粪菌移植联合中药对肥胖幼鼠肠道菌群—短链脂肪酸—GPR43—胃肠肽通路的影响及作用机制研究

Obesity and its related disorders are harmful to physical and mental health of children, but the treatment effect is not as well as expected. Researches showed that the gut microbiota were dynamically correlated with human obesity. And we have found that high fat diet(HFD) induced young mice were with gut microbiota altering. Fecal microbiota transplantation (FMT) can modulate gut microbiota successfully as a therapy. All above come up with hypothesises: HFD induced young obese mice would be with gut microbiota and its downstream metabolites altering, FMT combined with Chinese medicine Fang Feng Tong Sheng granule may effectively modulate gut microbiota-Short Chain Fatty Acids(SCFAs)-GPR43-gastrointestinal peptides. In this research three studies will be processed:1. A systemic review about the therapeutic effect and safety of FMT on treating obesity--a Meta analysis based on clinical trials and animal experiments. 2. Exploring the impact of obesity fecal microbiota transplanting to normal mice by intestigating the gut microbiota-SCFAs-GPR43-gastrointestinal peptides(PYY/GLP-1/GAS/MTL) pathway. 3. Exploring the impact of FMT cooperating/contrasting with Fang Feng Tong Sheng granule to young obese mice by intestigating the gut microbiota-SCFAs-GPR43-gastrointestinal peptides(PYY/GLP-1/GAS/MTL) pathway. This should be an initiative study to investigate the therapeutic benefits and mechanisms of FMT combined with Chinese medicine on childhood obesity, which will contribute to providing new treatment and experience on childhood obesity.

肥胖及其并发症严重危害儿童身心健康，且治疗效果不佳。现代发现肥胖与肠道菌群及其代谢产物失调相关。申请者前期研究表明高脂饮食幼鼠出现肠道菌群失调。粪菌移植是调整肠道菌群的有效治疗手段。故提出假说：高脂饮食诱导的肥胖幼鼠可出现肠道菌群及其下游代谢产物失调；粪菌移植联合防风通圣颗粒可能通过影响肠道菌群—短链脂肪酸—GPR43—胃肠肽通路对肥胖幼鼠产生保护作用。本研究拟开展：1.粪菌移植治疗肥胖的疗效与安全性系统评价—基于临床试验与动物实验的Meta分析。2.肥胖粪菌对正常幼鼠肠道菌群—短链脂肪酸—GPR43—胃肠肽（PYY/GLP-1/GAS/MTL）通路影响的实验研究。3.粪菌移植联合/比较防风通圣颗粒对肥胖幼鼠肠道菌群—短链脂肪酸—GPR43—胃肠肽（PYY/GLP-1/GAS/MTL）通路影响的实验研究。本研究领先开展中药联合粪菌治疗儿童肥胖的效果并探索其机制，为儿童肥胖提供新疗法及依据。

肥胖及其并发症严重危害身心健康，且治疗效果不佳。现代研究发现肥胖与肠道菌群及其代谢产物失调相关，而高脂饮食因素与肠道微生态的失衡关系密切。本项目即从文献研究和实验研究两个方面展开，文献研究通过整理粪菌移植的国内外最新进展，为后续系统评价研究提供依据及参考；采用系统评价的方法对粪菌移植治疗肥胖进行定性描述，评价粪菌移植治疗肥胖的疗效与安全性；采用系统评价再评价的方法评价代谢综合征各治疗措施系统评价的方法学质量及其结局指标的可靠程度。实验研究通过饲喂高脂饮食建立肥胖大鼠模型，探索肥胖粪菌对正常大鼠肠道菌群—短链脂肪酸—GPR43—胃肠肽通路影响；探索粪菌移植联合/比较防风通圣颗粒对肥胖大鼠肠道菌群—短链脂肪酸—GPR43—胃肠肽通路影响。高脂饮食可引起肠道菌群失调，短链脂肪酸代谢障碍，引发代谢下游机制启动，GPR43作为下游通路中的一个重要环节，影响胃肠肽的表达，从而影响肠上皮细胞的完整性，导致机械屏障受损，黏膜通透性改变。粪菌移植联合中药可纠正菌群失调，影响“肠道菌群—短链脂肪酸—GPR43—胃肠肽”通路而对高脂饮食模型大鼠产生保护作用，为肥胖提供新的治疗方向和依据。

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