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The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model
Epstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581075/ https://www.ncbi.nlm.nih.gov/pubmed/37615438 http://dx.doi.org/10.1128/spectrum.02042-23 |
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author | Fadlallah, Sukayna Bitar, Elio R. Hussein, Hadi Jallad, Mary-Ann Matar, Ghassan M. Rahal, Elias A. |
author_facet | Fadlallah, Sukayna Bitar, Elio R. Hussein, Hadi Jallad, Mary-Ann Matar, Ghassan M. Rahal, Elias A. |
author_sort | Fadlallah, Sukayna |
collection | PubMed |
description | Epstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we investigated the role that EBV DNA may play in modulating the intestinal microbiota and consequent exacerbation of arthritis in a mouse model. Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water. Fecal samples were collected from arthritic and control mice, and 16S rRNA sequencing was performed to determine the effect of EBV DNA on the composition of colonic microbiota. EBV DNA causes a change in the alpha diversity of the microbiota resulting in an increased Chao1 microbial richness and decreased Shannon diversity index in the RA mouse model. In addition, the abundance of particular genera/genus clusters was significantly altered among the various groups, with the EBV DNA-exacerbated arthritic group having the highest number of altered genera/genus cluster abundances. This group also had the highest number of cells co-expressing IL-17A, FOXP3, and IFNγ in the colons. Antimicrobial-cleared mice transplanted with fecal samples from EBV DNA-exacerbated arthritic mice showed a higher incidence and enhanced severity of RA compared to those transplanted with fecal samples from water or collagen-treated mice. 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. |
format | Online Article Text |
id | pubmed-10581075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-105810752023-10-18 The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model Fadlallah, Sukayna Bitar, Elio R. Hussein, Hadi Jallad, Mary-Ann Matar, Ghassan M. Rahal, Elias A. Microbiol Spectr Research Article Epstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we investigated the role that EBV DNA may play in modulating the intestinal microbiota and consequent exacerbation of arthritis in a mouse model. Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water. Fecal samples were collected from arthritic and control mice, and 16S rRNA sequencing was performed to determine the effect of EBV DNA on the composition of colonic microbiota. EBV DNA causes a change in the alpha diversity of the microbiota resulting in an increased Chao1 microbial richness and decreased Shannon diversity index in the RA mouse model. In addition, the abundance of particular genera/genus clusters was significantly altered among the various groups, with the EBV DNA-exacerbated arthritic group having the highest number of altered genera/genus cluster abundances. This group also had the highest number of cells co-expressing IL-17A, FOXP3, and IFNγ in the colons. Antimicrobial-cleared mice transplanted with fecal samples from EBV DNA-exacerbated arthritic mice showed a higher incidence and enhanced severity of RA compared to those transplanted with fecal samples from water or collagen-treated mice. 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. American Society for Microbiology 2023-08-24 /pmc/articles/PMC10581075/ /pubmed/37615438 http://dx.doi.org/10.1128/spectrum.02042-23 Text en Copyright © 2023 Fadlallah et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Fadlallah, Sukayna Bitar, Elio R. Hussein, Hadi Jallad, Mary-Ann Matar, Ghassan M. Rahal, Elias A. The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model |
title | The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model |
title_full | The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model |
title_fullStr | The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model |
title_full_unstemmed | The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model |
title_short | The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model |
title_sort | interplay between epstein-barr virus dna and gut microbiota in the development of arthritis in a mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581075/ https://www.ncbi.nlm.nih.gov/pubmed/37615438 http://dx.doi.org/10.1128/spectrum.02042-23 |
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