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

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-2-5

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32517799

DOI Digital object identifier for electronic documents.

10.1186/s12915-020-00775-7

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

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-5

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): WikiWorks, Fcuevas3, Atrayees, Aiyshaaaa, Peace Sandy, Victoria

Subjects

Location of subjects: Luxembourg

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: 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).: raw counts

Statistical test: Linear Regression

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, sex

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, sex, constipation

Alpha Diversity

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

Richness Number of species: increased

Signature 1

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Curated date: 2022/01/22

Curator: Fcuevas3

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Source: Figure 2 and Figure 3

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

Boxplots of eight significantly changed genera in PD vs. controls (FDR < 0.05). 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 Control	Links
Akkermansia
Akkermansia muciniphila
Anaerotruncus
Anaerotruncus colihominis
Bilophila
Christensenella
Christensenella minuta
Lactobacillus
Ruminococcus bromii
Streptococcus
[Ruminococcus] torques
Acidaminococcus

Revision editor(s): Fcuevas3, Aiyshaaaa, Peace Sandy

Signature 2

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Reviewed Marked as Reviewed by Peace Sandy on 2024-2-5

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Aiyshaaaa, Peace Sandy

Source: Figure 2 and Figure 3

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

Boxplots of eight significantly changed genera in PD vs. controls (FDR < 0.05). 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: decreased abundance in Participants with typical PD

NCBI	Quality Control	Links
Roseburia intestinalis
Turicibacter
Turicibacter sanguinis

Revision editor(s): Fcuevas3, Aiyshaaaa, Peace Sandy