Integrated Multi-Cohort Analysis of the Parkinson's Disease Gut Metagenome
Joseph C Boktor1,2, Gil Sharon1, Leo A Verhagen Metman3
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
Background:
The gut microbiome is altered in several neurologic disorders, including Parkinson's disease (PD).
Objectives:
The aim is to profile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression.
Methods:
Shotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n = 48, n = 47, respectively), environmental household controls (HC, n = 29, n = 30), and community population controls (PC, n = 41, n = 49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic data sets from two previous studies in Germany and China to determine generalizable microbiome features.
Results:
We find several significantly altered taxa between PD and controls within the two cohorts sequenced in this study. Analysis across global cohorts returns consistent changes only in Intestinimonas butyriciproducens. Pathway enrichment analysis reveals disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism in PD. Global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted intercommunity signaling.
Conclusions:
A metagenomic meta-analysis of PD shows consistent and novel alterations in functional metabolic potential and microbial gene abundance across four independent studies from three continents. These data reveal that stereotypic changes in the functional potential of the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Insights
The gut microbiome in Parkinson's disease (PD) shows consistent alterations in microbial function and gene abundance across global studies. These findings highlight potential diagnostic and therapeutic targets for PD.
Area of Science:
- Microbiome research
- Neurology
- Genomics
Background:
- The gut microbiome is significantly altered in neurologic disorders like Parkinson's disease (PD).
- Understanding these alterations is crucial for identifying potential diagnostic and therapeutic strategies for PD.
Approach:
- Shotgun metagenomic sequencing was performed on 244 stool donors across two independent US cohorts, including individuals with PD and various control groups.
- Data were cross-referenced with public metagenomic datasets from Germany and China to identify generalizable microbiome features in PD.
Key Points:
- Significantly altered microbial taxa were identified in PD patients compared to controls.
- Pathway analysis revealed disruptions in carbohydrate and lipid metabolism, with increased amino acid and nucleotide metabolism in PD.
- Global gene-level analysis indicated increased oxidative stress response, decreased cellular growth, and disrupted intercommunity signaling in the PD gut microbiome.
Conclusions:
- A metagenomic meta-analysis confirms consistent and novel alterations in the functional metabolic potential and microbial gene abundance of the gut microbiome in PD across four independent studies.
- These stereotypic changes in gut microbiome function are a hallmark of PD, suggesting potential diagnostic and therapeutic avenues.
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