反刍家畜小肠的食糜及粘膜上皮中栖息着数量庞大的细菌，它们在数量、种类及功能上都存在显著差异。小肠（尤其是空肠、回肠）是机体发生天然免疫应答的重要器官，且很多共生菌的定植可以增强小肠粘膜的屏障功能及天然免疫功能，以防止疾病的发生。探讨小肠细菌的定植与宿主粘膜天然免疫应答的关联机制是研究宿主与细菌相互作用的一个重要方面，而关于这一科学问题的研究目前在反刍家畜上报道较少。本项目拟以山羊为试验动物，研究其在不同发育阶段（非反刍、过渡和反刍阶段），空肠和回肠细菌定植（从出生到反刍功能形成）、分布（食糜和粘膜上皮）与功能演变（代谢产物与代谢通路）规律；解析小肠粘膜天然免疫应答信号通路关键指标的变化规律；并通过整合分析及相关分析阐明小肠细菌定植与粘膜天然免疫应答的关联机制。旨在为研究细菌与宿主的相互作用提供思路，并为反刍家畜各阶段的饲养管理与肠道健康稳衡调控提供科学依据。

Plenty of bacteria, which differ in number, diversity and function, inhabit in the digesta and mucosa of the ruminant small intestine. The small intestine (especially the jejunum and ileum) is the primary organ of innate immune responses, and colonization of most commensal bacteria can enhance intestinal barrier function and innate immune function, playing a key role in the prevention of diseases. Relationship between intestinal bacteria colonization and mucosal innate immune responses is an important part of host-bacteria interaction and this topic has been scarcely reported in ruminants. Therefore, in this project, we use goats at different development phases (non-rumination, transition and rumination phases) as experimental animals. The aims of this study were (1) to investigate age-related bacteria colonization process (diversity, distribution and function) in the jejunum and ileum, (2) to explore changes in jejunal and ileal mucosal innate immune function and related signaling pathway during different development phases, (3) to reveal correlation mechanism of bacteria colonization and mucosal innate immune responses in the small intestine of goats. These results will be helpful to provide new ideas to explore host-bacteria interaction, as well as to establish scientific basis for improving nutrition manipulation and keeping health of the intestinal tracts.