生长猪肠道内微生物与营养代谢互作及其对机体整体代谢作用机制的研究

The proposed project will integrate fields of animal nutrition, biochemistry and gut microbial ecology, and apply techniques including microbial functional genomics and metabolic profiling to investigate the interplay of microbiota and nutrient/ metabolite in the intestine and its impact on the systemic nutritional metabolism of the growing pig. With the most abundant microbiota and highest degree of microbial activity in the pig body, the large intestine will be used as a focus in this study. In vivo and in vitro fermentation experiments will be conducted to assess the response of microbiota and its metabolism to different form and combinations of C and N in the lumen and in turn the influence of microbial activity on the composition and levels of nutrients or metabolites in the lumen will be investigated. To further understand the interaction between microbiota and nutrients, cell culture of pig intestine epithelium will be applied to assess the responsiveness of the nutrient sensing receptors to microbial metabolites. Pigs with intestinal cannula and portal catheters will also be adopted to further investigate the effects of individual or combined metabolites derived from intestinal microbiota on nutrient fluxes, nutrient sensing and whole body metabolism of carbohydrate, nitrogen and fat. The impact of gut microbiota intervention in the pig on the whole body metabolism will be further assessed. Metabolite correlations between intestinal microbe, blood and urine will be deciphered to uncover the metabolic axis between the gut microbiota and the whole body of the pig. Through these, we anticipate to assess the potential of the gut microbiota in directionally manipulating whole body nutritional metabolism of the growing pig, which may provide new frame work guidelines for strategies towards swine production efficiency.

以生长猪为研究对象，以微生物菌群数量最多、代谢最旺盛的大肠为研究器官，结合微生物组学和代谢组学技术，研究大肠微生物及其代谢对肠腔中不同组合碳氮尤其是不同结构的非消化多糖或寡糖等营养素的响应，研究微生物代谢变化对肠腔中营养素及代谢物组成的影响，通过肠上皮细胞培养，研究肠上皮营养素感应受体对不同碳氮组合下的肠道微生物差异代谢物的响应，揭示肠腔内微生物与营养代谢互作机制；结合肠瘘管和血插管技术，研究肠道微生物差异代谢物（单一和混合的）对主要营养素入门脉供应和机体整体代谢的影响；通过回盲肠瘘管灌注抗生素和外源菌或抑制剂等干预大肠微生物代谢，研究微生物差异代谢对机体整体代谢网络的调节，揭示肠道微生物---宿主共代谢互作机制，探析肠道微生物对机体整体水平上的营养代谢调节作用，为定向调节营养代谢进而提高生产效率提供新思路。

以生长猪为研究对象，以微生物菌群数量最多、代谢最旺盛的大肠为研究器官，结合微生物组学和代谢组学技术，研究了大肠微生物及其代谢对肠腔中不同组合碳氮营养素的响应；结合肠瘘管和血插管技术，研究了抗生素、碳氮营养底物等多种方式干预大肠微生物对宿主肠道与机体整体代谢的影响。研究揭示了不同日龄及抗生素干预模式下生长猪肠道微生物菌群结构和代谢的变化规律。研究发现，大肠碳氮底物改变微生物发酵模式，碳源底物发酵产生大量SCFA供机体利用，进而增加了机体能量代谢，促进脂肪酸合成，抑制脂质氧化；而氮源底物增加，产生生物胺和次级胆汁酸，促进糖酵解及脂肪酸氧化，同时增加结肠黏膜炎症反应、降低结肠屏障功能。进一步通过体内体外研究，揭示次级胆汁酸DCA和LCA调节肠道屏障功能的机制。研究还发现，大肠微生物参与调控生长猪下丘脑神经递质表达，而芳香族氨基酸是微生物菌群调控宿主神经功能的重要介质；进一步阐明了芳香族氨基酸在大肠微生物-肠-脑轴中的介导作用机制，并从大肠乳酸杆菌分离了6株芳香族氨基酸代谢利用菌。本项目研究揭示了肠道微生物---宿主共代谢互作机制，探析了肠道微生物对机体整体水平上的营养代谢调节作用，为定向调节营养代谢进而提高生产效率提供新思路。