Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression
Abstract
The importance of gut commensal bacteria in maintaining immune homeostasis is increasingly understood. We recently described that alteration of the gut microflora can affect a population of Foxp3(+)T(reg) cells that regulate demyelination in experimental autoimmune encephalomyelitis (EAE), the experimental model of human multiple sclerosis. We now extend our previous observations on the role of commensal bacteria in CNS demyelination, and we demonstrate that Bacteroides fragilis producing a bacterial capsular polysaccharide Ag can protect against EAE. Recolonization with wild type B. fragilis maintained resistance to EAE, whereas reconstitution with polysaccharide A-deficient B. fragilis restored EAE susceptibility. Enhanced numbers of Foxp3(+)T(reg) cells in the cervical lymph nodes were observed after intestinal recolonization with either strain of B. fragilis. Ex vivo, CD4(+)T cells obtained from mice reconstituted with wild type B. fragilis had significantly enhanced rates of conversion into IL-10-producing Foxp3(+)T(reg) cells and offered greater protection against disease. Our results suggest an important role for commensal bacterial Ags, in particular B. fragilis expressing polysaccharide A, in protecting against CNS demyelination in EAE and perhaps human multiple sclerosis.
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Up-regulation of ENTPD1 has been implicated in the protective effect of PSA in experimental autoimmune encephalomyelitis.
“the up-regulation of ENTPD1 has been implicated in the protective effect of PSA in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (Ochoa-Reparaz et al., 2010; Y. Wang et al., 2014).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Ochoa-Reparaz et al., 2010
B. fragilis and Clostridial consortium correct symptoms of intestinal disease and multiple sclerosis in animal models.
“By this mechanism, B. fragilis and Clostridial consortium sufficiently correct symptoms of intestinal disease and multiple sclerosis in animal models (74, 75) and continue to be tested for clinical translation into patient populations.”
From Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder (2017) · cites this paper as [75]
The altered microbiota of patients could transfer the disease from a human host to a mouse host.
“Of extreme relevance, the altered microbiota of patients could transfer the disease from a human host to a mouse host (113, 116–120).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [116]
Mice treated with antibiotics alone or recolonized with the PSA-wild-type strain of B. fragilis were protected against experimental autoimmune encephalomyelitis, whereas mice recolonized with ΔPSA B. fragilis and vehicle-treated controls developed the disease.
“Mice treated with antibiotics alone or recolonized with the PSA-wild-type strain of B. fragilis were protected against disease, whereas the mice recolonized with ΔPSA B. fragilis and as well the vehicle-treated control group developed the disease (116).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [116]
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- Authors
- Ochoa-Repáraz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H.
- Affiliations
- Section of Neurology, Department of Medicine , Lebanon, NH 03756
- Department of Microbiology and Immunology, Dartmouth Medical School , Lebanon, NH 03756
- Brigham and Women's Hospital (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-01
- Volume
- 185
- Issue
- 7
- Pages
- 4101-4108
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2118649010
- Cited by
- 367
- References
- 31
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 18 · 2023: 23 · 2022: 24 · 2021: 30 · 2020: 27 · 2019: 24 · 2018: 37 · 2017: 34 · 2016: 31 · 2015: 21 · 2014: 22 · 2013: 18 · 2012: 16
- FWCI
- 11.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dartmouth College
- U.S. Public Health Service
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Bacteroides fragilis, polysaccharide A, experimental autoimmune encephalomyelitis, multiple sclerosis, central nervous system demyelination, gut commensal bacteria, Foxp3+ regulatory T cells, IL-10, immune tolerance, gut microbiota
- MeSH terms
- Animals, Antigens, Bacterial, Bacteroides fragilis, Cell Separation, Encephalomyelitis, Autoimmune, Experimental, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Intestinal Mucosa, Bacterial Capsules, Reverse Transcriptase Polymerase Chain Reaction, Mice
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