糖尿病大鼠肠道菌群演替特征及与宿主相互作用在疾病发生发展中的作用研究

项目名称： 糖尿病大鼠肠道菌群演替特征及与宿主相互作用在疾病发生发展中的作用研究

项目编号： No.81200583

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 吴晓康

作者单位： 西安交通大学

项目金额： 23万元

中文摘要： 近来发现，肠道菌群作为宿主"内化器官"在肥胖症和2型糖尿病的发生中起到重要作用。本课题组前期工作发现，2型糖尿病患者与健康人群肠道菌群的结构特征比较存在显著差异，菌群的组成、多样性和相似性发生改变。目前肠道菌群在糖尿病发生发展过程中的演替特征及与宿主相互作用在疾病发生中的意义还不明确。本项目采用PCR-DGGE、454测序、荧光定量PCR等方法，动态观察糖尿病大鼠肠道菌群结构变化特征、宿主的代谢功能和炎症状态；并分析糖尿病宿主代谢紊乱对肠道微环境和菌群结构特征的影响。采用抗生素和益生菌对肠道菌群结构干预，通过对模式识别受体（TLRs、NLRs）、局部黏膜屏障、细胞免疫和代谢功能等检测，观察菌群改变对宿主免疫和代谢功能的影响。本课题意在揭示肠道菌群随宿主疾病演替规律，阐明肠道菌群结构变化与宿主代谢功能、代谢性炎症及胰岛素抵抗发生的相关性，为寻找2型糖尿病新的治疗靶点提供依据。

中文关键词： 2型糖尿病；肠道菌群；演替特征；模式识别受体；炎症

英文摘要： It has been recently discovered that gut microbiota, as a host"organ", has exerted great influence in the development of obesity and metabolic disease. From the preliminary work of our research group, it has been found that by comparing the structural characteristics of gut bacteria between type 2 diabetics and healthy people, there exists a significant difference, for instance, shift occurs in the diversity, similarity and the composition of microbiota. At present, it is not clear about succession characteristics of gut microbiota in the development of diabetes and the significance of the mutual interaction between the host and gut microbiota in the development of the disease. By adopting the methods like PCR-DGGE, 454 sequencing, Fluorescence quantitative PCR and so on, the dynamic monitoring will be carried out to observe the structural changes of gut microbiota in diabetic rats and the metabolic function and inflammation state of the host, and to analyze the influence of the metabolic disturbance of diabetes host on intestinal microenvironment and structural characteristics of microbiota. By adopting antibiotics and probiotics to intervene in the microbiome composition, through the detection of several indexes, such as various types of pattern recognition receptor (TLRs、NLRs), Local mucous membrane barrier,

英文关键词： Type 2 diabetes；Gut microbiota；Succession characteristics；Pattern-recognition receptor；Inflammation