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Microbiome signature of Parkinson disease in healthy and genetically at-risk individuals

Title: Microbiome signature of Parkinson disease in healthy and genetically at-risk individuals
Authors: Menozzi, Elisa; Meslier, Victoria; Ren, Yani; Geiger, Mallia; Macnaughtan, Jane; Avenali, Micol; Gilles, Marine; Galandra, Caterina; Mitrotti, Pierfrancesco; Gallo, Luca; Famechon, Alexandre; Lucas del Pozo, Sara; Mezabrovschi, Roxana; Koletsi, Sofia; Loefflad, Nadine; Yalkic, Selen; Limbachiya, Naomi; Blottière, Hervé; Morabito, Christian; David, Aymeric; Quinquis, Benoit; Pons, Nicolas; Valzania, Franco; Cavallieri, Francesco; Fioravanti, Valentina; Toschi, Giulia; Blandini, Fabio; Ehrlich, Stanislav Dusko; Almeida, Mathieu; Schapira, Anthony Hv
Contributors: UCL Queen Square Institute of Neurology; University College London UCL (UCL); MetaGenoPolis (MGP (US 1367)); Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Physiopathologie des Adaptations Nutritionnelles (PhAN); Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Department of Brain and Behavioral Sciences, University of Pavia; IRCCS Mondino Foundation, Pavia; Aligning Science Across Parkinson's Maryland, USA (ASAP); Maurice Wohl Clinical Neuroscience Institut; King‘s College London; Neurology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia; Reggio Emilia Hospital Italy; Azienda USL—IRCCS di Reggio Emilia Reggio Emilia; Alma Mater Studiorum Università di Bologna = University of Bologna Bologne (UNIBO); Department of Brain and Behavioral Sciences, University of Pavia, Pavia; Aligning Science Across Parkinson’s (Grant number:1005 ASAP-000420) through the Michael J. Fox Foundation for Parkinson’s Research (MJFF); EU Joint Programme—Neurodegenerative Research (JPND) through the MRC grant 1007 code MR/T046007/1; ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011)
Source: https://hal.science/hal-05335486 ; 2025.
Publisher Information: CCSD
Publication Year: 2025
Subject Terms: [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Description: Parkinson disease (PD) is a major cause of disability with significant personal and system financial implications . GBA1 variants are the commonest genetic risk factor for PD and increase the risk up to 30-fold. Why only ∼20% of GBA1 variant carriers develop PD remains unknown. Here, by combining clinical and faecal metagenomics data from PD individuals carrying or not GBA1 variants, carriers of GBA1 variants not manifesting PD symptoms (GBA-NMC) and healthy controls, and using an innovative microbiome analysis, we show that a large component of the gut microbiome evolves from healthy across GBA-NMC towards PD and is strongly correlated with disease progression in patients, and prodromal symptoms suggestive of future development of PD in GBA-NMC. By using species altered in PD and GBA-NMC, we detect healthy individuals with the strongest prodromal PD clinical profile. These findings indicate that gut microbiome alterations can identify individuals with GBA1 variants most prone to develop PD and individuals in the general population that may be progressing towards PD. Healthy nutrition mitigates microbiome alterations associated with disease severity, suggesting that it could modify disease progression in PD patients and decrease the risk of disease development in healthy individuals including those with GBA1 variants.
Document Type: report
Language: English
Relation: MEDRXIV: 2025.05.19.25327907
DOI: 10.1101/2025.05.19.25327907
Availability: https://hal.science/hal-05335486; https://hal.science/hal-05335486v1/document; https://hal.science/hal-05335486v1/file/2025.05.19.25327907v1.full.pdf; https://doi.org/10.1101/2025.05.19.25327907
Rights: https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.14712150
Database: BASE