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Updated: Jun 28, 2026
Therapeutic Evaluation of Fecal Microbiota Transplantation in an Interleukin 10-Deficient Mouse Model
Published on: April 6, 2022
NKT cell-dependent amelioration of a mouse model of multiple sclerosis by altering gut flora
Hiroaki Yokote1, Sachiko Miyake, J Ludovic Croxford
1Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Abstract:
Improved hygiene has been suggested to influence certain autoimmune disorders, such as multiple sclerosis. In this study, we addressed whether altering the composition of gut flora may affect susceptibility to experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We administered a mixture of non-absorbing antibiotics, kanamycin, colistin, and vancomycin (KCV), orally to mice induced to develop EAE. The antibiotic treatment, beginning 1 week prior to sensitization, altered the composition of gut flora and, intriguingly, also ameliorated the development of EAE. While this result was associated with a reduced production of pro-inflammatory cytokines from the draining lymph node cells, a reduction of mesenteric Th17 cells was found to correlate with disease suppression. In addition, we found that Valpha14 invariant NKT (iNKT) cells were necessary for maintaining the mesenteric Th17 cells. The homologous effects of KCV treatment and iNKT cell depletion led us to speculate that KCV treatment may suppress EAE by altering the function of iNKT cells. Consistent with this hypothesis, KCV treatment did not suppress EAE that was induced in iNKT cell-deficient mice, although it was efficacious in mice that lacked Valpha19 mucosal-associated invariant T cells. Thus, gut flora may influence the development of EAE in a way that is dependent on iNKT cells, which has significant implications for the prevention and treatment of autoimmune diseases.
Insights
Altering gut flora with antibiotics ameliorated experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. This effect was linked to invariant NKT (iNKT) cells, suggesting a new therapeutic avenue for autoimmune diseases.
Area of Science:
- Immunology
- Microbiology
- Neuroscience
Background:
- Autoimmune disorders, including multiple sclerosis (MS), are increasingly linked to hygiene and gut microbiome alterations.
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for studying MS pathogenesis.
Purpose of the Study:
- To investigate the impact of modifying gut flora composition on susceptibility to EAE.
- To explore the underlying mechanisms by which gut flora influences autoimmune disease development.
Main Methods:
- Oral administration of a non-absorbing antibiotic cocktail (kanamycin, colistin, vancomycin - KCV) to mice prior to EAE induction.
- Analysis of gut flora composition, pro-inflammatory cytokine production, and specific immune cell populations (Th17, iNKT cells).
- Evaluation of EAE development in antibiotic-treated mice and in mice deficient in specific immune cell types (iNKT, Valpha19 MALT).
Main Results:
- KCV treatment significantly altered gut flora and ameliorated EAE development.
- Antibiotic treatment reduced pro-inflammatory cytokine production and mesenteric Th17 cells, correlating with disease suppression.
- EAE suppression by KCV was dependent on Valpha14 invariant NKT (iNKT) cells, but not Valpha19 mucosal-associated invariant T cells.
Conclusions:
- Gut flora composition plays a crucial role in the development of EAE, a model for MS.
- The influence of gut flora on EAE is mediated, at least in part, through iNKT cells.
- Targeting gut microbiota represents a potential therapeutic strategy for autoimmune diseases, leveraging the iNKT cell pathway.
