仔猪肠黏膜先天性免疫系统是其抵抗病源微生物的第一道防线。申请者选育了一株罗伊氏乳杆菌，测定了其全基因序列，且研究发现其能显著改善仔猪肠道抗氧化和黏膜免疫功能、减少病原微生物感染。本项目以罗伊氏乳杆菌为模式菌，以新生和断奶仔猪为动物模型，在前期工作基础上，通过与美国俄克拉荷马州立大学深入合作，采用微生物宏基因组学、蛋白质组学、代谢组学及生物信息学等技术，研究罗伊氏乳杆菌调控仔猪肠道微生物菌群结构的变化规律，探索其介导的肠道营养素和微生物菌群代谢产物对肠黏膜先天性免疫系统的激活作用，揭示差异化日粮营养素及菌群代谢产物调节肠黏膜先天性免疫的靶基因及其调控网络通路，从根本上阐明乳酸杆菌调控猪肠道微屏障功能的机制，为益生菌安全性和有效性体内体外评价模型的建立、优良乳酸菌株的筛选与分子改良以及微生物制剂质量标准的制定提供理论依据，对微生物制剂的安全和规范使用，对提高国产微生物制剂的国际竞争力意义重大。

The intestinal innate immune system is the first line of host defense against invading pathogens in piglets. The applicants selected a strain of Lactobacillus reuteri and determined its entire gene sequence. Previous studies from our lab have suggested that supplementation of Lactobacillus reuteri is critical to improve porcine intestinal anti-oxidation and mucosal immune function and to reduce the infections. Based on these discoveries and through intensive collaborations with Oklahoma State University in the US and with Lactobacillus reuteri as the bacterial model and neonatal and weanling piglets as the animal models, and with the cutting-edge approaches associated with metagenomics, proteomics, metabolomics and bioinformatics, the objectives of this project are to investigate the pattern of Lactobacillus reuteri on gut microbiota regulation, the change in nutrient metabolites and microbial metabolites, and the target genes and regulation network between these metabolites and intestinal innate immune function in piglets. These researches will systemically illustrate the mechanism of Lactobacillus reuteri on the regulation of intestinal innate immune function in piglets. Our studies will provide a solid theoretical basis for selection, genetic modification, and safety and efficacy evaluation for beneficial Lactobacillus strains as well as for establishing the quality control standards for other probiotics, which is of great significance for the safety and standardization utilization of the microbial preparation, and for improving the international competitiveness of domestic microbial preparation.