Jin Yuting, Wang Huan, Song Jinan
Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, China.
Front Neurol. 2025 Aug 15;16:1644490. doi: 10.3389/fneur.2025.1644490. eCollection 2025.
The pathogenesis of Parkinson's disease (PD) is gradually evolving from a central neurodegeneration-centered concept to a multi-pathway pathological model at the gut-brain system level. Studies have shown that PD patients commonly exhibit dysbiosis, reduced short-chain fatty acids (SCFAs; microbial fermentation products of dietary fiber that play key roles in host metabolism and immune regulation), abnormal tryptophan metabolism, and impaired gut barrier function. These alterations may contribute to dopaminergic neuronal damage through mechanisms including neuroinflammation, oxidative stress, and α-synuclein (α-syn) aggregation. The vagus nerve plays a critical role in bidirectional gut-brain signaling, and its dysfunction may represent a key route for pathological protein transmission from the periphery to the brain. In response, remote rehabilitation and gut-targeted interventions-including probiotics, prebiotics, dietary modulation, fecal microbiota transplantation (FMT), and transcutaneous vagus nerve stimulation (tVNS)-have shown potential in improving neurological function and inflammation in both animal and clinical studies. Multimodal data analyses have revealed significant associations between SCFA levels in fecal metabolomics and brain imaging features. Despite ongoing challenges in mechanistic extrapolation, biomarker sensitivity, and translational implementation, the integration of metagenomics, metabolomics, neuroimaging, and digital therapeutics-collectively referred to as multi-omics and digital profiling techniques-represents an emerging research direction with the potential to inform future clinical paradigms for precision remote management of PD.
帕金森病（PD）的发病机制正逐渐从以中枢神经退行性变为中心的概念，演变为肠道-脑系统水平的多途径病理模型。研究表明，PD患者通常表现出肠道菌群失调、短链脂肪酸（SCFAs；膳食纤维的微生物发酵产物，在宿主代谢和免疫调节中起关键作用）减少、色氨酸代谢异常以及肠道屏障功能受损。这些改变可能通过神经炎症、氧化应激和α-突触核蛋白（α-syn）聚集等机制导致多巴胺能神经元损伤。迷走神经在肠道-脑双向信号传导中起关键作用，其功能障碍可能是病理性蛋白质从外周向大脑传播的关键途径。相应地，远程康复和针对肠道的干预措施——包括益生菌、益生元、饮食调节、粪便微生物群移植（FMT）和经皮迷走神经刺激（tVNS）——在动物和临床研究中均显示出改善神经功能和炎症的潜力。多模态数据分析揭示了粪便代谢组学中SCFA水平与脑成像特征之间的显著关联。尽管在机制推断、生物标志物敏感性和转化应用方面仍面临挑战，但宏基因组学、代谢组学、神经成像和数字疗法（统称为多组学和数字分析技术）的整合代表了一个新兴的研究方向，有可能为未来PD精准远程管理的临床范式提供依据。
