针对奶牛乳腺炎靶向乳腺局部防治效果有限且发病机制久有争议这一现实难题，依据肠道菌群紊乱能导致亚临床内毒素血症并引发机体系统性慢性低度炎症的病理机制，结合本课题组已证实奶牛饲喂过多精料引发系统性炎症反应且伴发乳汁体细胞数显著升高的实验结果，提出奶牛“乳腺炎是机体系统性炎症反应的局部表现”的病理学概念。其理论假设是，饲料变更、泌乳应激等因素造成肠道菌群紊乱，产生的内毒素和/或致病菌损伤肠道屏障并易位入血，引起机体系统性炎症，进而破坏并穿越血乳屏障致发乳腺炎。为此研究如下：首先通过对奶牛乳腺炎的临床实验研究，在临床上验证乳腺炎与肠道菌群紊乱及系统性炎症的关联性；其次通过乳腺炎奶牛粪便移植无菌小鼠实验，揭示肠道菌群紊乱引起机体系统性炎症，进而致发乳腺炎的关联性机制；最后鉴定乳腺炎相关益生菌和有害菌，以期为更深入认识和破解乳腺炎发病机制与防治难题提供新的理论指导和实验依据。

Aiming at the limited problem of localized prevention and treatment of mastitis in dairy cows and the long-term controversy of pathogenesis, according to the pathological mechanism that dysbiosis of gut microbiota can cause subclinical endotoxemia and cause systemic chronic low-grade inflammation, and combined our group previously experiments have confirmed diary cows feeding too much high-concentrate diet causing systemic inflammatory reaction with a significant increase in the number of milk somatic cells, we proposed the following pathological concept and hypotheses "mastitis is a local manifestation of systemic inflammatory response" in dairy cows. The scientific hypothesis is based on the feed changes, lactation stress and other factors leading to dysbiosis of gut microbiota, resulting endotoxin and/or pathogenic bacteria damage the intestinal barrier and transfer to the blood, causing systemic inflammation of the body, and then destroying and crossing the blood-milk barrier cause mastitis. To prove the scientific hypothesis, this project will conduct the following research: firstly, the clinical experiments will be used to verify the relevance between mastitis and dysbiosis of gut microbiota and systemic inflammation. Secondly, we will use fecal microbial transplantation from cow to mouse assay to uncover the associativity of gut microbiota disorder induce systemic inflammation even mastitis; finally we will detect the structure of gut microorganism to identify the probiotics and pathogens associated with mastitis. These data will to provide unprecedented theoretical direction and experiment evidences for the deeply cognition of mastitis pathogenesis and the prevention and cure of mastitis.