肠道菌群介导的猴头菇多糖干预糖脂代谢的调控机制及构效关系研究

Polysaccharides have the function of regulating glucose and lipid metabolism and then intervening type 2 diabetes mellitus. The changes of gut microbiota structure are closely related to metabolic diseases, which may become an important target for their prevention and treatment in the future. Our previous studies have found that Hericium erinaceus polysaccharide has significant effects of lowering blood glucose and lipid, but its structure-function relationship and its interaction mechanism with gut microbiota are still unclear. In view of gut microbiota as the breakthrough point, the present study will be performed in animal model of type 2 diabetes mellitus, with Hericium erinaceus polysaccharide and its acidic and enzymatic hydrolysate as object, by the experimental methods and means of NMR, HPLC-MS, in vitro digestion system, microbial genomics technology, Western blot, qRT-PCR. The study will analyze the effects of different degradation ways on polysaccharide structure , clear the relationship between polysaccharide structure and metabolism of glucose and lipid as well as gut microbiota, and provid a theoretical basis for elucidating the mechanism of Hericium erinaceus polysaccharide in the intervention of glucose and lipid metabolism. It has great scientific significance and broad application prospect in providing new ideas for diet prevention and intervention of type 2 diabetes mellitus, and theoretical basis for the development of functional food of Hericium erinaceus.

多糖具有调节糖脂代谢进而干预2型糖尿病的功能。肠道菌群结构变化与代谢性疾病密切相关，将来可能成为预防及治疗相关疾病的重要靶点。申请人前期研究发现，猴头菇多糖具有显著的降糖降脂功效，但其构效关系及其与肠道微生物的交互作用机制尚不清楚。本项目拟采用2型糖尿病动物模型，以猴头菇多糖及其酸解、酶解产物为研究对象，针对肠道菌群为切入点，通过运用NMR、HPLC-MS、体外模拟消化系统、组学技术、Western blot、qRT-PCR等实验方法和手段，分析不同降解方式对多糖结构和肠道菌群的影响，明确多糖结构与糖脂代谢功能及肠道菌群的关系，为阐明猴头菇多糖干预糖脂代谢的作用机制提供理论依据。本项目可为饮食预防、干预2型糖尿病提供新的思路，为猴头菇相关功能性食品的开发提供理论基础，具有重要的科学意义和广阔的应用前景。

长期的高脂饮食会引起机体糖脂代谢紊乱，进而引发多种慢性疾病。猴头菇是一种药食两用真菌，多糖是其最主要的活性成分之一，具有多种有益健康的生理活性，但是猴头菇多糖通过影响肠道菌群干预糖脂代谢的作用机制尚不清楚。本项目以猴头菇多糖为研究对象，采用化学方法和现代仪器分析手段解析了猴头菇多糖的性质、分子量、单糖组成和糖链单元结构；采用体外消化实验，检测了胃肠消化对猴头菇多糖的影响；通过高脂膳食联合STZ诱导了以糖脂代谢紊乱为主要特征的2型糖尿病小鼠模型，阐明了肠道菌群介导的猴头菇多糖干预糖脂代谢的调控机制。实验结果表明：猴头菇多糖在模拟胃液和小肠液消化过程中发生降解，还原糖含量增加；猴头菇多糖干预提高了糖脂代谢紊乱小鼠肠道有益菌群的丰度，增加了短链脂肪酸的含量，进而影响下游信号通路；通过IRS/PI3K/AKT信号通路促进葡萄糖摄取和肝糖原合成，调节机体糖代谢；通过激活AMPK/SREBP-1c信号通路抑制肝脏脂肪酸合成和减少脂质蓄积；促进肝脏中有益代谢产物的产生。综上所述，猴头菇多糖可通过影响肠道菌群结构调节机体糖脂代谢平衡。研究结果将为猴头菇相关功能食品的开发提供理论依据，也为饮食预防、干预2型糖尿病等代谢性疾病提供新的思路。