Colonic bacterial composition in Parkinson's disease

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Reviewed Marked as Reviewed by Atrayees on 2023-8-15
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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 (if applicable)
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
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
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

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

Curated date: 2023/05/24

Curator: Fcuevas3

Revision editor(s): Fcuevas3

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 ControlLinks
Akkermansia
Bacteroidaceae
Bacteroides
Bacteroidia
Clostridiaceae
Oscillospira
Pseudomonadota
Verrucomicrobiaceae
Verrucomicrobiota

Revision editor(s): Fcuevas3

Signature 2

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

Curated date: 2023/05/24

Curator: Fcuevas3

Revision editor(s): Fcuevas3

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 ControlLinks
Bacillota
Blautia
Coprobacillaceae
Coprococcus
Dorea
Lachnospiraceae
Roseburia

Revision editor(s): Fcuevas3

Experiment 2


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

Curated date: 2023/05/24

Curator: Fcuevas3

Revision editor(s): Fcuevas3

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


Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species
increased

Signature 1

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

Curated date: 2023/05/24

Curator: Fcuevas3

Revision editor(s): Fcuevas3

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

Description: Sigmoid Mucosa: Parkinson's Disease vs. Healthy Controls.

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

NCBI Quality ControlLinks
Oxalobacteraceae
Ralstonia

Revision editor(s): Fcuevas3

Signature 2

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

Curated date: 2023/05/24

Curator: Fcuevas3

Revision editor(s): Fcuevas3

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

Description: Sigmoid Mucosa: Parkinson's Disease vs. Healthy Controls

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

NCBI Quality ControlLinks
Coprobacillaceae
Dorea
Faecalibacterium

Revision editor(s): Fcuevas3