, particularly during early life - a critical stage for immune system maturation and intestinal development. This study explores the protective effects of Lactobacillus reuteri 21 (LR21) prenatally administered via in ovo injection against Cp infection in broilers. As a result, LR21 supplementation alleviated the negative effects of the Cp challenge on growth performance, intestinal barrier and inflammation damage. LR21 supplementation also altered the gut microbiota composition and boosted the production of its signature metabolite, reuterin, in Cp-challenged broilers. In vitro, reuterin was able to inhibit the pro-inflammatory responses in macrophages through inhibiting TLR4/MAPK/NF-κB signaling pathway. Based on regulation of macrophages, reuterin also indirectly enhance antioxidant activity of intestinal stem cells to counteract Cp infection, which in turn alleviate intestinal injury. Summarily, this study highlights the potential of LR21 and its metabolite reuterin as a promising intervention strategy to combat enteric pathogens and enhance poultry health and productivity in the face of rising antibiotic resistance.