Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson's Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Nishiwaki H, Hamaguchi T, Ito M, Ishida T, Maeda T, Kashihara K, Tsuboi Y, Ueyama J, Shimamura T, Mori H, Kurokawa K, Katsuno M, Hirayama M, Ohno K
Journal
mSystems
Year
2020
Keywords:
Parkinson’s disease, gut microbiota, meta-analysis, rapid-eye-movement behavior disorder, topic model
Gut dysbiosis has been repeatedly reported in Parkinson's disease (PD) but only once in idiopathic rapid-eye-movement sleep behavior disorder (iRBD) from Germany. Abnormal aggregation of α-synuclein fibrils causing PD possibly starts from the intestine, although this is still currently under debate. iRBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in iRBD. We analyzed gut microbiota in 26 iRBD patients and 137 controls by 16S rRNA sequencing (16S rRNA-seq). Our iRBD data set was meta-analyzed with the German iRBD data set and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA sequencing (RNA-seq) analysis, revealed four enterotypes in controls, iRBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and iRBD, whereas they were less conserved in enterotypes observed in PD. Genus Akkermansia and family Akkermansiaceae were consistently increased in both iRBD in two countries and PD in five countries. Short-chain fatty acid (SCFA)-producing bacteria were not significantly decreased in iRBD in two countries. In contrast, we previously reported that recognized or putative SCFA-producing genera Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group were consistently decreased in PD in five countries. In α-synucleinopathy, increase of mucin-layer-degrading genus Akkermansia is observed at the stage of iRBD, whereas decrease of SCFA-producing genera becomes obvious with development of PD.IMPORTANCE Twenty studies on gut microbiota in PD have been reported, whereas only one study has been reported on iRBD from Germany. iRBD has the highest likelihood ratio to develop PD. Our meta-analysis of iRBD in Japan and Germany revealed increased mucin-layer-degrading genus Akkermansia in iRBD. Genus Akkermansia may increase the intestinal permeability, as we previously observed in PD patients, and may make the intestinal neural plexus exposed to oxidative stress, which can lead to abnormal aggregation of prion-like α-synuclein fibrils in the intestine. In contrast to PD, SCFA-producing bacteria were not decreased in iRBD. As SCFA induces regulatory T (Treg) cells, a decrease of SCFA-producing bacteria may be a prerequisite for the development of PD. We propose that prebiotic and/or probiotic therapeutic strategies to increase the intestinal mucin layer and to increase intestinal SCFA potentially retard the development of iRBD and PD.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Curated date: 2024/03/17
Curator: Aishat
Revision editor(s): Scholastica, Aleru Divine, Victoria, Aishat
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
- Sleep Disorder Disturbances, Sleep,disturbances, sleep,parasomnia,sleep disorder,Sleep Disorders,Sleep Disturbance,sleep disturbance,Sleep Disturbances,sleep disturbances,Sleep Disorder,sleep Disorder
- 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
- Rapid-eye-movement sleep behavior disorder (iRBD) patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD) diagnosed according to the International Classification of Sleep Disorders Criteria-Third Edition
- Group 0 sample size Number of subjects in the control (unexposed) group
- 137
- Group 1 sample size Number of subjects in the case (exposed) group
- 26
- 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
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- ANCOM
- Mann-Whitney (Wilcoxon)
- 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
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Source: Supplementary Table S2
Description: Read counts of genera normalized for 1 × 104 reads in controls and iRBD.
Abundance in Group 1: increased abundance in Rapid-eye-movement sleep behavior disorder (iRBD) patients
Revision editor(s): Aishat, Aleru Divine
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex, constipation, proton-pump inhibitor
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Source: Supplementary Table S4
Description: Generalized linear mixed model (GLMM) analysis to evaluate confounding factors of seven genera and two families that were significantly changed in iRBD compared to controls
Abundance in Group 1: increased abundance in Rapid-eye-movement sleep behavior disorder (iRBD) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Ruminococcus 2Ruminococcus 2 | ||
| Alistipes | ||
| Akkermansia | ||
| Ruminococcaceae UCG-004Ruminococcaceae UCG-004 | ||
| Family XIII AD3011 groupFamily XIII AD3011 group | ||
| Rikenellaceae | ||
| Akkermansiaceae |
Revision editor(s): Aleru Divine
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Differences from previous experiment shown
Subjects
- Group 0 sample size Number of subjects in the control (unexposed) group
- 2
- Group 1 sample size Number of subjects in the case (exposed) group
- 2
Lab analysis
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Not specified
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- Mixed-Effects Regression
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Source: Supplementary Table S6A and S6B
Description: Microbial signatures significantly increased in iRBD in two datasets at the genus and family levels (plotted in Fig. 3A)
Abundance in Group 1: increased abundance in Rapid-eye-movement sleep behavior disorder (iRBD) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia | ||
| Akkermansiaceae | ||
| Alistipes | ||
| Rikenellaceae | ||
| Ruminococcaceae UCG-004Ruminococcaceae UCG-004 | ||
| Family XIII AD3011 groupFamily XIII AD3011 group |
Revision editor(s): Aleru Divine
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Differences from previous experiment shown
Subjects
- Location of subjects
- Finland
- Germany
- Japan
- Russian Federation
- United States of America
- 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 1 name Corresponds to the case (exposed) group for case-control studies
- Parkinson's disease (PD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with idiopathic Parkinson's disease (PD) diagnosed according to the International Parkinson and Movement Disorder Society's PD criteria.51
- Group 0 sample size Number of subjects in the control (unexposed) group
- 5
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex, constipation, Confounders controlled for: "COMT inhibitor" 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
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-24
Source: Supplementary Table S6C
Description: Microbial signatures significantly decreased in PD at the genus level (plotted in Fig. 3C)
Abundance in Group 1: decreased abundance in Parkinson's disease (PD)
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium | ||
| Roseburia | ||
| Lachnospiraceae ND3007 groupLachnospiraceae ND3007 group |
Revision editor(s): Aleru Divine
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