摘要Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strate-gies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonello-infecting bacte-riophages(SLAM_phiST45 and SLAM_phiST56)and a probiotic bacterium Limosilactobacillus reuteri(SLAM_LAR11)in a chick model challenged with Salmonella enterica serovar Typhimurium infection.Results Co-administration with two-phage cocktail and a probiotic showed markedly reduced Salmonella colo-nization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In con-trast with phage-only treatment,the combined therapy significantly improved the rate of body-weight change from the day of infection to necropsy(P＜0.0001)and alleviated infection-associated splenomegaly(P=0.028)and hepatomegaly(P=0.011).In the ileum,the villus height-to-crypt depth ratio(VH/CD)increased significantly(P=0.044).In the colon,expression of tight-junction genes OCLN(P=0.014),TJP1(P＜0.0001),and MUC2(P=0.011)was elevated,whereas the pro-inflammatory cytokine IL6 was reduced(P=0.018).These improvements were accompanied,in the cecum,by trends toward decreases in Escherichia-Shigella(P=0.09)and Clostridium(P=0.16)and a trend toward an increase in Blautia(P=0.11);additionally,in the ileum,Lactobacillus(P=0.037)and Blautia(P=0.016)increased significantly,yielding a more balanced microbiota than with phage-only treatment.Consistently,levels of functional metabolites,including acetic acid(LDA=3.32)and lactic acid(LDA=5.29),were increased.Conclusion Taken together,these findings demonstrate that phage-probiotic co-administration not only enhances the clearance of multidrug-resistant Salmonella more effectively than phage treatment alone but also promotes intes-tinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.