Gut dysbiosis induces the development of mastitis through reduction of host anti-inflammatory enzyme activity by endotoxemia

In the present study, we found clinical mastitis cows had markedly systemic inflammation, which associated with significant ruminal dysbiosis, especially in enriched Proteobacteria in the rumen. Ruminal microbiota transplantation from mastitis (M-RMT) cow to mouse induced mastitis symptoms in recipient mice, along with increasing mammary pro-inflammatory signatures activation. M-RMT also induced mucosal inflammation and impaired intestinal barrier integrity, leading to increased endotoxemia and systemic inflammation. Moreover, we showed that M-RMT mirrored the ruminal microbiota disruption in the gut of recipient mice, as evidenced by enriched Proteobacteria and similar bacteria functions, which were correlated with most pro-inflammatory parameters and serum LPS level. Recurrent to low-grade LPS mirrored gut dysbiosis-induced endotoxemia and caused severe mastitis in mice. Furthermore, we found gut dysbiosis-derived LPS reduced host alkaline phosphatase by activating neuraminidase (Neu), which facilitates low-grade LPS exposure and E. coli-induced mastitis in mice. Conversely, treating with calf alkaline phosphatase or Neu inhibitor zanamivir alleviated low-grade LPS exposure and E. coli-induced mastitis in mice.