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Published March 2023 | Supplemental Material + Published
Journal Article Open

Integrated Multi‐Cohort Analysis of the Parkinson's Disease Gut Metagenome


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.

Additional Information

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. We thank Yvette Garcia-Flores for administrative and technical assistance, and Gabriella Sanzo and Alex Yerkan for assistance with patient recruitment and data collection. We thank Dr. Viviana Gradinaru, Dr. Catherine Oikonomou, and members of the Mazmanian laboratory for insightful evaluation of the manuscript. This research was funded in part by the Department of Defense (PD160030) to A.K., and S.K.M., Aligning Science Across Parkinson's (ASAP-020495 and ASAP-000375) through The Michael J. Fox Foundation for Parkinson's Research (MJFF) to S.K.M., and the MJFF (grant no.: 15780) to S.K.M. For the purpose of open access, the author has applied a CC BY 4.0 public copyright license to all author-accepted manuscripts arising from this submission. Author Roles. Design, J.C.B., M.C., A.K., S.K.M.; execution, J.C.B., L.A.V.M., D.A.H., P.A.E., Z.Z., D.L., G.H., G.A.; analysis, J.C.B., G.S., J.O., D.J.H., J.W.B., R.K., S.K.M.; writing, J.C.B., S.K.M.; editing, all authors. Data Sharing. Metagenomic sequencing data are available via Qiita study IDs 14476 and 12975 and EBI-ENA accessions ERP138197 and ERP138199 for TBC and RUMC cohorts, respectively. Sample metadata are available in Table S10. Detailed scripts to reproduce all analysis and data visualization are available at: https://doi.org/10.5281/zenodo.7183678. In addition, we have made an interactive shiny R app available via the link above for exploration of metagenomic features of interest in our data sets (Fig. S6). Full financial disclosures of all authors for the previous 12 months. S.K.M. declares financial interests unrelated to this work in Axial Therapeutics, Nuanced Health, and Seed Health. R.K. declares financial interests unrelated to this work in Biota Technology, GenCirq, DayTwo, Cybele Microbiome, BiomeSense, and Micronoma. L.A.V.M declares financial interests unrelated to this work in Abbott Laboratories, Medtronic, Boston Scientific, AbbVie, Neuroderm, and Avion.

Attached Files

Published - Movement_Disorders_-_2023_-_Boktor_-_Integrated_Multi‐Cohort_Analysis_of_the_Parkinson_s_Disease_Gut_Metagenome.pdf

Supplemental Material - mds29300-sup-0001-supinfo.docx

Supplemental Material - mds29300-sup-0002-figures1.pdf

Supplemental Material - mds29300-sup-0003-figures2.pdf

Supplemental Material - mds29300-sup-0004-figures3.pdf

Supplemental Material - mds29300-sup-0005-figures4.pdf

Supplemental Material - mds29300-sup-0006-figures5.pdf

Supplemental Material - mds29300-sup-0007-figures6.pdf

Supplemental Material - mds29300-sup-0008-tables1.pdf

Supplemental Material - mds29300-sup-0009-tables2.xlsx

Supplemental Material - mds29300-sup-0010-tables3.xlsx

Supplemental Material - mds29300-sup-0011-tables4.xlsx

Supplemental Material - mds29300-sup-0012-tables5.xlsx

Supplemental Material - mds29300-sup-0013-tables6.xlsx

Supplemental Material - mds29300-sup-0014-tables7.xlsx

Supplemental Material - mds29300-sup-0015-tables8.xlsx

Supplemental Material - mds29300-sup-0016-tables9.xlsx

Supplemental Material - mds29300-sup-0017-tables10.xlsx


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Additional details

August 22, 2023
December 22, 2023