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Parkinson's Disease, Gut Microbiota and Plasma Metabolites: Causal Pathways via a Mendelian Randomization Study

Guichun Gong1, Yanran Qian1, Xianjin Tang1

  • 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and School of Medical Information Engineering, Zunyi Medical University, Zunyi, Guizhou, China.

Current Neuropharmacology
|May 21, 2026
PubMed
Abstract

Insights

Gut bacteria like Sellimonas may protect against Parkinson's disease (PD), while the metabolite methylsuccinate appears to increase risk. These findings suggest new targets for understanding PD

Area of Science:

  • Genetics and microbiome research
  • Metabolomics and neurodegenerative disease study

Background:

  • Growing evidence links gut microbiota to Parkinson's disease (PD) pathogenesis.
  • Plasma metabolites are emerging as potential mediators of this gut-brain axis influence.
  • Causal links between gut microbiota, metabolites, and PD phenotypes remain unclear.

Purpose of the Study:

  • To investigate the causal relationships between gut microbiota, plasma metabolites, and Parkinson's disease phenotypes.
  • To determine if plasma metabolites mediate the effects of gut microbiota on PD.
  • To identify specific microbial and metabolic factors influencing PD risk.

Main Methods:

  • Utilized two-sample Mendelian randomization and two-step mediation analyses.
  • Employed genetic instruments from large genome-wide association studies for gut microbiota, metabolites, and PD.
  • Applied False Discovery Rate (FDR) correction and sensitivity analyses for robustness.

Main Results:

  • Genus Sellimonas was identified as a protective factor for PD (OR=0.784, FDR=0.002).
  • Methylsuccinate was identified as a risk metabolite for PD (OR=1.197, FDR<0.001).
  • Exploratory mediation analysis suggested a protective pathway involving Bacillales-methylsuccinate-PD.

Conclusions:

  • Provided genetic evidence for causal links between gut microbiota, plasma metabolites, and PD.
  • Highlighted Sellimonas and methylsuccinate as key factors in PD.
  • Proposed testable hypotheses for gut-brain axis mechanisms in PD pathogenesis.
Keywords:
Parkinson's diseasecausalitygut microbiotamendelian randomizationplasma metabolites

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