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Published on: August 8, 2014
The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model
Sukayna Fadlallah1, Elio R Bitar1, Hadi Hussein1,2
1Department of Experimental Pathology, Immunology, and Microbiology, American University of Beirut , Beirut, Lebanon.
Importance:
Epstein-Barr virus (EBV) DNA alters the composition and diversity of the gut microbiota in a rheumatoid arthritis (RA) mouse model. These induced changes are associated with enhanced severity of symptoms. This better understanding of the various factors involved in the development of RA will possibly help in creating individualized treatments for RA patients including target mediators triggered by viral DNA. Given that a large swathe of the population harbors EBV, a significant proportion of subjects with arthritis may benefit from possible approaches that target EBV or mediators triggered by this virus.
Insights
Epstein-Barr virus DNA alters gut microbiota diversity and composition, worsening rheumatoid arthritis (RA) severity in a mouse model. These changes may offer new therapeutic targets for RA patients.
Area of Science:
- Microbiology
- Immunology
- Rheumatology
Background:
- Epstein-Barr virus (EBV) DNA is implicated in autoimmune diseases via proinflammatory cytokines.
- Cytokines can induce colonic microbiota dysbiosis, a risk factor for rheumatoid arthritis (RA).
- The specific role of EBV DNA in modulating gut microbiota and exacerbating arthritis remains unclear.
Purpose of the Study:
- To investigate the role of EBV DNA in altering intestinal microbiota composition.
- To determine if EBV DNA exacerbates arthritis severity in a mouse model.
- To explore the potential of targeting EBV or its mediators for RA treatment.
Main Methods:
- Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water.
- Fecal samples were analyzed using 16S rRNA sequencing to assess colonic microbiota composition.
- Immune cell analysis (IL-17A, FOXP3, IFNγ co-expression) and fecal microbiota transplantation were performed.
Main Results:
- EBV DNA significantly altered gut microbiota alpha diversity, increasing richness (Chao1) and decreasing diversity (Shannon index) in the RA mouse model.
- The EBV DNA-exacerbated arthritic group showed the highest number of altered microbial genera and increased co-expression of IL-17A, FOXP3, and IFNγ.
- Transplantation of microbiota from EBV DNA-exacerbated arthritic mice led to higher RA incidence and severity in recipient mice.
Conclusions:
- EBV DNA alters gut microbiota composition and diversity, contributing to increased rheumatoid arthritis severity.
- Induced microbial changes are associated with specific immune cell profiles in the colon.
- Targeting EBV or its induced mediators presents a potential therapeutic strategy for RA patients.
