基于肠道菌群为靶点探讨燕麦β葡聚糖延缓糖尿病肾病进展的机理研究

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. How to take measures to prevent its development of end-stage renal failure in the early DN is the current hot topic.The preliminary results of the project team by the National Natural Science Foundation of China showed inflammation is a key factor in the development of DN, but only a downstream passage of many mechanisms, not the starting factor. The study found that when intestinal flora uremic toxins fermented by intestinal bacterial flow into the blood circulation, such as endotoxin indoxyl sulphate and sulfuric acid cresol and other harmful substances, causing the body's immune and inflammatory response, mediate a series of kidney damage mechanisms through the activation of monocyte-macrophage system. Thus intestinal flora is originating factor of DN development, and will become the new target for prevention and treatment of DN. Oat β-glucan is a soluble dietary fiber and has a prebiotic effect. We speculated that oat β-glucan intervention in early DN can improve the intestinal microbial environment and thus play a role in delaying the progression of DN. To confirm this hypothesis, the project will evaluate the effect of oat β-glucan on delaying progression of DN effects and its mechanisms through combination of people and animal tests and the use of microbial ecology and metabolomics methods, thus providing science of basis for the effective prevention and treatment of DN.

糖尿病肾病（diabetic nephropathy，DN）是糖尿病最常见的并发症之一, 在DN早期采取措施防止其发展为终末期肾功能衰竭是当前研究热点。本项目组前期国家自然科学基金项目的结果显示炎症反应是DN发生发展的关键因素，但仅仅是众多机制的下游通路，并不是起始因素。研究发现，当肠道菌群失调时肠道细菌发酵产生的内毒素、硫酸吲哚酚和硫酸甲酚等有害物质进入血循环，引起机体免疫炎症反应增强，通过激活单核巨噬细胞系统介导一系列肾损害机制。因此肠道菌群失调是DN发生发展的始发因素，将成为DN防治的新靶点。燕麦β葡聚糖是一种可溶性膳食纤维，具有益生元作用。我们推测在DN早期燕麦β葡聚糖干预可以改善肠道微生态环境从而起到延缓DN进展的作用。为了证实这一假设，本项目通过人群和动物相结合，利用微生物生态学和代谢组学等方法，评价燕麦β葡聚糖对DN进展的延缓作用及机制，为我国DN的有效防治提供科学依据。

糖尿病肾病是糖尿病最常见的并发症之一,在DN早期采取措施防止其发展为终末期肾功能衰竭是当前研究热点。炎症反应是DN发生发展的关键因素，但仅仅是众多机制的下游通路，并不是起始因素。研究发现，当肠道菌群失调时肠道细菌发酵产生的内毒素、硫酸吲哚酚和硫酸甲酚等有害物质进入血循环，引起机体免疫炎症反应增强，通过激活单核巨噬细胞系统介 导一系列肾损害机制。因此肠道菌群失调是DN发生发展的始发因素，将成为DN防治的新靶点。燕麦β葡聚糖是一种可溶性膳食纤维，具有益生元作用。本项目通过人群和动物相结合，利用微生物生态学和代谢组学等方法，评价了燕麦β葡聚糖对DN 进展的延缓作用及机制，我们发现燕麦β葡聚糖能够降低糖尿病大鼠血糖，并延缓糖尿病肾病进展，降低部分炎症因子水平，增加肠道菌群多样性，糖尿病大鼠普氏杆菌丰度增加，燕麦β葡聚糖能够减少普氏杆菌增长，减少胰岛素抵抗，这可能是其延缓糖尿病和糖尿病肾病的机制之一。本项目人群研究显示，燕麦β葡聚糖能够改善糖尿病患者肾脏功能，降低糖尿病患者血糖、血脂和体重，同时对于能够降低血液中炎症相关因子的表达，提高免疫细胞功能，能够增加糖尿病患者肠道菌群多样性。因此本研究结果表明在DN早期燕麦β葡聚糖干预可以改善肠道微生态环境从而起到延缓DN进展的作用，为我国DN的有效防治提供一定的科学依据。