Metagenomics of the Gut Microbiome in Parkinson's Disease: Prodromal Changes
Open accessAbstract
Objective: Prior studies on the gut microbiome in Parkinson's disease (PD) have yielded conflicting results, and few studies have focused on prodromal (premotor) PD or used shotgun metagenomic profiling to assess microbial functional potential. We conducted a nested case–control study within 2 large epidemiological cohorts to examine the role of the gut microbiome in PD. Methods: We profiled the fecal metagenomes of 420 participants in the Nurses' Health Study and the Health Professionals Follow‐up Study with recent onset PD (N = 75), with features of prodromal PD (N = 101), controls with constipation (N = 113), and healthy controls (N = 131) to identify microbial taxonomic and functional features associated with PD and features suggestive of prodromal PD. Omnibus and feature‐wise analyses identified bacterial species and pathways associated with prodromal and recently onset PD. Results: We observed depletion of several strict anaerobes associated with reduced inflammation among participants with PD or features of prodromal PD. A microbiome‐based classifier had moderate accuracy (area under the curve [AUC] = 0.76 for species and 0.74 for pathways) to discriminate between recently onset PD cases and controls. These taxonomic shifts corresponded with functional shifts indicative of carbohydrate source preference. Similar, but less marked, changes were observed in participants with features of prodromal PD, in both microbial features and functions. Interpretation: PD and features of prodromal PD were associated with similar changes in the gut microbiome. These findings suggest that changes in the microbiome could represent novel biomarkers for the earliest phases of PD. ANN NEUROL 2023;94:486–501
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A nested case-control study utilizing two large epidemiological cohorts showed that a microbiome-based classifier had moderate accuracy in discriminating and identifying prodromal and early PD patients according to gut microbiome profile.
“One example of an approach that provided temporal insight into the progression of the gut microbiome at different stages of PD comes from a nested case–control study utilizing two large epidemiological cohorts. This study showed that a microbiome-based classifier had moderate accuracy in discriminating and identifying prodromal and early PD patients according to gut microbiome profile [134].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [134]
Cites
Multivariable association discovery in population-scale meta-omics studies
Mallick, H., Rahnavard, A., McIver, L. J., Ma, S., Zhang, Y., Nguyen, L. H., Tickle, T. L., Weingart, G., Ren, B., Schwager, E. H., et al. (2021) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1009442 · Cited by 2,596 · see citing works
Self-citationGut microbiota are related to Parkinson's disease and clinical phenotype
Scheperjans, F., Aho, V., Pereira, P. A. B., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola‐Rautio, J., Pohja, M., et al. (2015) · Movement Disorders · doi:10.1002/mds.26069 · Cited by 1,968 · see citing works
Metagenomic microbial community profiling using unique clade-specific marker genes
Segata, N., Waldron, L., Ballarini, A., Narasimhan, V., Jousson, O., & Huttenhower, C. (2012) · Nature Methods · doi:10.1038/nmeth.2066 · Cited by 1,776 · see citing works
Self-citationUniRef: comprehensive and non-redundant UniProt reference clusters
Suzek, B. E., Huang, H., McGarvey, P., Mazumder, R., & Wu, C. H. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm098 · Cited by 1,613 · see citing works
Colonic bacterial composition in Parkinson's disease
Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., & Shannon, K. M. (2015) · Movement Disorders · doi:10.1002/mds.26307 · Cited by 1,281 · see citing works
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats
Holmqvist, S., Chutna, O., Bousset, L., Aldrin-Kirk, P., Li, W., Björklund, T., Wang, Z.-Y., Roybon, L., Melki, R., & Li, J.-Y. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1343-6 · Cited by 925 · see citing works
Hill‐Burns, E. M., Debelius, J. W., Morton, J. T., Wissemann, W. T., Lewis, M. R., Wallen, Z. D., Peddada, S. D., Factor, S. A., Molho, E., Zabetian, C. P., et al. (2017) · Movement Disorders · doi:10.1002/mds.26942 · Cited by 874 · see citing works
Vagotomy and subsequent risk of <scp>P</scp> arkinson's disease
Svensson, E., Horváth‐Puhó, E., Thomsen, R. W., Djurhuus, J. C., Pedersen, L., Borghammer, P., & Sørensen, H. T. (2015) · Annals of Neurology · doi:10.1002/ana.24448 · Cited by 806 · see citing works
Colonic inflammation in Parkinson's disease
Devos, D., Lebouvier, T., Lardeux, B., Biraud, M., Rouaud, T., Pouclet, H., Coron, E., Bruley des Varannes, S., Naveilhan, P., Nguyen, J.-M., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.09.007 · Cited by 627 · see citing works
