Colonic bacterial composition in Parkinson's disease

Study information

Reviewed Marked as Reviewed by Atrayees on 2023-8-15

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

26179554

DOI Digital object identifier for electronic documents.

10.1002/mds.26307

URI

Authors

Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E, Shannon KM

Journal

Movement disorders : official journal of the Movement Disorder Society

Year

2015

Keywords:

a-synuclein, colonic mucosa and feces, dysbiosis, microbiota, putative butyrate producing short-chain fatty acids

INTRODUCTION: We showed that Parkinson's disease (PD) patients have alpha-synuclein (α-Syn) aggregation in their colon with evidence of colonic inflammation. If PD patients have altered colonic microbiota, dysbiosis might be the mechanism of neuroinflammation that leads to α-Syn misfolding and PD pathology. METHODS: Sixty-six sigmoid mucosal biopsies and 65 fecal samples were collected from 38 PD patients and 34 healthy controls. Mucosal-associated and feces microbiota compositions were characterized using high-throughput ribosomal RNA gene amplicon sequencing. Data were correlated with clinical measures of PD, and a predictive assessment of microbial community functional potential was used to identify microbial functions. RESULTS: The mucosal and fecal microbial community of PD patients was significantly different than control subjects, with the fecal samples showing more marked differences than the sigmoid mucosa. At the taxonomic level of genus, putative, "anti-inflammatory" butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia were significantly more abundant in feces of controls than PD patients. Bacteria from the genus Faecalibacterium were significantly more abundant in the mucosa of controls than PD. Putative, "proinflammatory" Proteobacteria of the genus Ralstonia were significantly more abundant in mucosa of PD than controls. Predictive metagenomics indicated that a large number of genes involved in metabolism were significantly lower in the PD fecal microbiome, whereas genes involved in lipopolysaccharide biosynthesis and type III bacterial secretion systems were significantly higher in PD patients. CONCLUSION: This report provides evidence that proinflammatory dysbiosis is present in PD patients and could trigger inflammation-induced misfolding of α-Syn and development of PD pathology.

Experiment 1

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Reviewed Marked as Reviewed by Atrayees on 2023-8-15

Curated date: 2023/05/24

Curator: Fcuevas3

Revision editor(s): Fcuevas3

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 control volunteers

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Parkinson's disease was diagnosed according to the UK Brain Bank Criteria.

Group 0 sample size Number of subjects in the control (unexposed) group: 34

Group 1 sample size Number of subjects in the case (exposed) group: 38

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): The use of probiotics or antibiotics within three months prior to sample collection.

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4-V4

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

Signature 1

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Source: TABLE 1. Relative increased abundance of sequences derived from individual taxa

Description: Feces: Parkinson's disease vs. Healthy controls.

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

NCBI	Quality Control	Links
Akkermansia
Bacteroidaceae
Bacteroides
Bacteroidia
Clostridiaceae
Oscillospira
Pseudomonadota
Verrucomicrobiaceae
Verrucomicrobiota

Revision editor(s): Fcuevas3

Signature 2

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Source: TABLE 1. Relative decreased abundance of sequences derived from individual taxa

Description: Feces: Parkinson's Disease vs. Healthy Controls

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

NCBI	Quality Control	Links
Bacillota
Blautia
Coprobacillaceae
Coprococcus
Dorea
Lachnospiraceae
Roseburia

Revision editor(s): Fcuevas3

Experiment 2

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Curated date: 2023/05/24

Curator: Fcuevas3

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Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Colonic mucosa Colon mucosa,Colon mucous membrane,Colonic mucosa,Colonic mucous membrane,Large bowel mucosa,Mucosa of colon,Mucosa of large bowel,colonic mucosa