Abstract 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 (SLAMₚhiST45 and SLAMₚhiST56) and a probiotic bacterium Limosilactobacillus reuteri (SLAMLAR11) 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. Graphical Abstract
Choi et al. (Fri,) studied this question.