RT Journal Article
T1 Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study.
A1 Zhao, Yujia
A1 Lai, Yunjia
A1 Darweesh, Sirwan K L
A1 Bloem, Bastiaan R
A1 Forsgren, Lars
A1 Hansen, Johnni
A1 Katzke, Verena A
A1 Masala, Giovanna
A1 Sieri, Sabina
A1 Sacerdote, Carlotta
A1 Panico, Salvatore
A1 Zamora-Ros, Raul
A1 Sanchez-Perez, Maria-Jose
A1 Huerta, José María
A1 Guevara, Marcela
A1 Vinagre-Aragon, Ana
A1 Vineis, Paolo
A1 Lill, Christina M
A1 Miller, Gary W
A1 Peters, Susan
A1 Vermeulen, Roel
K1 Gut‐brain axis
K1 Microbial metabolites
K1 Parkinson's disease
K1 Pre‐diagnostic biosamples
K1 Untargeted metabolomics
AB 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.
PB Raven Press
YR 2024
FD 2024-11-12
LK https://hdl.handle.net/10668/24332
UL https://hdl.handle.net/10668/24332
LA en
NO Zhao 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.
NO This work was supported by Stichting ParkinsonFonds. Y.Z. received support from the China Scholarship Council during the PhD period at Utrecht University-Institute for Risk Assessment Sciences. S.K.L.D. has received funding from the Parkinson’s Foundation (PFFBS-2026), ZonMW (09150162010183), ParkinsonNL (P2022-07 and P2021-14), The Michael J. Fox Foundation (MJFF-022767), and Edmond J Safra Foundation. C.M.L. was supported by the Heiseberg programme of the Deutsche Forschungsgemeinschaft (DFG; LI 2654/4-1) and by The Michael J. Fox Foundation (MJFF-008994). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the National Institute for Health and Care Research Imperial Biomedical Research Centre (BRC). We are grateful to all the participants who have been part of the project. We acknowledge Dr. Miles Trupp from the Department of Clinical Science, Neurosciences, Umeå University, for his review of the manuscript, particularly for the interpretation on microbial metabolite functions. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France); German Cancer Aid, German Cancer Research Center, German Institute of Human Nutrition Potsdam-Rehbruecke, Federal Ministry of Education and Research (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, National Institute for Public Health and the Environment, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Statistics Netherlands (The Netherlands); Health Research Fund (FIS)— Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, the Catalan Institute of Oncology—ICO, CERCA Program/Generalitat de Catalunya for the institutional support to IDIBELL (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPICOxford), Medical Research Council (MR/N003284/1, MC-UU_12015/1, and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford), University of Cambridge (UK).
DS RISalud
RD Apr 12, 2025