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

Author

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  • Zachary D. Wallen

    (University of Alabama at Birmingham
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

  • Ayse Demirkan

    (University of Surrey)

  • Guy Twa

    (University of Alabama at Birmingham)

  • Gwendolyn Cohen

    (University of Alabama at Birmingham
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

  • Marissa N. Dean

    (University of Alabama at Birmingham)

  • David G. Standaert

    (University of Alabama at Birmingham)

  • Timothy R. Sampson

    (Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network
    Emory University School of Medicine)

  • Haydeh Payami

    (University of Alabama at Birmingham
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

Abstract

Parkinson’s disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association, network analysis to identify polymicrobial clusters, and functional profiling. Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were observed in experimental models; reconcile and resolve human PD microbiome literature; and provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.

Suggested Citation

  • Zachary D. Wallen & Ayse Demirkan & Guy Twa & Gwendolyn Cohen & Marissa N. Dean & David G. Standaert & Timothy R. Sampson & Haydeh Payami, 2022. "Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34667-x
    DOI: 10.1038/s41467-022-34667-x
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