Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, Peddada SD, Factor SA, Molho E, Zabetian CP, Knight R, Payami H
Journal
Movement disorders : official journal of the Movement Disorder Society
Year
2017
Keywords:
Parkinson's disease, confounding, functional pathways, gut microbiome, medications
BACKGROUND: There is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD. OBJECTIVE: The objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. METHODS: A total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. RESULTS: Independent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation. CONCLUSION: PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society.

Experiment 1


Needs review

Curated date: 2024/04/17

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Subjects

Location of subjects
United States of America
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
Controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's Disease Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with Parkinson's disease by a movement disorder specialist according to the modified UK Brain Bank criteria.
Group 0 sample size Number of subjects in the control (unexposed) group
130
Group 1 sample size Number of subjects in the case (exposed) group
197

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
ANCOM
Kruskall-Wallis
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, diet, geographic area, sex, Confounders controlled for: "transit-time" 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.transit-time


Signature 1

Needs review

Curated date: 2024/04/17

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 1 and Table 2

Description: Taxa identified by ANCOM and Kruskal-Wallis test as having significantly different abundance in cases and controls.

Abundance in Group 1: increased abundance in Parkinson's Disease Patients

NCBI Quality ControlLinks
Bifidobacterium
Bifidobacterium sp.
Parabacteroides
Prevotella
unclassified Oscillospiraceae
Lactobacillus
unclassified Christensenellaceae
Akkermansia
Bifidobacteriaceae
Lactobacillaceae
Tissierellaceae
Christensenellaceae
Verrucomicrobiaceae

Revision editor(s): Aleru Divine

Signature 2

Needs review

Curated date: 2024/04/18

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 1 and Table 2

Description: Taxa identified by ANCOM and Kruskal-Wallis test as having significantly different abundance in cases and controls.

Abundance in Group 1: decreased abundance in Parkinson's Disease Patients

NCBI Quality ControlLinks
Blautia
Blautia sp.
Coprococcus
Faecalibacterium
Lachnospiraceae
Pasteurellaceae
Roseburia
unclassified Lachnospiraceae

Revision editor(s): Aleru Divine

Experiment 2


Needs review

Curated date: 2024/04/17

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with Parkinson's disease who were not on catechol-o-methyl-transferase (COMT) inhibitors or anticholinergic drugs (AC).
Group 1 sample size Number of subjects in the case (exposed) group
141

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/04/18

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 1 and Table 2

Description: Taxa identified by ANCOM and Kruskal-Wallis test as having significantly different abundance in cases and controls.

Abundance in Group 1: increased abundance in Parkinson's Disease Patients

NCBI Quality ControlLinks
Bifidobacterium
Bifidobacterium sp.
Parabacteroides
Prevotella
Lactobacillus
unclassified Oscillospiraceae
unclassified Christensenellaceae
Akkermansia
Bifidobacteriaceae
Lactobacillaceae
Tissierellaceae
Christensenellaceae
Verrucomicrobiaceae

Revision editor(s): Aleru Divine

Signature 2

Needs review

Curated date: 2024/04/18

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 1 and Table 2

Description: Taxa identified by ANCOM and Kruskal-Wallis test as having significantly different abundance in cases and controls.

Abundance in Group 1: decreased abundance in Parkinson's Disease Patients

NCBI Quality ControlLinks
Blautia
Blautia sp.
Coprococcus
Faecalibacterium
Lachnospiraceae
Pasteurellaceae
Roseburia
unclassified Lachnospiraceae

Revision editor(s): Aleru Divine