Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Aho VTE, Pereira PAB, Voutilainen S, Paulin L, Pekkonen E, Auvinen P, Scheperjans F
Journal
EBioMedicine
Year
2019
Keywords:
Disease progression, Gut microbiota, Gut-brain-axis, Parkinson's disease
BACKGROUND: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach. METHODS: We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2·25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing. FINDINGS: We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients. INTERPRETATION: The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progression, a longer follow-up period is required to confirm these findings.

Experiment 1


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Aiyshaaaa, Folakunmi, ChiomaBlessing

Subjects

Location of subjects
Finland
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 at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Participants with Parkinson's Disease at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Parkinson's disease at baseline.
Group 0 sample size Number of subjects in the control (unexposed) group
64
Group 1 sample size Number of subjects in the case (exposed) group
64
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None.

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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
ANCOM
DESeq2
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
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
body mass index, irritable bowel syndrome

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Source: Table 8, Supplemental. Table S4C

Description: Taxa that are differentially abundant between control and PD groups, according to ANCOM and DESeq2 at Baseline

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

NCBI Quality ControlLinks
Alistipes
Bifidobacteriaceae
Bifidobacterium
Romboutsia
Clostridium_XIVaClostridium_XIVa

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Source: Table 8, Supplemental. Table S4C

Description: Taxa that are differentially abundant between control and PD groups, according to ANCOM and DESeq2 at Baseline

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

NCBI Quality ControlLinks
Blautia
Butyricimonas
Porphyromonadaceae
Prevotella
Veillonellaceae
Clostridium_XVIIIClostridium_XVIII
Dialister

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Folakunmi, LGeistlinger, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Stable PD patients at follow up
Group 1 name Corresponds to the case (exposed) group for case-control studies
Progressed PD patients at follow up
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with progressed Parkinson's disease, defined based on between-timepoint change in Unified Parkinson's Disease Rating Scale (UPDRS) I-III sum and total medication load calculated using the Levodopa Equivalent Dose (LED).
Group 0 sample size Number of subjects in the control (unexposed) group
41
Group 1 sample size Number of subjects in the case (exposed) group
15
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "COMT inhibitor use" 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.COMT inhibitor use

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Source: Table 9: Follow up.

Description: Summary of differential abundance results contrasting follow-up progressed and stable PD patients

Abundance in Group 1: increased abundance in Progressed PD patients at follow up

NCBI Quality ControlLinks
Bifidobacterium
Anaeroplasmataceae
Asteroleplasma
unclassified Lachnospiraceae
unclassified Eubacteriales
Clostridium IVClostridium IV

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2024/01/10

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 9: Follow-up

Description: Summary of differential abundance results contrasting follow-up progressed and stable PD patients

Abundance in Group 1: decreased abundance in Progressed PD patients at follow up

NCBI Quality ControlLinks
Prevotella
Phascolarctobacterium
Coprococcus
Desulfovibrio

Revision editor(s): ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Lwaldron, Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls at time of follow-up
Group 1 name Corresponds to the case (exposed) group for case-control studies
Participants with Parkinson's Disease at time of follow-up
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants with Parkinson's Disease at time of follow-up
Group 0 sample size Number of subjects in the control (unexposed) group
64
Group 1 sample size Number of subjects in the case (exposed) group
64
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None.

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
body mass index, irritable bowel syndrome

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Source: Table 8, Supplemental. Table S4C

Description: Taxa that are differentially abundant between control and PD groups, according to ANCOM and DESeq2 at Follow-up.

Abundance in Group 1: increased abundance in Participants with Parkinson's Disease at time of follow-up

NCBI Quality ControlLinks
Bifidobacteriaceae
Bifidobacterium
Clostridium_IVClostridium_IV
Clostridium_XIVaClostridium_XIVa
Romboutsia

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-10

Curated date: 2023/02/02

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Source: Table 8, Supplemental. Table S4C

Description: Taxa that are differentially abundant between control and PD groups, according to ANCOM and DESeq2 at Follow-up.

Abundance in Group 1: decreased abundance in Participants with Parkinson's Disease at time of follow-up

NCBI Quality ControlLinks
Bacteroides
Prevotella
Prevotellaceae
Puniceicoccaceae
Roseburia
Ruminococcus
Clostridium_XIVaClostridium_XIVa
Porphyromonadaceae
Dialister
Veillonellaceae

Revision editor(s): Fcuevas3, Folakunmi, ChiomaBlessing

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2023/10/16

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Tremor-dominant phenotype (TD) at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Postural instability and gait difficulty (PIGD) phenotype at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Parkinson's disease patients with PIGD phenotype at baseline.
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
28
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
none

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2023/10/16

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing, MyleeeA

Source: Table S8 (B) in supplementary results.

