Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson's disease patients

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

28449715

DOI Digital object identifier for electronic documents.

10.1186/s13073-017-0428-y

URI

Authors

Bedarf JR, Hildebrand F, Coelho LP, Sunagawa S, Bahram M, Goeser F, Bork P, Wüllner U

Journal

Genome medicine

Year

2017

Keywords:

Archaea, Bacteria, Enteric nervous system, Gut-brain axis, Microbiome, Parkinson, Viruses

BACKGROUND: Parkinson's disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker. METHODS: We performed metagenomic shotgun analyses and compared the fecal microbiomes of 31 early stage, L-DOPA-naïve PD patients to 28 age-matched controls. RESULTS: We found increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) were markedly lowered in PD samples. The observed differences could reliably separate PD from control with a ROC-AUC of 0.84. Functional analyses of the metagenomes revealed differences in microbiota metabolism in PD involving the ẞ-glucuronate and tryptophan metabolism. While the abundances of prophages and plasmids did not differ between PD and controls, total virus abundance was decreased in PD participants. Based on our analyses, the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in summary relates to 90% of PD patients) had no overall influence on taxa abundance or microbial functions. CONCLUSIONS: Our data revealed differences of colonic microbiota and of microbiota metabolism between PD patients and controls at an unprecedented detail not achievable through 16S sequencing. The findings point to a yet unappreciated aspect of PD, possibly involving the intestinal barrier function and immune function in PD patients. The influence of the parkinsonian medication should be further investigated in the future in larger cohorts.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

Curated date: 2021/11/14

Curator: Fcuevas3

Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Fcuevas3, Atrayees, Aiyshaaaa

Subjects

Location of subjects: Germany

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 men without Parkinsons's Disease.

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Only early stage PD men who were naïve to L-DOPA therapy as diagnosed according to the UK Brain Bank criteria.

Group 0 sample size Number of subjects in the control (unexposed) group: 28

Group 1 sample size Number of subjects in the case (exposed) group: 31

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): The use of antibiotics in the past three months in principle was an exclusion criterion. However, we included three PD patients and three controls despite the intake of antibiotics for one to three days in a period of 28–34 days prior to feces sampling as the omission of those cases from the analyses did not change any result

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: Kruskall-Wallis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1

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, sex

Alpha Diversity

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

Richness Number of species: unchanged

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

Curated date: 2021/11/14

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Claregrieve1

Source: Figure 1C

Description: Differential microbial abundance between PD participants and controls

Abundance in Group 1: increased abundance in Men with Parkinson's Disease.

NCBI	Quality Control	Links
Akkermansia muciniphila
Alistipes shahii
Lacrimispora saccharolytica
unclassified Bacillota
unclassified Bacteria
Eubacterium sp.
unclassified Clostridia

Revision editor(s): Fcuevas3, Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

Curated date: 2021/11/14

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Claregrieve1

Source: Figure 1C

Description: Differential microbial abundance between PD participants and controls

Abundance in Group 1: decreased abundance in Men with Parkinson's Disease.

NCBI	Quality Control	Links
Holdemanella biformis
Segatella copri

Revision editor(s): Fcuevas3, Claregrieve1