组合应用NMR代谢组学和16SrDNA测序技术研究肠道菌群调控“肠-脑”代谢稳态参与糖尿病脑病发生发展的时空网络机制

基于1H NMR代谢组学通过对肠道菌相关的菌群代谢物检测，可以反映肠道菌“功能”在特定条件下的变化。这一技术与基于16SrDNA测序的肠道菌多样性分析相结合，有助于从肠道菌“结构”和“功能”上全面探索肠道菌群与疾病发生发展的关系。本项目拟在前期工作基础上开展肠道菌群与机体糖脂代谢调控作用的整合性研究，通过临床对照-动物模型-细胞培养等方法，明确与糖尿病脑病(DE)早期诊断和疾病进展等相关的菌群组成差异及代谢时空变化规律；深入解析调节代谢稳态的菌群-肠-脑轴之间的信息交互机制及协同调控网络，建立肠道菌群通过其关键代谢产物短链脂肪酸参与DE发生发展的代谢调控网络。预期结果将系统建立组合应用基于1H NMR代谢组学和16SrDNA测序技术的肠道菌群调控脑代谢的研究方法，为肠道菌群参与神经系统疾病发生发展提供新的分子机制，同时建立以肠道菌群代谢调控为靶点的健康促进新策略提供理论基础。

1H NMR-based metabonomics can reflect the changes of intestinal bacterial "function" under specific conditions by the detection of microbial metabolites. The combination of this technique and 16SrDNA sequencing analysis of intestinal bacterial diversity is conducive to explore the relationship between the gut microbiota and disease occurrence and development from the "structure" and "function" of intestinal bacteria. Based on our previous work, we attempt to carry out an integrated study on the regulation of intestinal flora and glycolipid metabolism. The differences of microbial composition and temporal and spatial changes of metabolism related to early diagnosis and disease progression of diabetic encephalopathy (DE) will be clarified from clinical, animal, and cellular levels. The cross-talking mechanism between flora, intestine and brain axis is deeply analyzed for regulating metabolic homeostasis. The gut microbiota-regulated metabolic regulation network underlying the occurrence and development of DE will be preliminarily established via its key metabolite short-chain fatty acids in this study. The expected results will elucidate a new molecular mechanism for the role of intestinal flora in the occurrence and development of nervous system diseases, and also provide a theoretical reference for the establishment of a new health promotion strategy by targeting microbial metabolic regulation.