帕金森病(PD)是一种普遍的神经退行性疾病,越来越多的证据表明,肠道微生物群的生态失调与PD的发生和进展之间存在联系。在我们之前的调查中,我们发现,在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的PD小鼠模型中,腹膜内施用源自日本糖精的葡甘露聚糖寡糖(GMn)具有神经保护作用。然而,复杂的制备过程,孤立的困难,低产量限制了GMn的进一步勘探。在这项研究中,通过正交实验优化了GMn制备过程中的降解条件。随后,建立了MPTP诱导的PD模型,随后口服GMn。通过逐步优化,我们成功地提高了GMn的产量,从粗岩藻依聚糖中分离出来,从1〜2/10,000到4〜8/1000,表明了改善MPTP引起的运动缺陷的作用,多巴胺神经元的保存,纹状体神经递质水平升高。重要的是,GMn减轻MPTP诱导的小鼠肠道菌群失调。特别是,GM2显着降低了Akkermansia的水平,Verrucomicrobiota,和乳酸菌,与模型组相比,同时促进了Roseburia和Prevotella的丰度。这些发现表明,GM2可以通过调节肠道微生物群来潜在地抑制PD,为开发新型有效的抗PD海洋药物奠定了基础。
Parkinson\'s disease (PD) is a prevalent neurodegenerative disorder, and accumulating evidence suggests a link between dysbiosis of the gut microbiota and the onset and progression of PD. In our previous investigations, we discovered that intraperitoneal administration of glucuronomannan oligosaccharides (GMn) derived from Saccharina japonica exhibited neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. However, the complicated preparation process, difficulties in isolation, and remarkably low yield have constrained further exploration of GMn. In this study, we optimized the degradation conditions in the preparation process of GMn through orthogonal experiments. Subsequently, an MPTP-induced PD model was established, followed by oral administration of GMn. Through a stepwise optimization, we successfully increased the yield of GMn, separated from crude fucoidan, from 1~2/10,000 to 4~8/1000 and indicated the effects on the amelioration of MPTP-induced motor deficits, preservation of dopamine neurons, and elevation in striatal neurotransmitter levels. Importantly, GMn mitigated gut microbiota dysbiosis induced by MPTP in mice. In particular, GM2 significantly reduced the levels of Akkermansia, Verrucomicrobiota, and Lactobacillus, while promoting the abundance of Roseburia and Prevotella compared to the model group. These findings suggest that GM2 can potentially suppress PD by modulating the gut microbiota, providing a foundation for the development of a novel and effective anti-PD marine drug.