Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters

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Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T
Journal
PloS one
Year
2015
The pathogenesis of multiple sclerosis (MS), an autoimmune disease affecting the brain and spinal cord, remains poorly understood. Patients with MS typically present with recurrent episodes of neurological dysfunctions such as blindness, paresis, and sensory disturbances. Studies on experimental autoimmune encephalomyelitis (EAE) animal models have led to a number of testable hypotheses including a hypothetical role of altered gut microbiota in the development of MS. To investigate whether gut microbiota in patients with MS is altered, we compared the gut microbiota of 20 Japanese patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the HC18 subjects repeatedly provided fecal samples over the course of months (158 samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS. Furthermore, we found 21 species that showed significant differences in relative abundance between the MS20 and HC40 samples. On comparing MS samples to the 158 longitudinal HC18 samples, the differences were found to be reproducibly significant for most of the species. These taxa comprised primarily of clostridial species belonging to Clostridia clusters XIVa and IV and Bacteroidetes. The phylogenetic tree analysis revealed that none of the clostridial species that were significantly reduced in the gut microbiota of patients with MS overlapped with other spore-forming clostridial species capable of inducing colonic regulatory T cells (Treg), which prevent autoimmunity and allergies; this suggests that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions. Correcting the dysbiosis and altered gut microbiota might deserve consideration as a potential strategy for the prevention and treatment of MS.

Experiment 1


Needs review

Curated date: 2024/10/06

Curator: Rahila

Revision editor(s): Rahila

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
Multiple sclerosis Disseminated Sclerosis,generalized multiple sclerosis,insular sclerosis,MS,MS (Multiple Sclerosis),multiple sclerosis,MULTIPLE SCLEROSIS ACUTE FULMINATING,Multiple Sclerosis, Acute Fulminating,Sclerosis, Disseminated,Sclerosis, Multiple,Multiple sclerosis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy subjects (controls)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Multiple sclerosis (MS),
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Japanese patients with relapsing-remitting (RR) MS
Group 0 sample size Number of subjects in the control (unexposed) group
40
Group 1 sample size Number of subjects in the case (exposed) group
20
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None of the subjects was treated with antibiotics during collection of fecal samples.

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V2
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Welch's 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

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/07

Curator: Rahila

Revision editor(s): Rahila

Source: S2_Fig.tif

Description: Fold-change in the relative abundance of 21 species showing significant differences between HC40 and MS20 samples.

Abundance in Group 1: increased abundance in Multiple sclerosis (MS),

NCBI Quality ControlLinks
Streptococcus thermophilus
Eggerthella lenta
Streptococcus salivarius

Revision editor(s): Rahila

Signature 2

Needs review

Curated date: 2024/10/07

Curator: Rahila

Revision editor(s): Rahila

Source: S2_Fig.tif

Description: Fold-change in the relative abundance of 21 species showing significant differences between HC40 and MS20 samples.

Abundance in Group 1: decreased abundance in Multiple sclerosis (MS),

NCBI Quality ControlLinks
Agathobacter rectalis ATCC 33656
Anaerostipes hadrus
Bacteroides stercoris
Clostridiaceae bacterium SH032
Clostridium sp.
Clostridium sp. ID5
Clostridium sp. RT8
Desulfotomaculum sp. CYP1
Faecalibacterium prausnitzii
Lachnospira pectinoschiza
Megamonas funiformis YIT 11815
Phocaeicola coprocola
Phocaeicola coprophilus
Roseburia sp. 1120
Segatella copri DSM 18205
Sutterella wadsworthensis 2_1_59BFAA
[Lactobacillus] rogosae
butyrate-producing bacterium A2-175
butyrate-producing bacterium SL7/1

Revision editor(s): Rahila

Experiment 2


Needs review

Curated date: 2024/10/07

Curator: Rahila

Revision editor(s): Rahila

Differences from previous experiment shown

Subjects

Group 0 sample size Number of subjects in the control (unexposed) group
18

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/07

Curator: Rahila

Revision editor(s): Rahila

Source: Fig 6

Description: Fold-change in the abundance of 21 species using longitudinal HC18 samples.

Abundance in Group 1: increased abundance in Multiple sclerosis (MS),

NCBI Quality ControlLinks
Streptococcus thermophilus
Eggerthella lenta
Streptococcus salivarius

Revision editor(s): Rahila

Signature 2

Needs review

Curated date: 2024/10/07

Curator: Rahila

Revision editor(s): Rahila

Source: Fig 6

Description: Fold-change in the abundance of 21 species using longitudinal HC18 samples.

Abundance in Group 1: decreased abundance in Multiple sclerosis (MS),

NCBI Quality ControlLinks
Agathobacter rectalis
Anaerostipes hadrus
Bacteroides stercoris
Clostridiaceae bacterium SH032
Clostridium sp.
Clostridium sp. RT8
Desulfotomaculum sp. CYP1
Faecalibacterium prausnitzii
Lachnospira pectinoschiza
Megamonas funiformis YIT 11815
Phocaeicola coprocola
Phocaeicola coprophilus
Roseburia sp. 1120
Segatella copri DSM 18205
Sutterella wadsworthensis
[Lactobacillus] rogosae
butyrate-producing bacterium A2-175
butyrate-producing bacterium SL7/1
Clostridium sp. ID5

Revision editor(s): Rahila