Protective effects of total flavonoids of Astragalus combined with Lactiplantibacillus plantarum against Salmonella enterica-challenged intestinal injury in broilers.

Salmonella enterica (SE) challenge compromises growth performance and intestinal health in broilers and is accompanied by intestinal injury, impaired barrier function, inflammatory responses, and gut microbial dysbiosis. Although total flavonoids of Astragalus (TFA) and Lactiplantibacillus plantarum (LP) have each been reported to support intestinal health, their combined effects during SE challenge remain poorly defined. This study investigated the protective effects of TFA combined with LP against SE-induced intestinal injury and explored the potential mechanisms involved. Fifty 1-day-old Arbor Acres broiler chicks were randomly allocated to five groups: Control, SE, TFA, LP, and TFA+LP. Growth performance, diarrhea parameters, ileal morphology, epithelial apoptosis, serum biomarkers, inflammatory cytokines, tight junction-related gene and protein expression, and gut microbiota composition were analyzed. SE challenge impaired growth performance, increased diarrhea rate, and induced intestinal injury. TFA, LP, and their combination alleviated these alterations, with the TFA+LP treatment showing greater efficacy than either individual treatment for selected endpoints. Factorial analysis identified greater-than-additive interactions for VH, IL-1β, Claudin-1 protein abundance, and the positively stained areas of Claudin-1 and ZO-1. Specifically, TFA+LP treatment reduced serum DAO, D-LA, PCT, CRP, TNF-α, IL-1β, and IL-6, increased IL-10, and increased tight junction-related protein expression. Moreover, TFA and LP, alone or in combination, were associated with distinct ileal microbial profiles and differences in selected bacterial taxa. Correlation analysis further showed that selected bacterial genera were associated with growth performance, intestinal barrier status, inflammatory responses, and epithelial apoptosis. TFA and LP, administered alone or in combination, attenuated SE-associated growth impairment and intestinal injury in broilers. The combined treatment produced greater effects than either individual treatment for selected outcomes, although these responses were not uniformly greater than additive effect. These findings support further evaluation of combined TFA and LP administration as a potential strategy for maintaining intestinal health in broilers.