Genome-Guided Probiotic Mechanisms of Enterococcus hirae SMU2502: Wnt/β-catenin-Driven Intestinal Epithelial Proliferation and Protection Against Salmonella Infection.

Diarrhea resulting from bacterial infection-induced intestinal injury is a prevalent health concern in animal husbandry. In this study, we explored the potential of bacteriocin-producing probiotics as a preventive strategy. A novel strain of Enterococcus hirae (E. hirae), designated SMU2502 was isolated from goat colostrum and exhibited robust acid and bile salt tolerance and absence of hemolytic activity, supporting its biosafety profile. This strain produces a bacteriocin capable of inhibiting 23 pathogenic bacterial strains, including Escherichia coli (E. coli) ATCC25922, Staphylococcus aureus (S. aureus) ATCC25923, and Klebsiella pneumoniae (K. pneumoniae) ATCC700603. Whole-genome sequencing and functional annotation were employed to infer the metabolic potential of E. hirae SMU2502 and predict host functional targets. These predictions were subsequently validated in vivo. Oral administration of live E. hirae SMU2502 significantly upregulated intestinal expression of Lgr5, Myc, and Ccnd1, and was associated with increased villus length and body weight gain. Furthermore, enhanced intestinal villus proliferation coincided with significant protection against Salmonella infection in vivo, which may also involve bacteriocin-mediated pathogen inhibition, although this mechanism was not directly validated in the present study. These findings demonstrate that E. hirae SMU2502 not only enhances host growth performance but also strengthens intestinal immunity, highlighting its potential as a promising probiotic candidate for mitigating bacterial diarrhea.