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

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


Needs review

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

Revision editor(s): Mojisayo Awolesi, Fiddyhamma

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

Needs review

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

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

Source: Table1A, Figure 1, Suppl table S7A and text

Description: PD cases vs HC, both bacterial Families and genera with a significative p-values detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test) are reported.

Abundance in Group 1: increased abundance in Parkinson Disease

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

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

Signature 2

Needs review

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

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

Source: Table 1A, Figure 1, Suppl table S7A and text

Description: PD cases vs HC, both bacterial Families and genera with a significative p-values detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test) are reported.

Abundance in Group 1: decreased abundance in Parkinson Disease

NCBI Quality ControlLinks
Lachnospiraceae
Roseburia

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

Experiment 2


Needs review

Curated date: 2024/03/08

Curator: Mojisayo Awolesi

Revision editor(s): Mojisayo Awolesi, Fiddyhamma

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson Disease (excluding patients taking iCOMT)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with severe and active Parkinson’s disease taking catechol-O-methyl transferase (COMT) inhibitors are excluded from the analysis, since assumption of COMT inhibitors affects the microbiota composition
Group 1 sample size Number of subjects in the case (exposed) group
72

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/04/12

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Table 1B, Fig 1, Suppl table S7B and text

Description: PD (excluding patients taking iCOMT) cases vs HC, both bacterial Families and genera with a significative p-values detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test) are reported.

Abundance in Group 1: increased abundance in Parkinson Disease (excluding patients taking iCOMT)

NCBI Quality ControlLinks
Enterobacteriaceae
Lactobacillaceae
Enterococcaceae
Klebsiella
Lactobacillus
unclassified Enterobacteriaceae

Revision editor(s): Fiddyhamma

Signature 2

Needs review

Curated date: 2024/04/12

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Table 1B, Fig 1, Suppl table S7B and text

Description: PD (excluding patients taking iCOMT) cases vs HC, both bacterial Families and genera with a significative p-values detected by two methods (Generalized Linear Models and Wilcoxon-Mann-Withney test) are reported.

Abundance in Group 1: decreased abundance in Parkinson Disease (excluding patients taking iCOMT)

NCBI Quality ControlLinks
Lachnospiraceae

Revision editor(s): Fiddyhamma