Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2024-11-12 DOI:10.1002/mds.30054

Yujia Zhao MSc, Yunjia Lai PhD, Sirwan K.L. Darweesh MD, PhD, Bastiaan R. Bloem MD, PhD, Lars Forsgren MD, PhD, Johnni Hansen PhD, Verena A. Katzke PhD, Giovanna Masala MD, Sabina Sieri PhD, Carlotta Sacerdote MD, Salvatore Panico PhD, Raul Zamora-Ros PhD, Maria-Jose Sánchez MD, PhD, José María Huerta PhD, Marcela Guevara MD, PhD, Ana Vinagre-Aragon MD, Paolo Vineis PhD, Christina M. Lill PhD, Gary W. Miller PhD, Susan Peters PhD, Roel Vermeulen PhD

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Abstract

Background

Alterations 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.

Objectives

Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework.

Methods

A nested case–control study within the prospective EPIC4PD cohort, measured pre-diagnostic plasma microbial metabolites using untargeted metabolomics.

Results

Thirteen 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.

Conclusion

Changes 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.

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肠道微生物代谢物与帕金森病的未来风险：全代谢组关联研究

背景在帕金森病（PD）中可观察到肠道微生物群的改变。我们的目标是在代谢组学框架内前瞻性地研究血浆微生物代谢物与帕金森病风险之间的关系。方法在前瞻性 EPIC4PD 队列中进行巢式病例对照研究，利用非靶向代谢组学测量诊断前血浆微生物代谢物。结果发现 13 种微生物代谢物与 PD 风险有名义上的关联（P 值为 0.05），包括氨基酸、胆汁酸、吲哚和羟基酸，但经多重检验校正后，这些代谢物均不显著。有三种途径与腹膜透析风险有关：缬氨酸、亮氨酸和异亮氨酸降解、丁酸代谢和丙酸代谢。男性、吸烟者和超重/肥胖者与帕金森病相关的微生物途径更为明显。我们观察到微生物通路与帕金森病之间存在生物学上合理的关联，这可能受到个体特征的影响。© 2024 作者姓名运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.