Integrated Microbiome and Host Transcriptome Profiles Link Parkinson's Disease to Blautia Genus: Evidence From Feces, Blood, and Brain

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Reviewed Marked as Reviewed by Svetlana up on 2024-12-24
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Guo X, Tang P, Hou C, Chong L, Zhang X, Liu P, Chen L, Liu Y, Zhang L, Li R
Journal
Frontiers in microbiology
Year
2022
Keywords:
16S, Blautia, Parkinson’s disease, feces, microbiome
A link between the gut microbiome and Parkinson's disease (PD) has been intensively studied, and more than 100 differential genera were identified across the studies. However, the predominant genera contributing to PD remain poorly understood. Inspired by recent advances showing microbiota distribution in the blood and brain, we, here, comprehensively investigated currently available fecal microbiome data (1,914 samples) to identify significantly altered genera, which were further validated by comparison to the results from microbiome analysis of blood (85 samples) and brain (268 samples). Our data showed that the composition of fecal microbiota was different from that of blood and brain. We found that Blautia was the unique genus consistently depleted across feces, blood, and brain samples of PD patients (P < 0.05), despite using rigorous criteria to remove contaminants. Moreover, enrichment analyses revealed that host genes correlated with Blautia genus abundance were mainly involved in mitochondrial function and energy metabolism, and mapped to neurodegenerative diseases (NDDs) and metabolic diseases. A random forest classifier constructed with fecal microbiota data demonstrated that Blautia genus was an important feature contributing to discriminating PD patients from controls [receiver operating characteristic (ROC)-area under curve (AUC) = 0.704, precision-recall curve (PRC)-AUC = 0.787]. Through the integration of microbiome and transcriptome, our study depicted microbial profiles in the feces, blood, and brain of PD patients, and identified Blautia genus as a potential genus linked to PD. Further studies are greatly encouraged to determine the role of Blautia genus in the pathogenesis of PD.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Subjects

Location of subjects
China
Denmark
Finland
Germany
Italy
Japan
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
Controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
PD patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Parkinson's disease
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
10

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, Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
DESeq2
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)?
No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Source: Supplementary Table 4

Description: Significantly changed fecal genera classified by Greengenes between PD patients and controls

Abundance in Group 1: increased abundance in PD patients

NCBI Quality ControlLinks
Acidaminococcus
Anaerofustis
Anaerotruncus
Campylobacter
Citrobacter
Coprobacillus
Dehalobacterium
Dorea
Eubacterium
Finegoldia
Halomonas
Methanobrevibacter
Methanomassiliicoccus
Peptoniphilus
Pseudoramibacter alactolyticus
Ruminococcus
Sporobacterium sp. WAL 1855D
Synergistes
Turicibacter
Varibaculum
cc_115cc_115
1-681-68
ph2ph2

Revision editor(s): Leenaa, Fiddyhamma

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Source: Supplementary Table 4

Description: Significantly changed fecal genera classified by Greengenes between PD patients and controls

Abundance in Group 1: decreased abundance in PD patients

NCBI Quality ControlLinks
Bacteroides
Blautia
Faecalibacterium
Lachnospira
Phascolarctobacterium
Prevotella
Roseburia
Sutterella
rc4-4rc4-4

Revision editor(s): Leenaa, Fiddyhamma

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Differences from previous experiment shown

Subjects

Location of subjects
China
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Blood Portion of blood,Vertebrate blood,Whole blood,Blood,blood
Group 0 sample size Number of subjects in the control (unexposed) group
1
Group 1 sample size Number of subjects in the case (exposed) group
1

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa

Source: Supplementary Table 6

Description: Significantly changed genera in the blood samples between PD patients and controls

Abundance in Group 1: decreased abundance in PD patients

NCBI Quality ControlLinks
Blautia
Dorea
Meiothermus
Nesterenkonia

Revision editor(s): Leenaa

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Differences from previous experiment shown

Subjects

Location of subjects
Israel
Netherlands
United States of America
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Brain Encephalon,Suprasegmental levels of nervous system,Suprasegmental structures,Synganglion,The brain,Brain,brain
Group 0 sample size Number of subjects in the control (unexposed) group
5
Group 1 sample size Number of subjects in the case (exposed) group
5

Lab analysis

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

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Source: Supplementary Table 7

Description: Significantly changed genera in the brain between PD patients and controls

Abundance in Group 1: increased abundance in PD patients

NCBI Quality ControlLinks
Cronobacter
Nocardioides
Planctomyces
Rathayibacter
Syntrophobacter

Revision editor(s): Leenaa, Fiddyhamma

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/03/27

Curator: Leenaa

Revision editor(s): Leenaa, Fiddyhamma

Source: Supplementary table 7

Description: Significantly changed genera in the brain between PD patients and controls

Abundance in Group 1: decreased abundance in PD patients

NCBI Quality ControlLinks
Bacteroides
Blautia
Elizabethkingia
Erythrobacter
Finegoldia
Halomonas
Pseudonocardia
Thermoanaerobacterium

Revision editor(s): Leenaa, Fiddyhamma

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/12/20

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Location of subjects
China
Denmark
Finland
Germany
Italy
Japan
United States of America
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
Group 0 sample size Number of subjects in the control (unexposed) group
16
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina, Roche454

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/12/20

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Supplementary table 5

Description: Significantly changed fecal genera classified by SILVA between PD patients and controls

Abundance in Group 1: increased abundance in PD patients

NCBI Quality ControlLinks
Methanobrevibacter
Acidaminococcus
Campylobacter
Citrobacter
Proteus
Varibaculum
Gallicola
Finegoldia
Peptoniphilus
Mogibacterium
Turicibacter
Pediococcus
Anaerofustis
Anaerotruncus

Revision editor(s): Fiddyhamma

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-24

Curated date: 2024/12/20

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Supplementary table 5

Description: Significantly changed fecal genera classified by SILVA between PD patients and controls

Abundance in Group 1: decreased abundance in PD patients

NCBI Quality ControlLinks
Phascolarctobacterium
Sutterella
Bacteroides
Faecalibacterium
Anaerostipes
Lachnospira
Roseburia
Blautia
Dorea

Revision editor(s): Fiddyhamma