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

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

doi:10.1002/mds.30054

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

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

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
pagine (da-a)	556-560
Numero di pagine	5
Rivista	Movement Disorders
Volume	40
Numero di pubblicazione	3
DOI	https://doi.org/10.1002/mds.30054
Stato di pubblicazione	Pubblicato - mar 2025
Pubblicato esternamente	Sì

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Zhao, Y., Lai, Y., Darweesh, S. K. L., Bloem, B. R., Forsgren, L., Hansen, J., Katzke, V. A., Masala, G., Sieri, S., Sacerdote, C., Panico, S., Zamora-Ros, R., Sánchez, M. J., Huerta, J. M., Guevara, M., Vinagre-Aragon, A., Vineis, P., Lill, C. M., Miller, G. W., ... Vermeulen, R. (2025). Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study. Movement Disorders, 40(3), 556-560. https://doi.org/10.1002/mds.30054

@article{11d22ad1f59f4a189bb753cdc2d02f42,

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

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.",

keywords = "gut-brain axis; microbial metabolites; Parkinson's disease; pre-diagnostic biosamples; untargeted metabolomics",

author = "Yujia Zhao and Yunjia Lai and Darweesh, {Sirwan K.L.} and Bloem, {Bastiaan R.} and Lars Forsgren and Johnni Hansen and Katzke, {Verena A.} and Giovanna Masala and Sabina Sieri and Carlotta Sacerdote and Salvatore Panico and Raul Zamora-Ros and S{\'a}nchez, {Maria Jose} and Huerta, {Jos{\'e} Mar{\'i}a} and Marcela Guevara and Ana Vinagre-Aragon and Paolo Vineis and Lill, {Christina M.} and Miller, {Gary W.} and Susan Peters and Roel Vermeulen",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2025",

month = mar,

doi = "10.1002/mds.30054",

language = "English",

volume = "40",

pages = "556--560",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley & Sons Inc.",

number = "3",

}

Zhao, Y, Lai, Y, Darweesh, SKL, Bloem, BR, Forsgren, L, Hansen, J, Katzke, VA, Masala, G, Sieri, S, Sacerdote, C, Panico, S, Zamora-Ros, R, Sánchez, MJ, Huerta, JM, Guevara, M, Vinagre-Aragon, A, Vineis, P, Lill, CM, Miller, GW, Peters, S & Vermeulen, R 2025, 'Gut Microbial Metabolites and Future Risk of Parkinson's Disease: A Metabolome-Wide Association Study', Movement Disorders, vol. 40, n. 3, pagg. 556-560. https://doi.org/10.1002/mds.30054

TY - JOUR

T1 - Gut Microbial Metabolites and Future Risk of Parkinson's Disease

T2 - A Metabolome-Wide Association Study

AU - Zhao, Yujia

AU - Lai, Yunjia

AU - Darweesh, Sirwan K.L.

AU - Bloem, Bastiaan R.

AU - Forsgren, Lars

AU - Hansen, Johnni

AU - Katzke, Verena A.

AU - Masala, Giovanna

AU - Sieri, Sabina

AU - Sacerdote, Carlotta

AU - Panico, Salvatore

AU - Zamora-Ros, Raul

AU - Sánchez, Maria Jose

AU - Huerta, José María

AU - Guevara, Marcela

AU - Vinagre-Aragon, Ana

AU - Vineis, Paolo

AU - Lill, Christina M.

AU - Miller, Gary W.

AU - Peters, Susan

AU - Vermeulen, Roel

PY - 2025/3

Y1 - 2025/3

N2 - 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.

AB - 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.

KW - gut-brain axis; microbial metabolites; Parkinson's disease; pre-diagnostic biosamples; untargeted metabolomics

UR - http://www.scopus.com/inward/record.url?scp=85208607674&partnerID=8YFLogxK

U2 - 10.1002/mds.30054

DO - 10.1002/mds.30054

M3 - Article

SN - 0885-3185

VL - 40

SP - 556

EP - 560

JO - Movement Disorders

JF - Movement Disorders

IS - 3

ER -

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

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