Introduction

Research has suggested a link between the gut microbiota and Parkinson’s Disease (PD), and an early involvement of gastrointestinal dysfunction has been reported in patients. A mechanism review was performed to investigate whether the neurodegenerative cascade begins in the gut; mediated by gut dysbiosis and retrograde transport of α-synuclein. This review provides a summary of microbiome composition associated with PD, and evaluates pathophysiological mechanisms from animal and in vitro models of PD.

Method

A systematic literature search was performed in PubMed; 82 of 299 papers met the inclusion criteria.

Results

All twenty-two human case-control studies demonstrated an altered gut microbiota in PD compared to healthy controls, with results suggesting a proinflammatory phenotype present in PD. A germ-free animal study has demonstrated that gut microbiota are required for microglia activation, α-synuclein pathology and motor deficits. Accumulation of phosphorylated α-synuclein has been observed in the enteric nervous system prior to the onset of motor symptoms in animal models of PD, and there is data to support retrograde transport of α-synuclein from the gut to the brain. Different animal models of PD have demonstrated neuroinflammation, microglial activation and loss of dopaminergic neurons in the brain.

Conclusion

Evidence from this review supports the hypothesis that pathology spreads from the gut to the brain. Future animal studies using oral LPS or microbiota transplants from human PD cases could provide further insight into the entire mechanism. Prospective longitudinal microbiome studies and novel modelling approaches could help to identify functional dysbiosis and early biomarkers for PD.

中文翻译：

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肠道菌群与帕金森病之间的联系：系统性机制综述，重点关注 α-突触核蛋白转运

介绍

研究表明肠道微生物群与帕金森病 (PD) 之间存在联系，并且据报道，患者早期会出现胃肠道功能障碍。进行了机制审查以研究神经退行性级联反应是否始于肠道；由肠道菌群失调和α-突触核蛋白逆行转运介导。本综述总结了与 PD 相关的微生物组组成，并评估了 PD 动物和体外模型的病理生理机制。

方法

在 PubMed 中进行了系统的文献检索；299 篇论文中有 82 篇符合纳入标准。

结果

与健康对照组相比，所有 22 项人类病例对照研究均表明 PD 中的肠道微生物群发生了改变，结果表明 PD 中存在促炎表型。一项无菌动物研究表明，小胶质细胞激活、α-突触核蛋白病理学和运动缺陷需要肠道微生物群。在 PD 动物模型中，在运动症状发作之前，已在肠神经系统中观察到磷酸化 α-突触核蛋白的积累，并且有数据支持 α-突触核蛋白从肠道逆行转运到大脑。不同的 PD 动物模型已经证明了大脑中的神经炎症、小胶质细胞激活和多巴胺能神经元的丧失。

结论

这篇综述的证据支持病理学从肠道传播到大脑的假设。未来使用人类 PD 病例的口服 LPS 或微生物群移植的动物研究可以进一步了解整个机制。前瞻性纵向微生物组研究和新的建模方法可以帮助识别功能失调和 PD 的早期生物标志物。