肥胖大鼠与肠道菌群相互作用的代谢组学分析

Obesity is a complex metabolic disease resulting from interactions of both genetic and environmental factors causing multiple complications. Symbiotic gut microbiota plays an essential role in the pathophysiology and progressment of obesity. Preliminary study of the applicant have showed that gut microbiota related metabolites changed significantly in the urine of obese rats, such as phenylacetylglycine and 4-hydroxyphenylacetate. This indicates that there are complex interactions between obese rats and gut microbiota. However, the obese host-microbiota interactions are poorly understood. Therefore, in this current project, employing the high-fat diet (HFD) induced obesity rat model, we will investigate the metabonomic changes in rat intestinal tissues and their corresponding contents using nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) techniques. We will also analyze the differences in the gut microbial ecology of intestinal contents using 454 high throughput sequencing technique. Additionally, we will study the correlation between the composition of metabolites and the composition of the gut microbiota in intestinal contents. These findings will enrich our understanding of interactions between obese host and gut microbiota, and provide essential metabonomic information of the pathogenesis and progression of obesity. In this project, we apply metabonomic strategy to applied basic research on the serious diseases. This probably expands new pathway for prevention and treatment of obesity.

肥胖是由基因和环境相互作用引起的一种复杂疾病，发病率高，并发症多且危害严重。肥胖的发生发展与肠道菌群密切相关。申请人的前期研究结果显示，肥胖大鼠尿液代谢组中与肠道菌群相关的代谢物如苯乙酰甘氨酸和4-羟基苯乙酸等发生明显变化，提示肥胖大鼠与肠道菌群之间存在复杂的相互作用。但目前肥胖宿主与肠道菌群的相互作用尚未完全阐明。本项目以高脂饮食诱导的肥胖大鼠为研究对象，拟采用核磁共振和气相色谱质谱相结合的代谢组学检测方法以及454高通量测序技术，通过分析肥胖大鼠肠壁组织和肠道内容物的代谢组，肠道内容物的肠道微生态，以及肠道内容物代谢物组成和肠道菌群组成的相关性，研究肥胖大鼠与肠道菌群的相互作用，为深入了解肥胖的发生发展机制提供重要的代谢组学基础数据。本项目将代谢组学技术应用到重大疾病的应用基础研究中，可能为预防和治疗肥胖提供新的思路。

肥胖是由基因和环境相互作用引起的一种复杂疾病，目前已经严重威胁到人类的健康。为了研究肠道菌群在肥胖发病过程中的作用，我们研究了高脂饮食诱导的大鼠粪样，空肠、回肠、盲肠和结肠各肠壁组织及其内容物的代谢组变化及粪样和肠道内容物中肠道菌群组成的变化。我们进一步将代谢组学数据和宏基因组数据进行整合，找到了代谢物和肠道菌群的相关性。我们发现高脂饮食干预一周便可检测到粪样代谢组的改变，这个变化可以持续到第81天，并且宿主与肠道菌群的共代谢产物发生改变。此外，我们还发现81天的高脂饮食引起了多条代谢途径的改变，包括氨基酸代谢、能量代谢、胆汁酸代谢、胆碱代谢、核苷酸代谢和短链脂肪酸代谢。代谢物和肠道菌群的相关性提示肠道菌群在肥胖的发病过程中起着重要作用。我们的结果丰富了我们对宿主和肠道菌群相互作用的认识，提供了肥胖发病过程中粪样和肠道内容物的代谢组与肠道菌群的变化信息。我们的研究提示粪样和肠道内容物的代谢组和肠道菌群的相关性分析是研究宿主与肠道菌群相互作用的有效方法。