Zhao, YujiaLai, YunjiaDarweesh, Sirwan K LBloem, Bastiaan RForsgren, LarsHansen, JohnniKatzke, Verena AMasala, GiovannaSieri, SabinaSacerdote, CarlottaPanico, SalvatoreZamora-Ros, RaulSanchez-Perez, Maria-JoseHuerta, José MaríaGuevara, MarcelaVinagre-Aragon, AnaVineis, PaoloLill, Christina MMiller, Gary WPeters, SusanVermeulen, Roel2024-11-252024-11-252024-11-12Zhao Y, Lai Y, Darweesh SKL, Bloem BR, Forsgren L, Hansen J, et al. Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study. Mov Disord. 2024 Nov 12.https://hdl.handle.net/10668/24332Background 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Gut‐brain axisMicrobial metabolitesParkinson's diseasePre‐diagnostic biosamplesUntargeted metabolomicsParkinson DiseaseMicrobiotaGastrointestinal Microbiomeresearch article39530417open accessEnfermedad de ParkinsonMicrobioma GastrointestinalDiagnósticoIsoleucina10.1002/mds.300541531-8257