Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting...Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting bacteriophages(SLAM_phi ST45 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 colonization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In contrast 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 intestinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded by the National Research Foundation of Korea Grantfunded by the Korean government(MEST)(NRF-2021R1A2C3011051)by the Korea government(MSIT)(No.RS-2023-00218476)。
文摘Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting bacteriophages(SLAM_phi ST45 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 colonization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In contrast 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 intestinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.
