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Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters
Open accessAbstract
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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![Fig 5 Phylogenetic tree of 14 clostridial species exhibiting significant differences among groups and several known species. The neighbor-joining method was used to construct the phylogenetic tree. Numbers at each node indicate the bootstrap support (1,000 replicates). Those written in red letters are 14 clostridial species having a significant difference in relative abundance between HC40 and MS20 samples. Treg-inducing strains are indicated by “St” and are written in blue letters [13].](/paper-figures/cabefd3c1856464fb7f6cfb12c4b3815/dysbiosis-in-the-gut-microbiota-of-patients-with-multiple-sclerosis-with-a-figure-5.jpg)
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“Bacteria belonging to the Clostridia family contribute to the suppression of pathological autoimmunity (134, 139–143).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [134]
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“Interestingly, even MS patients with active disease have an altered microbiota compared to patients in the remission phase, which in turn have a microbiota more similar to healthy controls (25, 134–138).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [134]
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Metadata
- 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
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-09-14
- Volume
- 10
- Issue
- 9
- Pages
- e0137429
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4569432
- 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
- gold
- doi.org
- Licence
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Gastroenterology › 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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