针对奶牛增喂精饲料可引发乳腺炎发病率升高但关联机制不明这一临床问题，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，结合课题组已证实乳腺灌注LPS可破坏血乳屏障，降低中性粒细胞跨血乳屏障阈值的研究基础，提出饲料变更等应激因素，导致肠道菌群紊乱，大量“有害菌”滋生，产生过量LPS入血，破坏血乳屏障，增加乳腺炎易感性这一科学假设，展开如下研究：首先构建肠源性亚临床内毒素血症模型，验证肠道菌群紊乱与血中LPS升高的相关性，分析LPS对血乳屏障机能的影响；然后通过病原刺激，检测肠道菌群紊乱时乳腺炎的易感性变化；最后采用宏基因组和代谢组学方法，观测奶牛胃肠道菌群构成、血中LPS浓度与乳腺炎发生的相关性，筛出“有害菌”，揭示肠道菌群紊乱与奶牛乳腺炎易感性增加的关联性机制，从而为探寻相关功能性饲料、微生态制剂和中医药产品研发，开辟奶牛乳腺炎新的防治途径提供研究思路和理论指导

The increased incidence of dairy cattle mastitis can be caused by feeding concentrate. However, the associated mechanism remains unclear. According to the pathomechanism that alterations in intestinal microbiota will lead to subclinical endotoxemia which causes chronic systemic low-grade inflammation, and combined with our previous studies which confirmed that LPS could disrupt the Milk-Blood Barrier and decrease the threshold of neutrophil cross Milk-Blood Barrier, we suggest a scientific hypothesis that stress factors such as feed change could lead to the increases of ‘harmful bacteria’ in the intestines and LPS in blood which disrupts the Milk-Blood Barrier and enhance the susceptibility of mastitis. Therefore, we carried out the following studies: firstly, we validate the relationship between alterations of intestinal microbiota and the increases of blood LPS and analysis the effects of LPS on Milk-Blood Barrier through the model of subclinical endotoxemia. Secondly, we detect the susceptibility of mastitis through the stimulation of pathogenic bacteria. Finally, we detect the relationship between intestinal microbiota and the occurrence of dairy cattle mastitis through metagenomics and metabonomics method to reveal the mechanism of the relativity on increased incidence of dairy cattle mastitis with alterations in intestinal microbiota. This project will provide a valuable theoretical base to develop functional additives, probiotics, and traditional Chinese medicine products and develop new ideas for prevention and treatment of mastitis.