Lactobacillus plantarum 17-5 Alleviates Escherichia coli Mastitis by Inhibiting the cGAS-STING Pathway

<i>Escherichia coli</i> (<i>E. coli)</i> is a major etiological agent of clinical bovine mastitis. This study evaluated the therapeutic potential of <i>Lactobacillus plantarum</i> 17-5 (<i>LP</i>) against <i>E. coli</i>-induced mastitis via clinical, animal, and cellular models. In a trial with mastitic dairy cows, dietary <i>LP</i> significantly reduced systemic inflammatory markers (IL-6, IL-1β, TNF-α) by 2-3-fold (<i>p</i> < 0.05) and milk somatic cell count by 7-fold (<i>p</i> < 0.05). 16S rRNA sequencing revealed these improvements were associated with substantial gut microbiota restructuring, suggesting a link between gut microbial balance and mammary health via the gut-mammary axis. In a murine model, <i>LP</i> mitigated mammary inflammatory injury (histopathology) and restored tight junction integrity while reducing apoptosis (western blot, <i>p</i> < 0.05). In bovine mammary epithelial cells (BMECs), <i>LP</i> suppressed the cGAS-STING pathway, inhibiting NF-κB P65 phosphorylation and downstream pro-inflammatory cytokine production (<i>p</i> < 0.05). Collectively, <i>LP</i> alleviates <i>E. coli</i>-associated mastitis by modulating gut microbiota through the gut-mammary axis and directly inhibiting the cGAS-STING/NF-κB axis, supported by multi-model evidence.