Parkinson's disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Baldini F, Hertel J, Sandt E, Thinnes CC, Neuberger-Castillo L, Pavelka L, Betsou F, Krüger R, Thiele I
Journal
BMC biology
Year
2020
Keywords:
Computational modelling, Gut microbiome, Metabolic modelling, Parkinson’s disease, Transsulfuration pathway
BACKGROUND: Parkinson's disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson's Study (n = 147 typical PD cases, n = 162 controls). RESULTS: All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. CONCLUSION: Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.

Experiment 1


Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

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

Subjects

Location of subjects
Luxembourg
Host species Species from which microbiome was sampled (if applicable)
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
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
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
Participants with typical PD
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
PD patients were defined as typical PD, according to the inclusion criteria by the United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
Group 0 sample size Number of subjects in the control (unexposed) group
162
Group 1 sample size Number of subjects in the case (exposed) group
147
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 Months

Lab analysis

Sequencing type
16S
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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Linear Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Aiyshaaaa

Source: Figure 2 and figure 3

Description: Boxplots of significantly changed species and genera in PD vs. controls (FDR < 0.05).

Abundance in Group 1: increased abundance in Participants with typical PD

NCBI Quality ControlLinks
Akkermansia
Akkermansia muciniphila
Anaerotruncus
Anaerotruncus colihominis
Bilophila
Christensenella minuta
Lactobacillus
Ruminococcus bromii
Streptococcus
[Ruminococcus] torques
Christensenella

Revision editor(s): Fcuevas3, Aiyshaaaa

Signature 2

Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Aiyshaaaa

Source: Figure 2.

Description: Boxplots of significantly changed species and genera in PD vs. controls (FDR < 0.05).

Abundance in Group 1: decreased abundance in Participants with typical PD

NCBI Quality ControlLinks
Roseburia intestinalis
Turicibacter sanguinis
Turicibacter

Revision editor(s): Fcuevas3, Aiyshaaaa

Experiment 2


Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Excluded control persons who took dopaminergic medications (n = 5; intake for a different than anti-PD indication) and individuals who reported to have taken antibiotics in the last 6 months (controls: n = 20, PD: n = 13).

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
Not specified
Matched on Factors on which subjects have been matched on in a case-control study
Not specified
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, body mass index

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3

Source: Figure 3. Boxplots of eight significantly changed genera in PD vs. controls (FDR < 0.05).

Description: Significance levels were determined using multivariable semi-parametrical fractional regressions with the group variable (PD vs. control) as a predictor of interest, including age, gender, BMI, and technical variables (total read counts and sequencing run (batch)) as covariates. FDR, false discovery rate

Abundance in Group 1: increased abundance in Participants with typical PD

NCBI Quality ControlLinks
Christensenella
Anaerotruncus
Lactobacillus
Streptococcus
Akkermansia
Bilophila
Acidaminococcus

Revision editor(s): Fcuevas3

Signature 2

Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3

Source: Figure 3.

Description: Boxplots of eight significantly changed genera in PD vs. controls (FDR < 0.05)

Abundance in Group 1: decreased abundance in Participants with typical PD

NCBI Quality ControlLinks
Turicibacter

Revision editor(s): Fcuevas3

Experiment 3


Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

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

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Female patients with PD
Group 1 name Corresponds to the case (exposed) group for case-control studies
Male patients with PD
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female/male patients with PD according to United Kingdom Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
Group 0 sample size Number of subjects in the control (unexposed) group
57
Group 1 sample size Number of subjects in the case (exposed) group
105
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 Months

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex

Alpha Diversity

Pielou Quantifies how equal the community is numerically
increased
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3

Source: Figure 4

Description: Genus alterations in PDs in the context of basic covariates and clinical variables.

Abundance in Group 1: increased abundance in Male patients with PD

NCBI Quality ControlLinks
Paraprevotella

Revision editor(s): Fcuevas3