Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson's disease

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Rosario D, Bidkhori G, Lee S, Bedarf J, Hildebrand F, Le Chatelier E, Uhlen M, Ehrlich SD, Proctor G, Wüllner U, Mardinoglu A, Shoaie S
Journal
Cell reports
Year
2021
Keywords:
Parkinson’s disease, gut microbiota, gut-brain axis, metabolic modeling, metagenomics
Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement of the GI tract and enteric nervous system highlights the need for better understanding of the role of gut microbiota in GI complications in PD. Here, we investigate the gut microbiome of patients with PD using metagenomics and serum metabolomics. We integrate these data using metabolic modeling and construct an integrative correlation network giving insight into key microbial species linked with disease severity, GI dysfunction, and age of patients with PD. Functional analysis reveals an increased microbial capability to degrade mucin and host glycans in PD. Personalized community-level metabolic modeling reveals the microbial contribution to folate deficiency and hyperhomocysteinemia observed in patients with PD. The metabolic modeling approach could be applied to uncover gut microbial metabolic contributions to PD pathophysiology.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/09

Curator: Raihanat

Revision editor(s): Raihanat, Peace Sandy

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 controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with Parkinson's Disease
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient with Early-stage L-DOPA-Naive Parkinson's Disease
Group 0 sample size Number of subjects in the control (unexposed) group
11
Group 1 sample size Number of subjects in the case (exposed) group
26
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
N/A

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).
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


Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/09

Curator: Raihanat

Revision editor(s): Raihanat, Peace Sandy

Source: Figure S1

Description: Representation of the most significant (FDR < 0.01) classified taxonomic alterations between Parkinson’s disease (PD) and controls.

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

NCBI Quality ControlLinks
Akkermansia
Akkermansiaceae
Bacillota
Bacteroides
Christensenellaceae bacterium
Euryarchaeota
Methanobacteriaceae
Methanobrevibacter
Ruminiclostridium
Ruthenibacterium
Verrucomicrobiae
Intestinimonas
Christensenella
Christensenellaceae

Revision editor(s): Raihanat, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/12

Curator: Raihanat

Revision editor(s): Raihanat

Source: Figure S1

Description: Representation of the most significant (FDR < 0.01) classified taxonomic alterations between Parkinson’s disease (PD) and controls.

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

NCBI Quality ControlLinks
Bacteroidota
Faecalibacterium
Fusobacteriaceae
Haemophilus
Holdemanella
Lachnoclostridium
Lachnospiraceae
Muribaculaceae
Roseburia
Slackia
Sutterella
Veillonella
Fusobacteriia
Erysipelotrichaceae
Pasteurellaceae
Sutterellaceae

Revision editor(s): Raihanat

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/15

Curator: Raihanat

Revision editor(s): Raihanat, Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Diseased Controls
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Early-stage L-DOPA-Naive Parkinson's Disease
Group 0 sample size Number of subjects in the control (unexposed) group
14

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/16

Curator: Raihanat

Revision editor(s): Raihanat, Peace Sandy

Source: Figure S1

Description: Representation of the most significant (FDR < 0.01) classified taxonomic alterations between Parkinson’s disease (PD) and Diseased Controls(DC)

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

NCBI Quality ControlLinks
Adlercreutzia
Akkermansia
Akkermansiaceae
Alistipes
Anaerostipes
Azospirillum
Clostridiaceae
Clostridium
Fusicatenibacter
Monoglobus
Peptostreptococcaceae
Rhodospirillaceae
Rickenellaceae
Romboutsia
Thomasclavelia ramosa
Verrucomicrobiae
Victivallaceae
Victivallis
uncultured Ruminiclostridium sp.
Merdimonas

Revision editor(s): Raihanat, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-4-9

Curated date: 2024/03/16

Curator: Raihanat

Revision editor(s): Raihanat, Peace Sandy

Source: Figure S1

Description: Representation of the most significant (FDR < 0.01) classified taxonomic alterations between Parkinson’s disease (PD) and Diseased Controls (DC)

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

NCBI Quality ControlLinks
Actinomyces
Actinomycetaceae
Anaeroglobus geminatus
Atopobiaceae
Atopobium
Bacteroidota
Brachyspira
Brachyspiraceae
Butyricimonas
Catenibacterium
Clostridiaceae
Collinsella
Coprobacter
Coriobacteriaceae
Erysipelotrichaceae
Fournierella
Haemophilus
Holdemanella
Lactobacillaceae
Lactobacillus
Olsenella
Paraprevotella
Pasteurellaceae
Prevotella
Spirochaeta
Streptococcaceae
Streptococcus
Succinatimonas
Succinivibrionaceae
Tyzzerella
Muribaculaceae

Revision editor(s): Raihanat, Peace Sandy