Goat Bile Acid and Clostridium butyricum Exert a Synergistic Effect in Enhancing the Therapeutic Efficacy Against Diarrhea Induced by Escherichia coli Infection.

The goat industry is a pivotal livestock sector in China, but bacterial diseases severely restrict its sustainable development and production efficiency. Antibiotic overuse in goat farming causes adverse effects and food safety risks, highlighting the urgent need for safe and effective antibacterial functional feed additives. Bile acids are endogenous cholesterol metabolites with hepatoprotective, antioxidative, and intestinal barrier-enhancing functions. They directly inhibit pathogenic Escherichia coli by disrupting bacterial membrane structure and indirectly suppress pathogen colonization via regulating intestinal microflora. Clostridium butyricum maintains intestinal microecological balance, inhibits pathogens by secreting butyric acid to increase intestinal acidity, and promotes intestinal epithelial repair and tight junction protein expression, thereby alleviating -induced intestinal injury, diarrhea and inflammation. Goat bile acid and C. butyricum shows great potential against E. coli-induced diarrhea. Goat bile acid directly suppresses pathogens, while C. butyricum repairs intestinal homeostasis. Their combination provides a comprehensive strategy covering acute pathogen control and long-term mucosal recovery, serving as a promising biological alternative to reduce or replace antibiotics, especially for antibiotic-associated dysbiosis and antimicrobial resistance. This study first established an E. coli-infected mouse model to determine optimal modeling and therapeutic doses. Results showed that 200 mg/kg goat bile acid plus 0.1 g/kg C. butyricum freeze-dried powder significantly alleviated infection-induced damage. A diarrheal goat kid model was further developed, and the combination of a dose of 1.0 g of goat bile acid per kid and a dose of 5.0 g of C. butyricum per kid powder enhanced antioxidant capacity, reduced intestinal inflammation, improved jejunal structure, strengthened intestinal barrier and increased microbiota diversity in goat kids. Consistent beneficial effects were observed in both models. The combination improved jejunal morphology, upregulated mRNA expression of tight junction proteins ZO-1, Occludin and Claudin-1, decreased malondialdehyde content and enhanced superoxide dismutase activity in the liver, jejunum and serum. It also upregulated anti-inflammatory cytokines IL-4 and IL-10, and downregulated pro-inflammatory cytokines IL-1β and TNF-α, with better efficacy than goat bile acid alone.This study confirms that dietary supplementation with goat bile acid and C. butyricum effectively protects goat kids against E. coli infection, providing a practical approach for ruminant health management and helping reduce antibiotic dependence in commercial goat farming.