鼠李糖乳杆菌GG对犊牛腹泻致肠黏膜免疫屏障功能紊乱的调控机制

犊牛养殖是我国畜牧业重要组成部分。新生犊牛免疫系统发育不完善，极易受病原体侵袭导致腹泻，继发出现肠道屏障功能紊乱，严重造成死亡。抗生素常用于治疗犊牛腹泻，但残留和耐药性问题相继使其在世界范围内被限制或禁止使用。益生菌对调控动物肠道健康具有重要意义。鼠李糖乳杆菌GG（Lactobacillus rhamnosus GG，LGG）耐受胃酸及胆汁，并表现出对肠粘膜上皮细胞较强亲和力，有极大潜力促进犊牛肠道健康，预防腹泻。本项目首先通过断奶前犊牛饲养试验构建腹泻模型，利用16S rRNA测序结合非靶向代谢组学技术研究LGG对犊牛腹泻致肠道菌群失衡和肠粘膜免疫功能紊乱的调控作用；随后利用体外细胞分离培养结合细胞信号转导技术，探究LGG基于TLRs-MyD88通路调控COX-2/CXCL12/CXCR4轴实现对犊牛肠粘膜免疫屏障功能调控的作用机制，为LGG在畜牧生产中的应用提供理论依据。

Calves rearing is an important part of animal husbandry in China. Newborn calves are vulnerable to diarrhea caused by pathogen before the maturation of immune system, which secondary result in intestinal barrier dysfunction and even death. Antibiotics were commonly used to treat diarrhea of calves, but their use is restricted or prohibited worldwide due to residues and drug resistance. Probiotics play an important role in regulating the intestinal health of animals. Lactobacillus rhamnosus GG shows a great potential to promote intestinal health and prevent diarrhea due to its resistance to gastric acid and bile and strong affinity to intestinal mucosal cells. In current study, the diarrhea model of preweaning calves will be established in the feeding experiment, and the effects of LGG on the alleviation of intestinal flora imbalance and intestinal mucosal immune dysfunction will be studied using 16S rRNA sequencing combined with metabonomic methods. Subsequently, cell isolation and culture in vitro combined with cell signal transduction technique will be used to elucidate the role of LGG in modulating intestinal mucosal immune barrier function based on TLRs-MyD88 signaling pathway modulating COX-2/CXCL12/CXCR4 axis, and to unveil the mechanism of LGG alleviating the intestinal mucosal immune dysfunction in calves, which would provide a theoretical basis for the development and application of LGG in the livestock production.