Casein hydrolysate promotes intestinal repair in adult mice with

Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major enteric pathogen that causes severe intestinal damage, characterized by epithelial disruption, inflammation, and impaired regeneration. Nutritional intervention has emerged as a promising strategy to mitigate such injury and promote mucosal repair. Casein enzymatic hydrolysate (CEH) possesses well-documented anti-inflammatory and mucosa-protective properties. However, whether CEH exerts its protective effects against S. Typhimurium-induced intestinal injury by modulating the gut microbiota, and the underlying mechanisms, remains largely unknown. Methods: Twelve-month-old C57BL/6J mice were pretreated with streptomycin and challenged with S. Typhimurium. In the primary efficacy study, mice were assigned to four groups: control, control + CEH, model, and model + CEH (2% CEH in diet for 10 days before and throughout infection). Disease severity, intestinal histology (H&E and PAS staining), inflammation (TNF-α and IL-10 ELISA; CD45 Results: CEH administration significantly improved survival, alleviated clinical disease severity, and attenuated systemic and intestinal inflammation. CEH preserved mucosal architecture, restored goblet cells and barrier proteins (PEPT1, SGLT1, E-cadherin), and promoted LGR5 Conclusion: Collectively, these findings demonstrate that CEH alleviates S. Typhimurium-induced enteritis in adult mice via a microbiota-lactate-GPR81-Wnt3A-ISC axis. CEH represents a promising nutritional strategy to counteract infection-induced intestinal injury and promote regeneration in adult hosts with diminished regenerative reserve.