Integrated Multi-Cohort Analysis of the Parkinson’s Disease Gut Metagenome Original paper
Researched by:
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Dr. Umar
ID
Dr. Umar
Read MoreClinical Pharmacist and Clinical Pharmacy Master’s candidate focused on antibiotic stewardship, AI-driven pharmacy practice, and research that strengthens safe and effective medication use. Experience spans digital health research with Bloomsbury Health (London), pharmacovigilance in patient support programs, and behavioral approaches to mental health care. Published work includes studies on antibiotic use and awareness, AI applications in medicine, postpartum depression management, and patient safety reporting. Developer of an AI-based clinical decision support system designed to enhance antimicrobial stewardship and optimize therapeutic outcomes.
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Dr. Umar
Read More
Researched by:
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Dr. Umar
ID
Dr. Umar
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Location
United States of America
Sample Site
Feces
Species
Homo sapiens
What was studied?
This study conducted an integrated, multi-cohort shotgun metagenomic analysis of the gut microbiome in Parkinson’s disease (PD) patients. The primary aim was to characterize alterations in microbial community composition, taxon abundance, metabolic pathways, and microbial gene products, and to explore their associations with PD and disease progression. Stool samples from two large, independent US cohorts were analyzed using shotgun metagenomic sequencing. These results were then cross-referenced with publicly available datasets from two international cohorts (Germany and China) to identify globally consistent microbiome features in PD. The analysis included taxa-level, pathway-level, and gene-level profiles, with comprehensive adjustments for confounding factors such as age, sex, BMI, medication, and household environment.
Who was studied?
The study encompassed 244 stool donors from two independent US cohorts: The BioCollective (TBC) and Rush University Medical Center (RUMC). These included individuals with PD (n=48 TBC, n=47 RUMC), household controls (HC; n=29 TBC, n=30 RUMC), and healthy population controls (PC; n=41 TBC, n=49 RUMC). All PD diagnoses were confirmed by specialists (for RUMC) or self-reported with physician verification (for TBC). Controls were either cohabiting with PD patients (HC) or matched by age, sex, BMI, and race (PC). The study further validated findings using 139 additional samples from two international cohorts in Germany (Bonn) and China (Shanghai), providing a cross-continental meta-analysis. This diverse sample set allowed assessment of generalizable microbiome features despite differences in geography, diet, and collection protocols.
Most important findings
| Key Insight | Details |
|---|
| Microbiome changes in PD | PD is marked by strong functional changes in the gut microbiome, while taxonomic (which bacteria are present) patterns are less consistent between cohorts. |
| Taxa shifts in US cohorts | In US cohorts, PD gut samples were enriched in Actinobacteria, Eisenbergiella tayi, Bifidobacterium bifidum, Akkermansia muciniphila, Ruthenibacterium lactatiformans and depleted in Faecalibacterium prausnitzii, Roseburia, and Eubacterium—key SCFA-producing, anti-inflammatory taxa. |
| Consistent species signal | Across all four cohorts, only one species, Intestinimonas butyriciproducens, was consistently depleted in PD, making it a potential robust microbial marker. |
| Metabolic dysregulation | PD microbiomes showed upregulated genes for pyruvate fermentation, fatty acid synthesis, and amino acid/nucleotide metabolism, with reduced pathways for phospholipid (CDP-diacylglycerol) biosynthesis and vitamin B1/B2 production. |
| Oxidative stress environment | Gene signatures pointed to a gut under oxidative stress, with enrichment of NAD-ubiquinone oxidoreductase and methionine sulfoxide reductase, aligning with PD-related oxidative damage. |
| Impaired growth and signaling | There was reduced cellular growth and motility (loss of flagellar genes) and disrupted microbial communication (depletion of quorum sensing pathways and ABC transporters), indicating a stressed, dysregulated community structure. |
| Link to PD pathophysiology | These functional shifts support an oxidative, inflamed gut environment consistent with PD mechanisms involving neuroinflammation and α-synuclein misfolding. |
| Ties to symptoms and diet | Microbial pathways correlated with disease severity and clinical features (motor progression, olfactory function) and were modulated by diet, including fermented food intake linked to specific taxa and genes. |
Key implications
This comprehensive, cross-cohort meta-analysis demonstrates that PD is characterized by reproducible functional dysbiosis in the gut microbiome, with consistent metabolic and gene-level changes across populations. The identification of robust microbial metabolic signatures—rather than purely taxonomic shifts—suggests that functional profiling may provide more reliable biomarkers for PD diagnosis or progression than species identification alone. The findings highlight the gut microbiome’s potential role in PD pathogenesis, particularly via metabolic disruption and oxidative stress, opening new avenues for microbiome-targeted diagnostics and therapeutics. However, further longitudinal and interventional studies are needed to clarify causality and clinical utility. The study also underscores the importance of harmonized methodologies and metadata collection for microbiome research in neurodegenerative diseases.
Citation
Boktor JC, Sharon G, Verhagen Metman LA, et al. Integrated Multi-Cohort Analysis of the Parkinson’s Disease Gut Metagenome. Mov Disord. 2023;38(3):399-409. doi:10.1002/mds.29300