Breed-driven bile acid metabolic heterogeneity highlights the potential of UDCA as an anti-inflammatory food additive

In the field of animal nutrition and food production, developing efficient and safe food additives to improve animal health and enhance disease resistance is crucial for improving food quality and safety and reducing antibiotic reliance. This study investigates the potential of ursodeoxycholic acid (UDCA) as a novel functional food additive in Min pigs and Yorkshire pigs using an LPS-induced inflammatory model. Min piglets showed strong disease resistance with stable organ coefficients and normal histological activity indices, exhibiting immune tolerance with no significant changes in pro-inflammatory cytokines in the liver and ileum. In contrast, Yorkshire pigs were highly sensitive to LPS-induced inflammation, showing increased cytokines, disrupted tight junction proteins, and gut-liver axis dysregulation. Metabolomic analysis revealed that Min piglets effectively modulated serum bile acid levels and maintained gene expression related to bile acid enterohepatic circulation, preserving gut-liver axis stability. After LPS challenged, UDCA levels relative-increased in Min pigs, negatively correlating with pro-inflammatory factors and indicating a potential protective role, whereas Yorkshire pigs showed downregulated bile acid cycle genes and no UDCA increase. Experiments further demonstrated that UDCA significantly alleviated hepatic and intestinal inflammation in an LPS-induced mouse model. In summary, Min pigs develop a unique disease-resistant nutritional metabolic pattern through stable bile acid enterohepatic circulation and the immunomodulatory effects of UDCA. These results demonstrate that UDCA has promising application potential as a functional additive to alleviate inflammatory responses and maintain gut-liver axis homeostasis. Furthermore, it indicates that UDCA possesses the potential to reduce antibiotic usage in the prevention and treatment of livestock inflammation and to support the development of safe food additives, ultimately contributing to the safety and quality of food.