APS诱导型微生物生态位调控肉鸡肠道免疫耐受机制

免疫耐受是机体应对内源或外源抗原时所产生的免疫稳态维持和自我保护过程。家禽肠道作为接触外界抗原的最主要场所之一，其微生物区系会对宿主免疫耐受产生重要调控作用，是实现肠道健康稳态的重要基石。团队前期研究发现，黄芪多糖（APS）可诱导肉鸡肠道黏膜免疫耐受样反应。我们认为APS可通过改变微生物生态位诱导机体肠道免疫耐受反应。本项目将通过APS饲粮干预肉鸡在体试验和微生物诱导富集离体试验，结合宏基因组，代谢组和Crispr/Cas9技术，鉴定APS诱导型特异微生物及微生物代谢产物；进而利用LPS肠道应激肉鸡和粪菌移植SPF鸡两个模型，分析调节性T细胞（Tregs）调节的Th1/Th2 型免疫耐受效应分子表达模式，通过靶标物与Tregs共培养离体试验体系，揭示APS诱导型微生物生态位调控肠道免疫耐受的分子机制，阐明其缓解肠道应激的因果应答调控模式，为多糖在家禽健康养殖应用提供有效的理论基础。

Immune tolerance is a process of immune homeostasis maintenance and self-protection in response to endogenous or exogenous antigens. As the main site interacting with external antigens, intestinal microflora plays an important role in immune regulation. However, it is susceptible to dietary regulation in animals. Our previous study found that APS could induce intestinal mucosal immune tolerance in broilers, but the potential mechanism of this phenomenon is still unclear. Thus, based on characteristics of the intestine and its microorganisms mentioned above, we hypothesize that dietary APS induced immune tolerance is regulated by intestinal microorganisms or microbial metabolites. In this project, APS diet intervention in vivo and intestinal microbiota induction enrichment culture in vitro were carried out to identify APS-induced specific microorganisms or microbial metabolites by utilizing metagenomics, metabolomics and CRISPR/Cas9 methods. In addition, the balance of Th1/Th2 immune factors and other targets related to immune tolerance would be analyzed by immunohistochemistry or western blot technique under different conditions including fecal microbiota transplantation, SPF animal models, and co-culture system of bacteria (or its metabolites) and regulatory cells (Tregs). This project will prove whether intestinal immune tolerance regulated by dietary APS is mediated by microbial niche, and further illuminate its immune response to LPS intestinal stress, all of which will provide an effective theoretical basis for the application of polysaccharides in poultry healthy breeding.