Cited by 810Gut microbiota and healthMultiple Sclerosis Research StudiesInflammatory Bowel Disease

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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Miyake, Sachiko, Kim, Sangwan, Suda, Wataru, Oshima, Kenshiro, Nakamura, Masakazu, Matsuoka, Takako, Chihara, Norio, Tomita, Atsuko +5 more·2015·PLoS ONE

Abstract

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.

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Authors
Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., Kim, S.-W., Morita, H., Hattori, M., & Yamamura, T.
Affiliations
  • Juntendo University (JP)
  • RIKEN Center for Integrative Medical Sciences (JP)
  • The University of Tokyo (JP)
  • National Institute of Neuroscience (JP)
  • Azabu University (JP)
Corresponding author
  • Hattori, Masahira
  • Yamamura, Takashi
Venue
PLoS ONE
Published
2015-09-14
Volume
10
Issue
9
Pages
e0137429
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2200372542
Cited by
809
References
41
Citations by year
2026: 49 · 2025: 61 · 2024: 83 · 2023: 68 · 2022: 91 · 2021: 89 · 2020: 89 · 2019: 76 · 2018: 85 · 2017: 76 · 2016: 38 · 2015: 2
FWCI
29.08
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Ministry of Health, Labour and Welfare
  • University of Tokyo
  • Japan Society for the Promotion of Science (24229006, 26293234)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
multiple sclerosis, gut microbiota, dysbiosis, Clostridium XIVa, Bacteroidetes, relapsing-remitting multiple sclerosis, experimental autoimmune encephalomyelitis, regulatory T cells, autoimmunity, 16S rRNA gene sequencing, fecal microbiota
MeSH terms
Gastrointestinal Microbiome, Adult, Clostridium, Female, Humans, Japan, Male, Multiple Sclerosis, RNA, Bacterial, RNA, Ribosomal, 16S, Sequence Analysis, RNA, Bacteroidetes, High-Throughput Nucleotide Sequencing, Dysbiosis

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