Description: Differential abundance comparison results for disease phenotype (TD vs PIGD; within the PD patient group) at baseline.

Abundance in Group 1: decreased abundance in Postural instability and gait difficulty (PIGD) phenotype at baseline

NCBI Quality ControlLinks
Anaeroplasmataceae
Asteroleplasma
Bifidobacterium
Clostridium
Eisenbergiella
Enterobacteriaceae
Escherichia/Shigella sp.
Lactococcus
Prevotella
unclassified Deltaproteobacteria
unclassified Lachnospiraceae

Revision editor(s): Folakunmi, ChiomaBlessing, MyleeeA

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2023/10/16

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Source: Table S8 (B) in supplementary results.

Description: Differential abundance comparison results for disease phenotype (TD vs PIGD; within the PD patient group) at baseline.

Abundance in Group 1: increased abundance in Postural instability and gait difficulty (PIGD) phenotype at baseline

NCBI Quality ControlLinks
Bacteroides
Butyrivibrio
Gemmiger
unclassified Acidaminococcaceae
unclassified Lachnospiraceae
unclassified Eubacteriales
unclassified Bacteria

Revision editor(s): Folakunmi, ChiomaBlessing

Experiment 5


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2023/10/16

Curator: Folakunmi

Revision editor(s): Folakunmi, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Tremor-dominant phenotype (TD) at follow-up
Group 1 name Corresponds to the case (exposed) group for case-control studies
Postural instability and gait difficulty (PIGD) phenotype at follow-up
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Parkinson's disease patients with PIGD phenotype at follow-up
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
35

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2023/10/16

Curator: Folakunmi

Revision editor(s): Folakunmi, Peace Sandy, Hodan Issah, ChiomaBlessing

Source: Table S8 (B) in supplementary results.

Description: Differential abundance comparison results for disease phenotype (TD vs PIGD; within the PD patient group) at follow-up

Abundance in Group 1: decreased abundance in Postural instability and gait difficulty (PIGD) phenotype at follow-up

NCBI Quality ControlLinks
Barnesiella
Lactococcus
unclassified Clostridiaceae
unclassified Lachnospiraceae
unclassified Oscillospiraceae
unclassified Porphyromonadaceae
Clostridium XIVaClostridium XIVa
Anaeroplasmataceae
Asteroleplasma
unclassified Eubacteriales
unclassified Clostridia

Revision editor(s): Folakunmi, Peace Sandy, Hodan Issah, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2023/10/16

Curator: Folakunmi

Revision editor(s): Folakunmi

Source: Table S8 (B) in supplementary results.

Description: Differential abundance comparison results for disease phenotype (TD vs PIGD; within the PD patient group)

Abundance in Group 1: increased abundance in Postural instability and gait difficulty (PIGD) phenotype at follow-up

NCBI Quality ControlLinks
Akkermansia
unclassified Oscillospiraceae

Revision editor(s): Folakunmi

Experiment 6


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2024/01/11

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Stable PD patients at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Progressed PD patients at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with progressed Parkinson's disease, defined based on between-timepoint change in Unified Parkinson's Disease Rating Scale (UPDRS) I-III sum and total medication load calculated using the Levodopa Equivalent Dose (LED).
Group 0 sample size Number of subjects in the control (unexposed) group
41
Group 1 sample size Number of subjects in the case (exposed) group
15
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None

Lab analysis

Statistical Analysis

Statistical test
DESeq2
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
Confounders controlled for: "COMT inhibitor use" 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.COMT inhibitor use

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2024/01/11

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 9: Baseline

Description: Summary of differential abundance results contrasting follow-up progressed and stable PD patients

Abundance in Group 1: increased abundance in Progressed PD patients at baseline

NCBI Quality ControlLinks
Streptococcaceae
Streptococcus
unclassified Lachnospiraceae

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-1-11

Curated date: 2024/01/11

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Table 9: Baseline

Description: Summary of differential abundance results contrasting follow-up progressed and stable PD patients

Abundance in Group 1: decreased abundance in Progressed PD patients at baseline

NCBI Quality ControlLinks
Prevotella
Phascolarctobacterium
Coprococcus
Desulfovibrio

Revision editor(s): ChiomaBlessing