Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson's Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder

From BugSigDB
Needs review
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


Needs review

Curated date: 2024/03/17

Curator: Aishat

Revision editor(s): Aishat, Scholastica, Victoria

Subjects

Location of subjects
Germany
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
Intestine Bowel,Intestinal tract,Intestine,intestine
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
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
PERMANOVA
T-Test
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
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

Needs review

Curated date: 2024/03/17

Curator: Aishat

Revision editor(s): Aishat

Source: Figure 4

Description: Read counts of genera Akkermansia, Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group normalized for 1 × 104 reads in controls, iRBD, and Hoehn and Yahr scales 1 to 5.

Abundance in Group 1: increased abundance in Rapid-eye-movement sleep behavior disorder (iRBD) patients

NCBI Quality ControlLinks

Revision editor(s): Aishat

Signature 2

Needs review

Curated date: 2024/03/17

Curator: Aishat

Revision editor(s): Aishat

Source: Figure 4

Description: Read counts of genera Akkermansia, Faecalibacterium, Roseburia, and Lachnospiraceae ND3007 group normalized for 1 × 104 reads in controls, iRBD, and Hoehn and Yahr scales 1 to 5.

Abundance in Group 1: decreased abundance in Rapid-eye-movement sleep behavior disorder (iRBD) patients

NCBI Quality ControlLinks
Akkermansia
Faecalibacterium
Roseburia

Revision editor(s): Aishat