Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease

From BugSigDB
Reviewed Marked as Reviewed by Rimsha on 2022/05/15
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Lin CH, Chen CC, Chiang HL, Liou JM, Chang CM, Lu TP, Chuang EY, Tai YC, Cheng C, Lin HY, Wu MS
Journal
Journal of neuroinflammation
Year
2019
Keywords:
Cytokines, Dysbiosis, Gut microbiome, Neuroinflammation, Parkinson’s disease
OBJECTIVE: Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. METHODS: Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. RESULTS: Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03). CONCLUSIONS: This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.

Experiment 1


Reviewed Marked as Reviewed by Rimsha on 2022/05/15

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Rimsha, Fcuevas3, WikiWorks

Subjects

Location of subjects
Japan
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 without Parkinson's 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
PD was diagnosed according to the United Kingdom PD Society Brain Bank clinical diagnostic criteria.
Group 0 sample size Number of subjects in the control (unexposed) group
77
Group 1 sample size Number of subjects in the case (exposed) group
80
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Individuals currently taking antibiotics or probiotic supplements within 3 months of sample collection

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Matched on Factors on which subjects have been matched on in a case-control study
age, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, diet, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Rimsha on 2022/05/15

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3

Source: Figure 3A

Description: Taxonomic differences of fecal microbiota in PD and control groups

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

NCBI Quality ControlLinks
Porphyromonadaceae
Parabacteroides
Verrucomicrobiota
Verrucomicrobiaceae
Akkermansia
Verrucomicrobiales
Odoribacteraceae
Rikenellaceae
Butyricimonas
Deferribacteraceae
Alphaproteobacteria
Veillonella
Erysipelotrichia
Erysipelotrichales
Erysipelotrichaceae
Odoribacter
Mycoplasmatota
Mucispirillum
Deferribacteres
Bilophila
Enterococcaceae
Lactobacillaceae
Enterococcus
Lactobacillus
Mollicutes
Hyphomicrobiales

Revision editor(s): Fcuevas3

Signature 2

Reviewed Marked as Reviewed by Rimsha on 2022/05/15

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Rimsha, Fcuevas3

Source: Figure 3A.

Description: Taxonomic differences of fecal microbiota in PD and control groups

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

NCBI Quality ControlLinks
Faecalibacterium
Prevotella
Prevotellaceae

Revision editor(s): Rimsha, Fcuevas3

Experiment 2


Reviewed Marked as Reviewed by Rimsha on 2022/05/15

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Fcuevas3, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Participants with Parkinson's Disease with non-tremor subtypes
Group 1 name Corresponds to the case (exposed) group for case-control studies
Participants with Parkinson's Disease with tremor subtypes
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants with Parkinson's Disease with tremor subtypes.
Group 0 sample size Number of subjects in the control (unexposed) group
33
Group 1 sample size Number of subjects in the case (exposed) group
47

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Rimsha on 2022/05/15

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Rimsha, Fcuevas3

Source: Figure 4A.

Description: Taxonomic differences of fecal microbiota in non tremor and tremor groups.

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

NCBI Quality ControlLinks
Akkermansia
Clostridia
Clostridiales Family XIII bacterium
Bacillota
Verrucomicrobiota
Verrucomicrobiaceae
Verrucomicrobiae
Verrucomicrobiales

Revision editor(s): Rimsha, Fcuevas3

Signature 2

Reviewed Marked as Reviewed by Rimsha on 2022/05/15

Curated date: 2022/01/22

Curator: Fcuevas3

Revision editor(s): Rimsha, Fcuevas3

Source: Figure 4A.

Description: Taxonomic differences of fecal microbiota in PD and control groups

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

NCBI Quality ControlLinks
Alcaligenaceae
Bacteroidales
Bacteroidota
Bacteroidia
Cupriavidus
Desulfovibrio
Flavobacterium
Mogibacterium
Propionibacterium
Sutterella

Revision editor(s): Rimsha, Fcuevas3