Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis

Study information

Needs review

study design

meta-analysis

Citation

PMID PubMed identifier for scientific articles.

36593694

DOI Digital object identifier for electronic documents.

https://doi.org/10.1111/ene.15671

URI Uniform resource identifier for web resources.

Authors

Kleine Bardenhorst S, Cereda E, Severgnini M, Barichella M, Pezzoli G, Keshavarzian A, Desideri A, Pietrucci D, Aho VTE, Scheperjans F, Hildebrand F, Weis S, Egert M, Karch A, Vital M, Rübsamen N

Journal

European journal of neurology

Year

2023

Keywords:

Parkinson disease, brain-gut axis, dysbiosis, gastrointestinal microbiome, systematic review

BACKGROUND AND PURPOSE: The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity. METHODS: We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls. A workflow was designed to harmonize processing across all studies from bioinformatics processing to final statistical analysis using a Bayesian random-effects meta-analysis based on individual patient-level data. RESULTS: The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were most characteristic for PD-associated microbiota. CONCLUSIONS: Our study summarizes evidence that reduced levels of butyrate-producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This may allow potentially pathogenic metabolites to transit and enter the enteric nervous system.

Experiment 1

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Curated date: 2025/04/24

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Subjects

Location of subjects: China; Finland; Germany; Italy; 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 Control

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Participants were classified as Parkinson's Disease (PD) patients after the use of UK Brain Bank criteria for the diagnosis of Parkinson's Disease (PD)

Group 0 sample size Number of subjects in the control (unexposed) group: 751

Group 1 sample size Number of subjects in the case (exposed) group: 1092

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).: log transformation

Statistical test: ANCOM-BC

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

Alpha Diversity

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

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

Richness Number of species: unchanged

Signature 1

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Source: Figure 4

Description: Differentially abundant bacterial taxa in Parkinson's Disease patients

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

NCBI	Quality Control	Links
Acidaminobacter
Akkermansia
Desulfurispora
Eisenbergiella
Synergistaceae
Synergistes
Verrucomicrobiaceae
Verrucomicrobiia
Porphyromonadaceae

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Signature 2

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Source: Figure 4

Description: Differentially abundant bacterial taxa in Parkinson's Disease patients

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

NCBI	Quality Control	Links
Blautia
Faecalibacterium
Roseburia

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Experiment 2

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Curated date: 2025/07/02

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Differences from previous experiment shown

Subjects

Alpha Diversity

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

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

Richness Number of species: unchanged

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Source: Table 2

Description: Significant bacterial taxa identified while comparing individuals with Parkinson’s Disease (PD) to healthy controls

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

NCBI	Quality Control	Links
Acidaminobacter
Akkermansia
Desulfurispora
Eisenbergiella
Porphyromonadaceae
Synergistaceae
Synergistes
Verrucomicrobiia
Verrucomicrobiaceae
Peptococcaceae 2Peptococcaceae 2
Clostridiales incertae sedis XIIClostridiales incertae sedis XII
Lachnospiraceae