Clinical Phenotypes of Parkinson's Disease Associate with Distinct Gut Microbiota and Metabolome Enterotypes

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Vascellari S, Melis M, Palmas V, Pisanu S, Serra A, Perra D, Santoru ML, Oppo V, Cusano R, Uva P, Atzori L, Morelli M, Cossu G, Manzin A
Journal
Biomolecules
Year
2021
Keywords:
clinical phenotype, gut microbiota, metabolome, parkinson’s disease
Parkinson's disease (PD) is a clinically heterogenic disorder characterized by distinct clinical entities. Most studies on motor deficits dichotomize PD into tremor dominant (TD) or non-tremor dominant (non-TD) with akinetic-rigid features (AR). Different pathophysiological mechanisms may affect the onset of motor manifestations. Recent studies have suggested that gut microbes may be involved in PD pathogenesis. The aim of this study was to investigate the gut microbiota and metabolome composition in PD patients in relation to TD and non-TD phenotypes. In order to address this issue, gut microbiota and the metabolome structure of PD patients were determined from faecal samples using 16S next generation sequencing and gas chromatography-mass spectrometry approaches. The results showed a reduction in the relative abundance of Lachnospiraceae, Blautia, Coprococcus, Lachnospira, and an increase in Enterobacteriaceae, Escherichia and Serratia linked to non-TD subtypes. Moreover, the levels of important molecules (i.e., nicotinic acid, cadaverine, glucuronic acid) were altered in relation to the severity of phenotype. We hypothesize that the microbiota/metabolome enterotypes associated to non-TD subtypes may favor the development of gut inflammatory environment and gastrointestinal dysfunctions and therefore a more severe α-synucleinopathy. This study adds important information to PD pathogenesis and emphasizes the potential pathophysiological link between gut microbiota/metabolites and PD motor subtypes.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/17

Curator: Junie

Revision editor(s): Junie, Peace Sandy

Subjects

Location of subjects
Italy
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
Parkinson's disease patients with Tremor Dominant - TD
Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's disease patients with Akinetic Rigid - AR
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A phenotype category based on motor signs
Group 0 sample size Number of subjects in the control (unexposed) group
19
Group 1 sample size Number of subjects in the case (exposed) group
23
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months prior to enrollment

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
LEfSe
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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, smoking status, Confounders controlled for: "coffee consumption" 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.coffee consumption, Confounders controlled for: "pharmacological treatment" 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.pharmacological treatment

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
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/18

Curator: Junie

Revision editor(s): Junie, Peace Sandy

Source: Figure 3a

Description: Linear discriminant analysis effect size (LEfSE) analysis: The bar plots represent the significantly different taxa among PD patients with distinct motor phenotypes, based on effect size (Linear discriminant analysis (LDA) score (log 10) > 2). (a) Positive LDA score (green) highlights the enriched taxa in PD patients with Tremor Dominant (TD) and negative LDA score (red) shows the enriched taxa in PD patients with Akinetic Rigid (AR);

Abundance in Group 1: increased abundance in Parkinson's disease patients with Akinetic Rigid - AR

NCBI Quality ControlLinks
Sedimentibacter
Serratia
Escherichia
Enterobacteriaceae

Revision editor(s): Junie, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/18

Curator: Junie

Revision editor(s): Junie, Peace Sandy

Source: Figure 3a

Description: Linear discriminant analysis effect size (LEfSE) analysis: The bar plots represent the significantly different taxa among PD patients with distinct motor phenotypes, based on effect size (Linear discriminant analysis (LDA) score (log 10) > 2). (a) Positive LDA score (green) highlights the enriched taxa in PD patients with Tremor Dominant (TD) and negative LDA score (red) shows the enriched taxa in PD patients with Akinetic Rigid (AR);

Abundance in Group 1: decreased abundance in Parkinson's disease patients with Akinetic Rigid - AR

NCBI Quality ControlLinks
Bacillota
Lachnospiraceae
Clostridiaceae
Faecalibacterium
Blautia
Coprococcus
Lachnospira
Tindallia
Gemellaceae
Gemella
Brevibacteriaceae
Brevibacterium

Revision editor(s): Junie, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Parkinson's disease patients with Tremor Dominant - TD
Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's disease patients with Diskinetic - D
Group 1 sample size Number of subjects in the case (exposed) group
14

Lab analysis

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
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3B

Description: Linear discriminant analysis effect size (LEfSE) analysis: The bar plots represent the significantly different taxa among PD patients with distinct motor phenotypes, based on effect size(Linear discriminant analysis (LDA) score (log 10) > 2). (b) Positive LDA score (green) highlights enriched taxa in PD patients with Tremor Dominant (TD) and negative LDA score (red) shows enriched taxa in PD with Dyskinetic (D)

Abundance in Group 1: increased abundance in Parkinson's disease patients with Diskinetic - D

NCBI Quality ControlLinks
Serratia
Lactobacillus
Lactobacillaceae
Escherichia
Enterobacteriaceae

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3B

Description: Linear discriminant analysis effect size (LEfSE) analysis: The bar plots represent the significantly different taxa among PD patients with distinct motor phenotypes, based on effect size(Linear discriminant analysis (LDA) score (log 10) > 2). (b) Positive LDA score (green) highlights enriched taxa in PD patients with Tremor Dominant (TD) and negative LDA score (red) shows enriched taxa in PD with Dyskinetic (D)

Abundance in Group 1: decreased abundance in Parkinson's disease patients with Diskinetic - D

NCBI Quality ControlLinks
Bacillota
Oscillospiraceae
Clostridiaceae
Lachnospiraceae
Faecalibacterium
Blautia
Coprococcus
Lachnospira
Peptococcaceae
Sedimentibacter
Tindallia
Eubacteriaceae
Acetanaerobacterium
Brevibacterium
Brevibacteriaceae
Gemellaceae
Gemella

Revision editor(s): Peace Sandy

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Parkinson's disease patients with Diskinetic - D
Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's disease patients with Akinetic Rigid - AR
Group 0 sample size Number of subjects in the control (unexposed) group
14
Group 1 sample size Number of subjects in the case (exposed) group
23

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, body mass index, Confounders controlled for: "coffe consumption" 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.coffe consumption, smoking status, Confounders controlled for: "pharmalogical treatment" 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.pharmalogical treatment

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
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-3-19

Curated date: 2024/03/19

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3C

Description: Linear discriminant analysis effect size (LEfSE) analysis: The bar plots represent the significantly different taxa among PD patients with distinct motor phenotypes, based on effect size (Linear discriminant analysis (LDA) score (log 10) > 2). (c) Positive LDA score (green) highlights enriched taxa in PD patients with Dyskinetic

Abundance in Group 1: decreased abundance in Parkinson's disease patients with Akinetic Rigid - AR

NCBI Quality ControlLinks
Lactobacillus
Lactobacillaceae

Revision editor(s): Peace Sandy