帕金森病中的肠-脑轴：从临床观察到基于机制的精准医学

文献信息

中文摘要

背景： 胃肠道功能障碍日益被认为是帕金森病（PD）的核心特征，影响生活质量、营养、药物反应，并可能涉及发病机制的最早期阶段。本视角文章追溯了肠道从被忽视的非运动症状来源，演变为PD生物学模型核心组成部分的过程。方法：胃肠道表现具有生理异质性，需要客观表型分析以区分吞咽困难、胃轻瘫、慢传输、排便功能障碍及重叠机制。结果：身体优先/大脑优先框架进一步提示，路易病理可能沿不同的解剖轨迹发展，早期肠神经系统和自主神经受累定义了一个亚组，在该亚组中肠道导向的生物标志物和治疗可能尤为相关。肠道微生物组的改变与PD可重复地相关，尽管地理、便秘、药物、饮食、疾病阶段和反向因果使解读复杂化。新兴研究正从分类学转向微生物功能和宿主通路，包括屏障完整性、免疫和肠内分泌信号、短链脂肪酸、胰高血糖素样肽-1（GLP-1）、宿主遗传易感性、α-突触核蛋白聚集和传播，以及微生物左旋多巴代谢。结论：益生菌、粪菌移植和饮食干预的试验仍异质性较大，尚未确立疾病修饰疗效。进展将需要在前驱期和亚型定义人群中进行纵向研究、客观胃肠道测量、整合微生物、宿主遗传及其他多组学、机制性人类和动物模型，以及结合靶点参与标志物与有意义结局的临床试验。这种方法可能为适当选择的PD患者实现精准肠-脑医学。© 2026 作者。Movement Disorders 由 Wiley Periodicals LLC 代表国际帕金森和运动障碍学会出版。

英文摘要

Gastrointestinal dysfunction is increasingly recognized as a core feature of Parkinson's disease (PD), affecting quality of life, nutrition, medication response, and potentially the earliest stages of pathogenesis. This perspective traces the evolution of the gut from a neglected source of non-motor symptoms to a central component of biological models of PD. Gastrointestinal manifestations are physiologically heterogeneous and require objective phenotyping to distinguish dysphagia, gastroparesis, slow transit, defecatory dysfunction, and overlapping mechanisms. The body-first/brain-first framework further suggests that Lewy pathology may follow distinct anatomical trajectories, with early enteric and autonomic involvement defining a subgroup in which gut-directed biomarkers and therapies may be especially relevant. Alterations of the gut microbiome are reproducibly associated with PD, although geography, constipation, medication, diet, disease stage, and reverse causation complicate interpretation. Emerging work is shifting from taxonomy toward microbial functions and host pathways, including barrier integrity, immune and enteroendocrine signaling, short-chain fatty acids, glucagon-like peptide-1 (GLP-1), host genetic susceptibility, α-synuclein aggregation and propagation, and microbial levodopa metabolism. Trials of probiotics, fecal microbiota transplantation, and dietary interventions remain heterogeneous and have not established disease-modifying efficacy. Progress will require longitudinal studies in prodromal and subtype-defined populations, objective gastrointestinal measurements, integrated microbial, host-genetic and other multi-omics, mechanistic human and animal models, and clinical trials combining target-engagement markers with meaningful outcomes. Such an approach may enable precision gut-brain medicine for appropriately selected patients with PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.