BackgroundAlterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota‐derived metabolites in PD were small‐scale and post‐diagnosis, raising concerns about reverse causality.ObjectivesOur goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.MethodsA nested case–control study within the prospective EPIC4PD cohort, measured pre‐diagnostic plasma microbial metabolites using untargeted metabolomics.ResultsThirteen microbial metabolites were identified nominally associated with PD risk (P‐value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD‐associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals.ConclusionChanges in microbial metabolites may represent a pre‐diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

中文翻译：

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肠道微生物代谢物和帕金森病的未来风险：一项全代谢组关联研究


背景在帕金森病 （PD） 中观察到肠道微生物群的改变。以前关于 PD 中微生物群衍生代谢物的研究是小规模和诊断后的研究，引发了对反向因果关系的担忧。目的我们的目标是在代谢组学框架内前瞻性研究血浆微生物代谢物与 PD 风险之间的关联。方法前瞻性EPIC4PD队列中的一项嵌套病例对照研究，使用非靶向代谢组学测量诊断前血浆微生物代谢物。结果确定了 13 种名义上与 PD 风险相关的微生物代谢物 （P 值 < 0.05），包括氨基酸、胆汁酸、吲哚和羟基酸，尽管在多次测试校正后没有一个仍然显着。PD 风险涉及 3 种途径：缬氨酸、亮氨酸和异亮氨酸降解、丁酸酯代谢和丙酸酯代谢。PD 相关的微生物途径在男性、吸烟者和超重/肥胖个体中更为明显。结论微生物代谢物的变化可能代表 PD 的诊断前特征。我们观察到微生物途径与 PD 之间的生物学上合理的关联，可能受个体特征的影响。© 2024 作者。由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版的《运动障碍》。