Zhao, Z., Ning, J., Bao, X.-Q., Shang, M., Ma, J., Li, G., & Zhang, D. (2021) · Microbiome · doi:10.1186/s40168-021-01107-9 · Cited by 616 · see citing works
Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease
Lin, C.-H., Chen, C.-C., Chiang, H.-L., Liou, J.-M., Chang, C.-M., Lu, T.-P., Chuang, E. Y., Tai, Y.-C., Cheng, C., Lin, H.-Y., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1528-y · Cited by 469 · see citing works
Vagotomy and Parkinson disease: A Swedish register–based matched-cohort study
Liu, B., Fang, F., Pedersen, N. L., Tillander, A., Ludvigsson, J. F., Ekbom, A., Svenningsson, P., Chen, H., & Wirdefeldt, K. (2017) · Neurology · doi:10.1212/wnl.0000000000003961 · Cited by 447 · see citing works
Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT
Barichella, M., Pacchetti, C., Bolliri, C., Cassani, E., Iorio, L., Pusani, C., Pinelli, G., Privitera, G., Cesari, I., Faierman, S. A., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003127 · Cited by 390 · see citing works
Hui, K. Y., Fernandez-Hernandez, H., Hu, J., Schaffner, A., Pankratz, N., Hsu, N.-Y., Chuang, L.-S., Carmi, S., Villaverde, N., Li, X., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aai7795 · Cited by 384 · cited 1× · see citing works
“IBD and PD have been shown to share genetic risk factors, most notably in LRRK2, where the N2081 Crohn’s disease risk allele lies on the same kinase domain as a G2019S, a mutation shown to be the major genetic cause of familiar PD and a contributor to sporadic PD.(71) Further, intestinal inflammation has been shown to…”
BackgroundGut microbiota in Parkinson's disease: Temporal stability and relations to disease progression
Aho, V. T. E., Pereira, P. A. B., Voutilainen, S., Paulin, L., Pekkonen, E., Auvinen, P., & Scheperjans, F. (2019) · eBioMedicine · doi:10.1016/j.ebiom.2019.05.064 · Cited by 361 · see citing works
Gut microbiota in patients with Parkinson's disease in southern China
Lin, A., Zheng, W., He, Y., Tang, W., Wei, X., He, R., Huang, W., Su, Y., Huang, Y., Zhou, H., et al. (2018) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2018.05.007 · Cited by 253 · see citing works
Uchihara, T., & Giasson, B. I. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1485-1 · Cited by 249 · see citing works
Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study
Minato, T., Maeda, T., Fujisawa, Y., Tsuji, H., Nomoto, K., Ohno, K., & Hirayama, M. (2017) · PLOS ONE · doi:10.1371/journal.pone.0187307 · Cited by 248 · see citing works
Potential roles of gut microbiota and microbial metabolites in Parkinson’s disease
Zheng, S.-Y., Li, H.-X., Xu, R.-C., Miao, W.-T., Dai, M.-Y., Ding, S.-T., & Liu, H.-D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101347 · Cited by 101 · see citing works
Li, F., Wang, P., Chen, Z., Sui, X., Xie, X., & Zhang, J. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134297 · Cited by 97 · see citing works
Production of psychoactive metabolites by gut bacteria
Wiley, N. C., Cryan, J. F., Dinan, T. G., Ross, R. P., & Stanton, C. (2021) · Modern trends in psychiatry · doi:10.1159/000510419 · Cited by 37 · see citing works
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
The gut–brain axis in early Parkinson’s disease: from prodrome to prevention
Oliver, P. J., Civitelli, L., & Hu, M. T. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13138-5 · Cited by 42 · see citing works
“This study showed that a microbiome-based classifier had moderate accuracy in discriminating and identifying prodromal and early PD patients according to gut micro-biome profile [134].”
- Authors
- Palacios, N., Wilkinson, J., Bjornevik, K., Schwarzschild, M. A., McIver, L., Ascherio, A., & Huttenhower, C.
- Affiliations
- University of Massachusetts Lowell (US)
- Harvard University (US)
- Department of Nutrition Harvard T.H. Chan School of Public Health Boston MA
- Massachusetts General Hospital (US)
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Palacios, Natalia
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2023-07-08
- Volume
- 94
- Issue
- 3
- Pages
- 486-501
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC10538421
- OpenAlex
- W4380538639
- Cited by
- 59
- References
- 21
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 16 · 2023: 1
- FWCI
- 10.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS097723)
- National Institutes of Health (U01 CA167552, UM1 CA186107)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- Parkinson's disease, prodromal Parkinson's disease, gut microbiota, fecal metagenome, obligate anaerobes, inflammation, biomarkers, constipation, Nurses' Health Study, Health Professionals Follow-up Study
- MeSH terms
- Gastrointestinal Microbiome, Follow-Up Studies, Humans, Parkinson Disease, Case-Control Studies, Metagenomics, Prodromal Symptoms
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