Gut metagenomics-derived genes as potential biomarkers of Parkinson's disease

Study information

Reviewed Marked as Reviewed by Atrayees on 2023-7-4

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32844199

DOI Digital object identifier for electronic documents.

10.1093/brain/awaa201

URI

Authors

Qian Y, Yang X, Xu S, Huang P, Li B, Du J, He Y, Su B, Xu LM, Wang L, Huang R, Chen S, Xiao Q

Journal

Brain : a journal of neurology

Year

2020

Keywords:

Parkinson’s disease, biomarker, gut microbiota, metagenome, shotgun

Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson's disease. In this study, we aimed to identify the gut microbiome associated with Parkinson's disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson's disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson's disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson's disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer's disease. We developed the first gut microbial gene catalogue associated with Parkinson's disease. Twenty-five gene markers were identified that distinguished Parkinson's disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1-96.1%). A highly accurate Parkinson's disease index, which was not influenced by disease severity or Parkinson's disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson's disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4-98.0%), but also in an independent group of 78 patients with Parkinson's disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0-95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson's disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer's disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson's disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson's disease.

Experiment 2

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Reviewed Marked as Reviewed by Atrayees on 2023-7-4

Curated date: 2022/01/18

Curator: Fcuevas3

Revision editor(s): Fcuevas3, WikiWorks, Atrayees, Peace Sandy

Differences from previous experiment shown

Subjects

Location of subjects: China

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 without any form of Parkinson's Disease

Group 1 name Corresponds to the case (exposed) group for case-control studies: Participants with idiopathic Parkinson's Disease

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: All Parkinson’s disease patients eligible for this study were diagnosed with idiopathic Parkinson’s disease according to the UK Brain Bank criteria.

Group 0 sample size Number of subjects in the control (unexposed) group: 75

Group 1 sample size Number of subjects in the case (exposed) group: 78

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Antibiotic use within 3 months prior to sample collection.

Lab analysis

Sequencing type: 16S

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).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

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, body mass index, life style, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased

Richness Number of species: increased

Signature 1

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Curated date: 2022/01/18

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Figure 2A-D.

Description: Differences in phylogenetic abundance between Parkinson’s disease patients and healthy control subjects.

Abundance in Group 1: increased abundance in Participants with idiopathic Parkinson's Disease

NCBI	Quality Control	Links
Alistipes
Enterobacter
Enterobacter cloacae
Enterocloster asparagiformis
Gordonibacter
Gordonibacter pamelaeae
Granulicatella
Granulicatella sp.
Holdemania
Holdemania filiformis
Lachnospiraceae bacterium
Lactobacillus
Ligilactobacillus salivarius
Paraprevotella clara
Streptococcus
Streptococcus anginosus
Streptococcus salivarius
Streptococcus thermophilus
Synergistota
Verrucomicrobiota
Abiotrophia
[Clostridium] leptum

Revision editor(s): Fcuevas3, Atrayees