丝氨酸调控新生仔猪肠道SIgA结合菌缓解免疫应激的作用机制研究

新生仔猪因肠道免疫系统发育不健全造成生长受阻和死淘率高，成为制约养猪业可持续发展的瓶颈。肠道分泌型球蛋白A（SIgA）结合菌作为关键调节因子在肠黏膜免疫系统发育过程中发挥主要作用，而丝氨酸（Ser）对维持免疫系统的正常功能至关重要，且申请人前期发现母源Ser可提高哺乳仔猪肠道SIgA分泌和促进肠道有益菌定植。但Ser调控新生仔猪肠道SIgA结合菌缓解免疫应激的分子机制目前尚不清楚。本项目拟通过构建肠道SIgA结合菌细菌流式分选方法，探讨新生仔猪肠道SIgA分泌及其特异性结合菌的变化规律，及Ser对肠道SIgA结合菌的调控作用。结合体内外免疫应激模型和多组学技术，筛选发挥关键作用的差异代谢物、差异菌株和差异基因，揭示Ser调控新生仔猪肠道SIgA结合菌缓解免疫应激的作用机制。本研究将为新生仔猪免疫功能的营养干预提供新的理论依据和手段，同时对提高新生仔猪存活率和养殖生产效率也具有重要现实意义。

The immune system of newborn piglets is not fully developed, which leads to the growth retardation and high mortality rate. This has become a bottleneck restricting the sustainable development of the pig industry. Intestinal secretory globulin A (SIgA)-coated bacteria plays an important role in the development of the intestinal mucosal immune system as a key regulator. Serine (Ser) is very important to maintain the normal function of the immune system and the applicate early found that maternal Ser could improve the secretion of intestinal SIgA and promote the colonization of intestinal microbes in nursing piglets. However, the molecular mechanism by which Ser regulates the SIgA-coated bacteria in piglet intestinal tract to alleviate immune stress is still unclear. This project intends to build a bacterium-flow sorting method for intestinal SIgA-coated bacteria, which is helpful to analyze the change rules of intestinal SIgA secretion and its coated bacteria in newborn piglets and the effect of Ser on intestinal SIgA-coated bacteria. Then, comminating with the immune stress model in vivo and in vitro and multi-omics techniques, differential metabolites, differential strains and differential genes that play key roles are screened，and the regulatory mechanisms of Ser on the alleviation of immune stress via regulating intestinal SIgA-coated bacteria in newborn piglets are further revealed. This study will provide a new theoretical basis and methods for nutritional intervention of immune function in newborn piglets. Meanwhile, it also has important practical significance for improving the survival rate of newborn piglets and the efficiency of breeding production.