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Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms

Zachary D Wallen1,2, Ayse Demirkan3, Guy Twa1

  • 1Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.

Nature Communications
|November 14, 2022
PubMed

Insights

The gut microbiome plays a significant role in Parkinson's disease (PD), with widespread dysbiosis observed in patients. This study reveals how gut bacteria contribute to PD pathogenesis and offers new research avenues.

Area of Science:

  • Microbiology
  • Neuroscience
  • Genetics

Background:

  • Parkinson's disease (PD) is a neurodegenerative disorder with emerging evidence suggesting a gut origin.
  • The gut microbiome's role in PD pathogenesis remains incompletely understood.
  • High-resolution analysis is needed to elucidate specific microbial contributions.

Purpose of the Study:

  • To investigate the gut microbiome's role in Parkinson's disease (PD) at high taxonomic resolution.
  • To identify specific microbial species, genes, and pathways associated with PD.
  • To explore the functional implications of gut dysbiosis in PD.

Main Methods:

  • Large-scale study enrolling 490 PD patients and 234 controls.
  • Deep shotgun sequencing of fecal DNA.
  • Metagenome-wide association studies (MWAS) using ANCOM-BC and MaAsLin2, network analysis, and functional profiling.

Main Results:

  • Over 30% of tested species, genes, and pathways showed altered abundances in PD, indicating widespread dysbiosis.
  • PD-associated species formed interconnected polymicrobial clusters.
  • The PD microbiome exhibited increased pathogens, immunogenic components, and alpha-synuclein pathology inducers, alongside reduced protective factors.

Conclusions:

  • The gut microbiome is significantly altered in Parkinson's disease, contributing to disease permissiveness.
  • Findings reconcile previous studies and provide testable hypotheses for the gut microbiome's role in PD.
  • This research validates experimental findings in human PD and offers a foundation for future investigations.

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