Study on diarrhea-induced gut microbiota dysbiosis increasing susceptibility to Staphylococcus aureus-induced mastitis in mice and the intervention mechanism of chlorogenic acid
Mastitis is a major disease affecting livestock production worldwide and is frequently accompanied by diarrhea in dairy cows. Emerging evidence has demonstrated a close association between mastitis and gut microbiota dysbiosis; however, whether diarrhea influences the development of mastitis through alterations in the gut microbiota remains unclear. In this study, we found that diarrhea increased the susceptibility of mice to Staphylococcus aureus induced mastitis. Antibiotic depletion and fecal microbiota transplantation experiments further demonstrated that this effect was dependent on the gut microbiota. Integrated 16S rRNA gene sequencing and untargeted metabolomics analyses revealed that diarrhea disrupted gut microbial homeostasis and reduced the abundance of chlorogenic acid. Further investigation showed that chlorogenic acid alleviated susceptibility to S. aureus-induced mastitis by restoring blood-milk barrier integrity and reducing the levels of pro-inflammatory cytokines. Mechanistically, CGA enhanced the phagocytic capacity of macrophages by activating the PI3K/AKT signaling pathway and upregulating Rac1 protein expression, thereby ameliorating mastitis. Collectively, these findings indicated that diarrhea-induced alterations in the gut microbiota enhance susceptibility to S.au-induced mastitis in mice. CGA supplementation strengthens the antimicrobial defenses of the mammary gland, providing novel therapeutic perspectives for mastitis associated with intestinal dysbiosis.