SARA影响锦江黄牛胃肠道微生物和宿主代谢的关联研究

Subacute ruminal acidosis (SARA) is a common metabolic disease observed in ruminants, which changes the gastrointestinal microflora and metabolism of the host. Currently, metagenomics and metabolomics combined with multivariate statistical analysis methods have been proposed as a powerful tool to investigate the relationship between gastrointestinal microbes, host metabolism and disease, however, such methods have rarely reported to apply to the analysis of SARA pathogenesis. In this project, we choose Jinjiang cattle as the experimental animal. By changing the concentrate or physically effective neutral detergent fiber in diet, we construct SARA induced model and compare the dynamic changes of the fermentation parameters and abnormal metabolites in rumen fluid and blood under different inductions. The high-throughput sequencing technology will be used to study the microbial community structure and explore the key factors of difference that presenting between normal feeding group and SARA induced group. Metabolomics analysis of feces and urine will be carried through high performance liquid chromatography quadrupole time of flight mass spectrometry. We try to explore the effect of SARA on metabolism of gastrointestinal microbiota and host, compare metabolic differences between normal feeding group and SARA induced group and identify potential metabolic markers. The current study aims at revealing the internal relationship of SARA affecting gastrointestinal microbes and host metabolism of Jinjiang cattle, and providing a theoretical basis for early diagnosis and SARA pathogenesis for future study.

亚急性瘤胃酸中毒（SARA）是反刍动物常见的一种营养代谢病，它会改变胃肠道微生物区系和宿主代谢。目前，宏基因组学、代谢组学联合多变量统计分析方法是研究微生物、代谢与疾病内在关联的有效手段，但上述方法在SARA发病机制中的研究还鲜见报道。本项目以锦江黄牛为试验动物，改变日粮中精料或物理有效中性洗涤纤维构建SARA诱导模型，比较不同诱导模式对瘤胃液和血液中发酵参数和异常代谢物的动态影响。运用高通量测序技术研究胃肠道中微生物群落结构多样性特点，探究正常饲喂组和SARA诱导组微生物群落结构差异的关键菌群因子。借助超高效液相色谱四级杆飞行时间串联质谱仪对粪便和尿液进行代谢组学分析，探究SARA对胃肠道微生物代谢和宿主代谢的影响，比较正常饲喂组和SARA诱导组之间的代谢差异，寻找代谢标志物，揭示SARA影响锦江黄牛胃肠道微生物和宿主代谢的内在关联，为深入研究SARA早期诊断和发病机制提供理论依据。

本项目以玉米和粉碎苜蓿颗粒成功诱导锦江黄牛亚急性瘤胃酸中毒，以其对瘤胃发酵、微生物区系和宿主代谢的影响为研究目标，研究阐明了不同SARA诱导模式下瘤胃和血液中脂多糖、乳酸、组胺和瘤胃发酵参数的动态变化规律；揭示了常规日粮和不同诱导日粮对瘤胃液和粪便中细菌、真菌等微生物的影响，发现肉牛酸中毒时发生显著变化的微生物类群，并可作为诊断肉牛发生瘤胃酸中毒的微生物标识物。同时，从代谢组学角度揭示了肉牛发生酸中毒和不同诱导方式下机体代谢的差异及对代谢通路的影响，进一步阐明了酸中毒对肉牛胃肠道微生物和宿主代谢的影响机制。本研究成果不仅从微生物和代谢角度研究了肉牛发生亚急性瘤胃酸中毒的发生机制，并为今后深入研究SARA的早期诊断提供了理论依据。