Human Breast Milk‐Derived <i>Lactiplantibacillus plantarum</i> WLPL04 as a Functional Probiotic for Preventing <i>Staphylococcus aureus</i> ‐Induced in Periparturient Mice

This study evaluated the preventive potential of perinatal supplementation with human breast milk-derived Lactiplantibacillus plantarum WLPL04-mCherry to mitigate Staphylococcus aureus infection via prophylactic intervention using a murine mastitis model. Through comprehensive analyses including bacterial enumeration, histopathology, immunohistochemistry, immunofluorescence, and TUNEL staining, we demonstrated that perinatal administration of L. plantarum WLPL04-mCherry significantly reduced S. aureus loads in mammary glands, mesenteric lymph nodes, and liver. The probiotic alleviated S. aureus-induced mammary tissue damage, suppressed neutrophil infiltration and myeloperoxidase activity, downregulated pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and preserved tight junction proteins (Claudin-1, Occludin, and ZO-1), thereby reinforcing the blood-milk barrier and reducing mammary epithelial apoptosis. In vitro co-culture experiments confirmed its direct antagonistic effect against S. aureus through pH-dependent growth inhibition. These findings demonstrate that L. plantarum WLPL04-mCherry prevents S. aureus-induced mastitis through multimodal actions including pathogen inhibition, inflammation modulation, barrier protection, and apoptosis reduction. This study highlights L. plantarum WLPL04 as a promising non-antibiotic preventive agent for perinatal mastitis prophylaxis, offering a sustainable alternative for addressing antibiotic resistance and supporting lactation health.