Fecal microbiome alterations in treatment-naive de novo Parkinson's disease

From BugSigDB
Reviewed Marked as Reviewed by Atrayees on 2023-7-7
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Boertien JM, Murtomäki K, Pereira PAB, van der Zee S, Mertsalmi TH, Levo R, Nojonen T, Mäkinen E, Jaakkola E, Laine P, Paulin L, Pekkonen E, Kaasinen V, Auvinen P, Scheperjans F, van Laar T
Journal
NPJ Parkinson's disease
Year
2022
Gut microbiota alterations in Parkinson's disease (PD) have been found in several studies and are suggested to contribute to the pathogenesis of PD. However, previous results could not be adequately adjusted for a potential confounding effect of PD medication and disease duration, as almost all PD participants were already using dopaminergic medication and were included several years after diagnosis. Here, the gut microbiome composition of treatment-naive de novo PD subjects was assessed compared to healthy controls (HC) in two large independent case-control cohorts (n = 136 and 56 PD, n = 85 and 87 HC), using 16S-sequencing of fecal samples. Relevant variables such as technical batches, diet and constipation were assessed for their potential effects. Overall gut microbiome composition differed between PD and HC in both cohorts, suggesting gut microbiome alterations are already present in de novo PD subjects at the time of diagnosis, without the possible confounding effect of dopaminergic medication. Although no differentially abundant taxon could be replicated in both cohorts, multiple short chain fatty acids (SCFA) producing taxa were decreased in PD in both cohorts. In particular, several taxa belonging to the family Lachnospiraceae were decreased in abundance. Fewer taxonomic differences were found compared to previous studies, indicating smaller effect sizes in de novo PD.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees, LGeistlinger, Victoria

Subjects

Location of subjects
Netherlands
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
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
Dutch(NL) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the Movement Disorders Society (MDS) clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by FDOPA-PET or one-year follow-up if no FDOPA-PET was performed.
Group 0 sample size Number of subjects in the control (unexposed) group
85
Group 1 sample size Number of subjects in the case (exposed) group
136
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4-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).
centered log-ratio
Statistical test
ANCOM
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "stool frequency" 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.stool frequency

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3. Differentially abundant taxa between PD and HC in NL cohort..

Description: Differentially abundant taxa between PD and HC detected using ANCOM.


  • (A negative change indicates lower abundance in PD compared to HC)

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

NCBI Quality ControlLinks
Rikenellaceae

Revision editor(s): Fcuevas3, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3.

Description: Differentially abundant taxa between PD and HC detected using ANCOM.

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

NCBI Quality ControlLinks
Lachnoclostridium
Lachnospiraceae
Roseburia
Veillonellaceae

Revision editor(s): Fcuevas3, Atrayees

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Victoria

Differences from previous experiment shown

Subjects

Location of subjects
Finland


Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Finnish(FIN) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the MDS clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by [I-123]FP-CIT SPECT. [I-123]FP-CIT SPECT were analyzed with BRASS software (Hermes Medical Solutions AB, Stockholm, Sweden), in which a dopaminergic deficit was defined as more than two standard deviations below the reference mean in any of the six analyzed regions.
Group 0 sample size Number of subjects in the control (unexposed) group
87
Group 1 sample size Number of subjects in the case (exposed) group
56
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Recent antibiotics usage in the previous month.

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "number of reads" 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.number of reads

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3.

Description: Differentially abundant taxa between PD and HC detected using ANCOM

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

NCBI Quality ControlLinks
Christensenellaceae

Revision editor(s): Fcuevas3, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3.

Description: Differentially abundant taxa between PD and HC detected using ANCOM

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

NCBI Quality ControlLinks
Roseburia inulinivorans
Lachnoclostridium edouardi
Lachnospiraceae
Colidextribacter
Roseburia

Revision editor(s): Fcuevas3, Atrayees

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees, Victoria

Differences from previous experiment shown

Subjects

Location of subjects
Netherlands


Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Dutch(NL) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the Movement Disorders Society (MDS) clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by FDOPA-PET or one-year follow-up if no FDOPA-PET was performed.
Group 0 sample size Number of subjects in the control (unexposed) group
85
Group 1 sample size Number of subjects in the case (exposed) group
136

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "stool frequency" 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.stool frequency

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3.

Description: Differentially abundant taxa between PD and HC detected using DESeq2.

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

NCBI Quality ControlLinks
Clostridia

Revision editor(s): Fcuevas3, Atrayees

Experiment 4


Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Victoria

Differences from previous experiment shown

Subjects

Location of subjects
Finland


Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Finnish(FIN) Cohort: Parkinson's disease diagnosis by a movement disorder specialist according to the MDS clinical diagnostic criteria1, confirmed by a dopaminergic deficit quantified by [I-123]FP-CIT SPECT. [I-123]FP-CIT SPECT were analyzed with BRASS software (Hermes Medical Solutions AB, Stockholm, Sweden), in which a dopaminergic deficit was defined as more than two standard deviations below the reference mean in any of the six analyzed regions.
Group 0 sample size Number of subjects in the control (unexposed) group
87
Group 1 sample size Number of subjects in the case (exposed) group
56

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "stool consistency" 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.stool consistency, Confounders controlled for: "number of reads" 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.number of reads

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3.

Description: Differentially abundant taxa between PD and HC detected using DESeq2.

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

NCBI Quality ControlLinks
Akkermansiaceae
Eggerthellaceae

Revision editor(s): Fcuevas3, Atrayees

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-7

Curated date: 2023/06/03

Curator: Fcuevas3

Revision editor(s): Fcuevas3, Atrayees

Source: Table 3.

Description: Differentially abundant taxa between PD and HC detected using DESeq2.

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

NCBI Quality ControlLinks
Lachnospiraceae
Butyricicoccus
Acholeplasmataceae

Revision editor(s): Fcuevas3, Atrayees