低CHO/高n-3 PUFA膳食通过重塑肠道菌群防治2型糖尿病的作用与机制研究

2型糖尿病（T2DM）是全球范围内的重大公共卫生问题。研究表明肠道菌群失调是引起T2DM发生发展的重要因素。我们在前期研究中发现低碳水化合物（CHO）/高n-3 PUFA膳食能显著改善DB/DB鼠的血糖水平和胰岛素敏感性，但具体机制尚不明确。本项目结合以往研究发现长期高CHO或高脂膳食摄入可引发肠道菌群紊乱，而膳食结构调整及增加体内n-3 PUFA水平可显著改善上述膳食所致的菌群失调，提出"低CHO/高n-3 PUFA膳食干预能显著改善T2DM患者的血糖调控，该作用的发挥与肠道菌群重塑密切相关"的研究假说，通过运用PCR-DGGE图谱分析、454高通量测序以及系统生物学分析等技术，从人群研究和动物实验两个层面，全面评价以肠道菌群调控为靶点的膳食营养干预在T2DM防治中的作用。本项目对进一步揭示肠道菌群调节与糖尿病发生发展的关系及作用机制，指导居民从膳食途径防治糖尿病具有重要意义。

Type 2 diabetes mellitus (T2DM) is a challenging problem for public health worldwide. Accumulating data shows that the dysfunction of gut microbiota plays an important role in the development and progression of T2DM. In our previous study, we found that the intervention of low carbohydrate (CHO)/high n-3 polyunsaturated fatty acid (PUFA) diet could significantly improve the glucose levels and insulin sentivity of DB/DB mice, yet the mechanisms remained unclear. It has been demonstrated that the long term intervention of high CHO or high fat diet can induce the dysfuction of gut microbiota, while this dysfuction could be substantially alleviated by the dietary structure adjustment or the elevation of endogeneous n-3 PUFA levels. Therefore, we hereby propose the hypothesis that low CHO/high PUFA diet can significantly improve the glycemic control of T2DM patients via the remodelling of gut microbiota. Based on the population intervention and animal study, this project is designed to comprehensively evaluate the effects of dietary intervention on T2DM targeted on gut microbiota regulation, by using the techniques of PCR-DGGE, high throughput sequencing and systematic biology analysis. Our study is of great significance in further clarifying the effects and mechanism of gut mircobiota on T2DM, and also provide scientific evidence for the prevention and treatment of T2DM through the dietary management.