肠道菌群通过SCFAs/GPCRs免疫途径对小鼠帕金森模型神经保护的机制研究

越来越多的研究报道肠道菌群失衡与帕金森病（PD）的发病相关。利用粪菌移植（FMT）技术能够纠正PD的肠道菌群失衡，改善PD运动功能障碍和脑内神经递质减少、多巴胺能神经元缺失现象。短链脂肪酸是肠道菌群的主要代谢物，对机体免疫应答具有极其重要的调节作用。我们前期研究发现，PD小鼠体内SCFAs含量异常升高，而FMT治疗后均明显降低。研究表明，G蛋白偶联受体激活是SCFAs影响机体免疫应答的主要作用方式。基于上述，我们提出假设：肠道菌群通过细菌代谢物调控机体免疫应答进而改善小鼠PD症状，而这一调控作用可能是通过SCFAs/GPCRs通路的活性与功能变化介导的。我们利用基因敲除动物模型，将验证SCFAs是否通过结合GPRs发挥免疫调节作用进而改善PD症状。该研究结果将揭示FMT如何通过免疫途径影响机体免疫应答进而改善PD症状的作用机制。

A growing number of studies have reported that gut dysbacteriosis is associated with the onset of Parkinson's disease (PD). The dysbacteriosis, motor dysfunction, decrease of neurotransmitter, loss of dopaminergic neurons could be greatly improved by fecal bacteria transplantation (FMT) technique in our previous study. Short chain fatty acids (SCFAs) is the major metabolite of gut microbiota, which plays an important role in regulating immune response. In our previous work, It was intersting that abnormally elevated content of SCFAs in PD mice was significantly reduced after FMT treatment. Besides, Combination with G protein-coupled receptors (GPCRs) is the major way that mediates the immune regulation effect of SCFAs in host. Therefore, we hypothesized that gut microbiota influence MPTP-induced Parkinson's disease model mice through SCFAs/GPCRs related immune pathway. Gene defective animal models will be applied to verify whether SCFAs can improve PD by combining GPRCs with immune regulation. This project will reveal possible mechanisms of FMT improve PD symptoms by immune pathway.