Gut microorganisms act together to exacerbate inflammation in spinal cords
Abstract
Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis 1. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)2,3, as well as human studies 4-6, have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.
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Ampicillin administration alone ameliorated experimental autoimmune encephalomyelitis development with a reduction of proliferating CD4+ autoreactive T cells.
“Lately, in the classical acute EAE model, ampicillin administration alone ameliorated the EAE development (152) with a reduction of proliferating CD4+ autoreactive T cells.”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [152]
Mice bearing a T cell receptor specific for myelin-oligodendrocyte glycoprotein (2D2 mice) showed a higher number of CD4+ T cells in the small intestinal lamina propria compared to their wild-type counterpart.
“Mice bearing a T cell-receptor (TCR) specific for myelin-oligodendrocyte glycoprotein (MOG) (2D2 mice) showed higher number of CD4+ T cells in the small intestinal lamina propria compared to their wild-type counterpart (152).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [152]
Bi-colonization with Allobaculum and L. reuteri together activated MOG-specific T cells toward a pathogenic Th17 phenotype and worsened experimental autoimmune encephalomyelitis, with demyelination and cell infiltration in the spinal cord.
“However, the bi-colonization with Allobaculum and L. reuteri together activated MOG-specific T cells toward a pathogenic Th17 phenotype and worsened EAE, with demyelination and cell infiltration in the spinal cord (152).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [152]
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- Authors
- Miyauchi, E., Kim, S.-W., Suda, W., Kawasumi, M., Onawa, S., Taguchi-Atarashi, N., Morita, H., Taylor, T. D., Hattori, M., & Ohno, H.
- Affiliations
- RIKEN Center for Integrative Medical Sciences (JP)
- Okayama University (JP)
- Waseda University (JP)
- Corresponding author
- Ohno, Hiroshi
- Venue
- Nature
- Published
- 2020-08-26
- Volume
- 585
- Issue
- 7823
- Pages
- 102-106
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3080459086
- Cited by
- 268
- References
- 37
- Citations by year
- 2026: 24 · 2025: 41 · 2024: 53 · 2023: 57 · 2022: 57 · 2021: 28 · 2020: 8
- FWCI
- 24.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (19K05907, 19H01030)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- gut microbiota, multiple sclerosis, experimental autoimmune encephalomyelitis, myelitis, myelin oligodendrocyte glycoprotein, autoreactive T cells, Erysipelotrichaceae, Lactobacillus reuteri, Th17 cells, germ-free mice, co-colonization, autoimmune disease pathogenesis
- MeSH terms
- Gastrointestinal Microbiome, Animals, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Germ-Free Life, Inflammation, Intestine, Small, Male, Multiple Sclerosis, Spinal Cord, T-Lymphocytes, Mice, Limosilactobacillus reuteri, Th17 Cells, Myelin-Oligodendrocyte Glycoprotein
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