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Background <p>The rapid emergence of multidrug-resistant <i>Salmonella</i> in poultry demands alternative control strategies beyond conventional antibiotics. In this study, we evaluated a combination of lytic <i>Salmonella</i>-infecting bacteriophages (SLAM_phiST45 and SLAM_phiST56) and a probiotic bacterium <i>Limosilactobacillus reuteri</i> (SLAM_LAR11) in a chick model challenged with <i>Salmonella enterica</i> serovar Typhimurium infection.</p> Results <p>Co-administration with two-phage cocktail and a probiotic showed markedly reduced <i>Salmonella</i> 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 (<i>P</i> &lt; 0.0001) and alleviated infection-associated splenomegaly (<i>P</i> = 0.028) and hepatomegaly (<i>P</i> = 0.011). In the ileum, the villus height-to-crypt depth ratio (VH/CD) increased significantly (<i>P</i> = 0.044). In the colon, expression of tight-junction genes <i>OCLN</i> (<i>P</i> = 0.014), <i>TJP1</i> (<i>P</i> &lt; 0.0001), and <i>MUC2</i> (<i>P</i> = 0.011) was elevated, whereas the pro-inflammatory cytokine <i>IL6</i> was reduced (<i>P</i> = 0.018). These improvements were accompanied, in the cecum, by trends toward decreases in <i>Escherichia–Shigella</i> (<i>P</i> = 0.09) and <i>Clostridium</i> (<i>P</i> = 0.16) and a trend toward an increase in <i>Blautia</i> (<i>P</i> = 0.11); additionally, in the ileum, <i>Lactobacillus</i> (<i>P</i> = 0.037) and <i>Blautia</i> (<i>P</i> = 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.</p> Conclusion <p>Taken together, these findings demonstrate that phage–probiotic co-administration not only enhances the clearance of multidrug-resistant <i>Salmonella</i> 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.</p> Graphical Abstract <p></p>

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Combination of bacteriophage–probiotics alleviates intestinal barrier dysfunction by regulating gut microbiome in a chick model of multidrug-resistant Salmonella infection

  • 期刊论文

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  • 发表日期：

    2026年1月23日

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  • Youbin Choi,
  • Anna Kang,
  • Eunsol Seo,
  • Daniel Junpyo Lee,
  • Junha Park,
  • Yeonsoo Kim,
  • Keesun Yu,
  • Cheol‑Heui Yun,
  • Ki Beom Jang,
  • Woo Kyun Kim,
  • Kwanseob Shim,
  • Darae Kang,
  • Younghoon Kim

摘要

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_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 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