Metagenomics of the Gut Microbiome in Parkinson's Disease: Prodromal Changes

Study information

Reviewed Marked as Reviewed by Svetlana up on 2025-2-27

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

37314861

DOI Digital object identifier for electronic documents.

10.1002/ana.26719

URI

Authors

Palacios N, Wilkinson J, Bjornevik K, Schwarzschild MA, McIver L, Ascherio A, Huttenhower C

Journal

Annals of neurology

Year

2023

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.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-2-27

Curated date: 2025/02/25

Curator: KateRasheed

Revision editor(s): KateRasheed

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Parkinson's disease IDIOPATHIC PARKINSON DIS,Idiopathic Parkinson Disease,Idiopathic Parkinson's Disease,IDIOPATHIC PARKINSONS DIS,Idiopathic PD,LEWY BODY PARKINSON DIS,Lewy Body Parkinson Disease,Lewy Body Parkinson's Disease,Paralysis agitans,paralysis agitans,PARKINSON DIS,PARKINSON DIS IDIOPATHIC,Parkinson disease,Parkinson Disease, Idiopathic,Parkinson syndrome,Parkinson's,Parkinson's disease,Parkinson's disease (disorder),Parkinson's disease NOS,Parkinson's disease NOS (disorder),Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinson's syndrome,Parkinsonian disorder,Parkinsonism, Primary,Parkinsons,PARKINSONS DIS,PARKINSONS DIS IDIOPATHIC,PARKINSONS DIS LEWY BODY,Parkinsons disease,Primary Parkinsonism,parkinson's disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Recently diagnosed Parkinson's disease patients (PD)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Recently diagnosed PD refers to patients with onset Parkinson's disease (the second most common neurodegenerative disease globally, impacting approximately 1% of the population 65 years and older).

Group 0 sample size Number of subjects in the control (unexposed) group: 131

Group 1 sample size Number of subjects in the case (exposed) group: 75

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: arcsine square-root

Statistical test: MaAsLin2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.20

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Matched on Factors on which subjects have been matched on in a case-control study: age

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, Confounders controlled for: "sequencing batch" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.sequencing batch, Confounders controlled for: "pack-years of smoking" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.pack-years of smoking, Confounders controlled for: "Mediterranean Dietary Pattern (MED diet) adherence" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Mediterranean Dietary Pattern (MED diet) adherence

Signature 1

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Source: In text of the "Individual Species and Functions Are Similarly Associated with Recently Onset PD and PPS" section and PD_Dataverse_taxa

Description: Significantly differential abundance of taxa identified via feature-wise analyses (MaAsLin 2)

Abundance in Group 1: increased abundance in Recently diagnosed Parkinson's disease patients (PD)

NCBI	Quality Control	Links
Bifidobacterium longum
Ruthenibacterium lactatiformans
Mediterraneibacter gnavus
Streptococcus salivarius
[Clostridium] leptum
Bifidobacterium dentium
Eisenbergiella tayi
Gordonibacter pamelaeae

Revision editor(s): KateRasheed

Signature 2

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Source: In text of the "Individual Species and Functions Are Similarly Associated with Recently Onset PD and PPS" section and PD_Dataverse_taxa

Description: Significantly differential abundance of taxa identified via feature-wise analyses (MaAsLin 2)

Abundance in Group 1: decreased abundance in Recently diagnosed Parkinson's disease patients (PD)

NCBI	Quality Control	Links
Eubacterium ramulus
Lawsonibacter asaccharolyticus
Bacteroides xylanisolvens
Roseburia intestinalis
Roseburia faecis
Agathobacter rectalis
[Eubacterium] siraeum
Faecalibacterium prausnitzii
Oscillibacter sp. 57_20

Revision editor(s): KateRasheed

Experiment 3

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Curated date: 2025/02/25

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Prodromal (Premotor) Parkinson's syndrome (PPS)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Prodromal (Premotor) Parkinson's syndrome (PPS) refers to patients that had constipation, pRBD, and substantial loss of smell.

Group 1 sample size Number of subjects in the case (exposed) group: 101

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, Confounders controlled for: "sequencing batch" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.sequencing batch, Confounders controlled for: "pack-years of smoking" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.pack-years of smoking, Confounders controlled for: "MED diet adherence" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.MED diet adherence