Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32566740

DOI Digital object identifier for electronic documents.

10.1038/s41531-020-0112-6

URI

Authors

Wallen ZD, Appah M, Dean MN, Sesler CL, Factor SA, Molho E, Zabetian CP, Standaert DG, Payami H

Journal

NPJ Parkinson's disease

Year

2020

Keywords:

Genomics, Parkinson's disease

In Parkinson's disease (PD), gastrointestinal features are common and often precede the motor signs. Braak and colleagues proposed that PD may start in the gut, triggered by a pathogen, and spread to the brain. Numerous studies have examined the gut microbiome in PD; all found it to be altered, but found inconsistent results on associated microorganisms. Studies to date have been small (N = 20 to 306) and are difficult to compare or combine due to varied methodology. We conducted a microbiome-wide association study (MWAS) with two large datasets for internal replication (N = 333 and 507). We used uniform methodology when possible, interrogated confounders, and applied two statistical tests for concordance, followed by correlation network analysis to infer interactions. Fifteen genera were associated with PD at a microbiome-wide significance level, in both datasets, with both methods, with or without covariate adjustment. The associations were not independent, rather they represented three clusters of co-occurring microorganisms. Cluster 1 was composed of opportunistic pathogens and all were elevated in PD. Cluster 2 was short-chain fatty acid (SCFA)-producing bacteria and all were reduced in PD. Cluster 3 was carbohydrate-metabolizing probiotics and were elevated in PD. Depletion of anti-inflammatory SCFA-producing bacteria and elevated levels of probiotics are confirmatory. Overabundance of opportunistic pathogens is an original finding and their identity provides a lead to experimentally test their role in PD.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): WikiWorks, Claregrieve1, Fcuevas3, Peace Sandy, Fiddyhamma

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: Healthy controls free of neurological disease

Group 1 name Corresponds to the case (exposed) group for case-control studies: Participants with Parkinson's Disease

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Dataset 1. Participants with Parkinson's Disease, diagnosed by a movement disorder specialist using UK Brain Bank criteria.

Group 0 sample size Number of subjects in the control (unexposed) group: 136

Group 1 sample size Number of subjects in the case (exposed) group: 212

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: 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: 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, alcohol drinking, body mass index, sex, constipation, Confounders controlled for: "loss of 10 lbs in past year" 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 10 lbs in past year, Confounders controlled for: "gastrointestinal discomfort on day of stool collection" 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.gastrointestinal discomfort on day of stool collection, Confounders controlled for: "fruits or vegetables daily" 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.fruits or vegetables daily, Confounders controlled for: "stool sample travel 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.stool sample travel time, Confounders controlled for: "stool sample travel 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.stool sample travel time, geographic area

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Claregrieve1

Source: Figure 2.

Description: Differential abundances of microbial taxa between healthy controls and PD patients

Abundance in Group 1: increased abundance in Participants with Parkinson's Disease

NCBI	Quality Control	Links
Bifidobacterium
Corynebacterium
Lactobacillus
Porphyromonas
Prevotella

Revision editor(s): Fcuevas3, Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Claregrieve1

Source: Figure 2.

Description: Differential abundances of microbial taxa between healthy controls and PD patients

Abundance in Group 1: decreased abundance in Participants with Parkinson's Disease

NCBI	Quality Control	Links
Agathobacter
Blautia
Butyricicoccus
Faecalibacterium
Fusicatenibacter
Lachnospira
Lachnospiraceae
Oscillospira
Roseburia

Revision editor(s): Fcuevas3, Claregrieve1

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Claregrieve1, WikiWorks, Fiddyhamma

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy control free of neurological disease.

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Dataset 2. PD was diagnosed by a movement disorder specialist using UK Brain Bank criteria

Group 0 sample size Number of subjects in the control (unexposed) group: 184

Group 1 sample size Number of subjects in the case (exposed) group: 323

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified

Statistical test: Mann-Whitney (Wilcoxon)

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, sex, Confounders controlled for: "loss of 10lbs in the past year" 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 10lbs in the past year, Confounders controlled for: "gastrointestinal discomfort on day of stool collection" 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.gastrointestinal discomfort on day of stool collection, Confounders controlled for: "stool sample travel 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.stool sample travel time, constipation, alcohol drinking