Dysbiosis of gut microbiota in a selected population of Parkinson's patients

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

31174953

DOI Digital object identifier for electronic documents.

10.1016/j.parkreldis.2019.06.003

URI

Authors

Pietrucci D, Cerroni R, Unida V, Farcomeni A, Pierantozzi M, Mercuri NB, Biocca S, Stefani A, Desideri A

Journal

Parkinsonism & related disorders

Year

2019

Keywords:

16S rRNA, Dysbiosis, Functional pathways, Gut microbiota, Parkinson's disease, Predictors

INTRODUCTION: In recent years the hypothesis that gut microbiota associates with Parkinson's disease (PD) has gained importance, although it has not been possible to define a specific microbiota composition as a predictive biomarker of this disease. We have investigated dysbiosis of gut microbiota in a selected population of PD patients from Central Italy, and examined the weight of specific confounders and predictors, in order to identify potential correlations with clinical phenotypes. METHODS: 152 fecal samples were collected from 80 patients and 72 healthy controls. Patients were enrolled according to tight inclusion criteria. Microbiota composition was studied through 16s ribosomal RNA gene amplicon sequencing analysis in combination with data on dietary/life habits. Age, loss of weight, and sex were recognized as confounding factors, whereas PD-status, age, Body Mass Index, "eat cereals", "gain of weigth" and "physical activity" as predictors. The presence of Lactobacillaceae, Enterobacteriaceae and Enterococcaceae families was significantly higher in feces from PD patients compared to healthy controls, while Lachnospiraceae were significantly reduced. Lower levels of Lachnospiraceae and higher levels of Enterobacteriaceae families also correlated with increased disease severity and motor impairment (Hoehn & Yahr stage, MDS-UPDRS Part III). Predictive metagenomics indicated a significant variation of genes involved in the metabolism of short chain fatty acids and amino acids, and in lipopolysaccharide biosynthesis. CONCLUSIONS: PD showed a distinctive microbiota composition. Functional predictions suggest changes in pathways favoring a pro-inflammatory environment in the gastrointestinal tract, and a reduction in the biosynthesis of amino acids acting as precursors of physiological transmitters.

Experiment 1

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Curated date: 2024/03/08

Curator: Mojisayo Awolesi

Revision editor(s): Mojisayo Awolesi, Fiddyhamma, Scholastica

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

Healthy controls (HC)

Group 1 name Corresponds to the case (exposed) group for case-control studies

Parkinson's disease (PD)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients with severe and active Parkinson disease. Recruited patients had a diagnosis of idiopathic PD according to the UK Parkinson's Disease Society Brain Bank criteria with a disease duration (measured as the time following the first diagnosis) longer than 6 months

Group 0 sample size Number of subjects in the control (unexposed) group

72

Group 1 sample size Number of subjects in the case (exposed) group

80

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

4 weeks

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

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

age, sex, Confounders controlled for: "loss of weight" 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.loss of weight

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

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

Revision editor(s): Scholastica, Fiddyhamma, Mojisayo Awolesi, Welile

Source: Supplementary Table S7A

Description: Significantly abundant bacterial families and genera in Parkinson's disease versus healthy controls (HC) detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test)

Abundance in Group 1: increased abundance in Parkinson's disease (PD)

NCBI	Quality Control	Links
Citrobacter
Enterobacteriaceae
Enterococcaceae
Enterococcus
Klebsiella
Lactobacillaceae
Lactococcus
Salmonella
Shigella
unclassified Enterobacteriaceae

Revision editor(s): Scholastica, Fiddyhamma, Mojisayo Awolesi, Welile

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

Revision editor(s): Scholastica, Fiddyhamma, Mojisayo Awolesi, Welile

Source: Supplementary Table S7A

Description: Significantly abundant bacterial families and genera in Parkinson's disease versus healthy controls (HC) detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test)

Abundance in Group 1: decreased abundance in Parkinson's disease (PD)

NCBI	Quality Control	Links
Lachnospiraceae
Roseburia

Revision editor(s): Scholastica, Fiddyhamma, Mojisayo Awolesi, Welile

Experiment 2

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

Revision editor(s): Mojisayo Awolesi, Fiddyhamma, Scholastica

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Parkinson's disease (excluding iCOMT users)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients with Parkinson's disease (PD) excluding eight patients taking catechol-O-methyl transferase (COMT) inhibitors

Group 1 sample size Number of subjects in the case (exposed) group

72

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2024/04/12

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Scholastica

Source: Supplementary Table S7B

Description: Significantly abundant bacterial families and genera in Parkinson's disease (excluding iCOMT users) versus healthy controls detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test)

Abundance in Group 1: increased abundance in Parkinson's disease (excluding iCOMT users)

NCBI	Quality Control	Links
Enterobacteriaceae
Enterococcaceae
Klebsiella
Lactobacillaceae
Lactobacillus
unclassified Enterobacteriaceae

Revision editor(s): Fiddyhamma, Scholastica

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Curated date: 2024/04/12

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Scholastica

Source: Supplementary Table S7B

Description: Significantly abundant bacterial families and genera in Parkinson's disease (excluding iCOMT users) versus healthy controls detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test)

Abundance in Group 1: decreased abundance in Parkinson's disease (excluding iCOMT users)

NCBI	Quality Control	Links
Lachnospiraceae

Revision editor(s): Fiddyhamma, Scholastica