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

Escherichia coli (E. coli) is a major etiological agent of clinical bovine mastitis. This study evaluated the therapeutic potential of Lactobacillus plantarum 17-5 (LP) against E. coli-induced mastitis via clinical, animal, and cellular models. In a trial with mastitic dairy cows, dietary LP significantly reduced systemic inflammatory markers (IL-6, IL-1β, TNF-α) by 2-3-fold (p < 0.05) and milk somatic cell count by 7-fold (p < 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, LP mitigated mammary inflammatory injury (histopathology) and restored tight junction integrity while reducing apoptosis (western blot, p < 0.05). In bovine mammary epithelial cells (BMECs), LP suppressed the cGAS-STING pathway, inhibiting NF-κB P65 phosphorylation and downstream pro-inflammatory cytokine production (p < 0.05). Collectively, LP alleviates E. coli-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.