Succinate exacerbates mastitis in mice via gut microbiota-derived extracellular vesicles

Abstract Background Ecological imbalance of the gut microbiota may be an important endogenous trigger of mastitis, but the underlying mechanisms are unclear. Recent findings indicated that selected bacteria of the maternal gastrointestinal microbiota can reach the mammary gland through an entero-mammary pathway. In addition, metabolic disturbances are one of the most prominent ways in which gut dysbiosis promote distal organ diseases. Results In the present study, we found that Gastrointestinal-associated mastitis showed significant changes in metabolic levels, among which succinate was significantly increased. In addition, succinate treatment exacerbates endotoxemia-induced mastitis in mice. Meanwhile, succinate induced intestinal ecological dysregulation. Further experiments demonstrated that succinate increased the production of extracellular vesicles containing gut microbial (mEVs) lipopolysaccharides, which could diffuse across the damaged intestinal barrier into the mammary glands. mEVs promotes mammary inflammation mainly through activation of the TLR4/NF-κB pathway. Conclusions Our findings suggest that succinate promotes mastitis through proliferatio of enteric pathogens and mEVs production, suggesting a potential strategy for mastitis intervention based on intestinal metabolic regulation and pathogen inhibition. The role of mEVs in interspecific communication has also been elucidated.