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Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness
Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were al...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832151/ https://www.ncbi.nlm.nih.gov/pubmed/31640184 http://dx.doi.org/10.3390/v11100968 |
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author | Seth, Ratanesh K. Maqsood, Rabia Mondal, Ayan Bose, Dipro Kimono, Diana Holland, LaRinda A. Janulewicz Lloyd, Patricia Klimas, Nancy Horner, Ronnie D. Sullivan, Kimberly Lim, Efrem S. Chatterjee, Saurabh |
author_facet | Seth, Ratanesh K. Maqsood, Rabia Mondal, Ayan Bose, Dipro Kimono, Diana Holland, LaRinda A. Janulewicz Lloyd, Patricia Klimas, Nancy Horner, Ronnie D. Sullivan, Kimberly Lim, Efrem S. Chatterjee, Saurabh |
author_sort | Seth, Ratanesh K. |
collection | PubMed |
description | Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were altered in GWI. The increased viral richness and alpha diversity correlated positively with gut bacterial dysbiosis and proinflammatory cytokines. Altered virome signature in GWI mice also had a concomitant weakening of intestinal epithelial tight junctions with a significant increase in Claudin-2 protein expression and decrease in ZO1 and Occludin mRNA expression. The altered virome signature in GWI, decreased tight junction protein level was followed by the presence an activation of innate immune responses such as increased Toll-like receptor (TLR) signaling pathways. The altered virome diversity had a positive correlation with serum IL-6, IL-1β, and IFN-γ, intestinal inflammation (IFN-γ), and decreased Brain-Derived Neurotrophic Factor (BDNF), a neurogenesis marker. The co-exposure of Gulf War chemical and antibiotic (for gut sterility) or Gulf War chemical and Ribavirin, an antiviral compound to suppress virus alteration in the gut showed significant improvement in epithelial tight junction protein, decreased intestinal-, systemic-, and neuroinflammation. These results showed that the observed enteric viral dysbiosis could activate enteric viral particle-induced innate immune response in GWI and could be a novel therapeutic target in GWI. |
format | Online Article Text |
id | pubmed-6832151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68321512019-11-20 Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness Seth, Ratanesh K. Maqsood, Rabia Mondal, Ayan Bose, Dipro Kimono, Diana Holland, LaRinda A. Janulewicz Lloyd, Patricia Klimas, Nancy Horner, Ronnie D. Sullivan, Kimberly Lim, Efrem S. Chatterjee, Saurabh Viruses Article Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were altered in GWI. The increased viral richness and alpha diversity correlated positively with gut bacterial dysbiosis and proinflammatory cytokines. Altered virome signature in GWI mice also had a concomitant weakening of intestinal epithelial tight junctions with a significant increase in Claudin-2 protein expression and decrease in ZO1 and Occludin mRNA expression. The altered virome signature in GWI, decreased tight junction protein level was followed by the presence an activation of innate immune responses such as increased Toll-like receptor (TLR) signaling pathways. The altered virome diversity had a positive correlation with serum IL-6, IL-1β, and IFN-γ, intestinal inflammation (IFN-γ), and decreased Brain-Derived Neurotrophic Factor (BDNF), a neurogenesis marker. The co-exposure of Gulf War chemical and antibiotic (for gut sterility) or Gulf War chemical and Ribavirin, an antiviral compound to suppress virus alteration in the gut showed significant improvement in epithelial tight junction protein, decreased intestinal-, systemic-, and neuroinflammation. These results showed that the observed enteric viral dysbiosis could activate enteric viral particle-induced innate immune response in GWI and could be a novel therapeutic target in GWI. MDPI 2019-10-21 /pmc/articles/PMC6832151/ /pubmed/31640184 http://dx.doi.org/10.3390/v11100968 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seth, Ratanesh K. Maqsood, Rabia Mondal, Ayan Bose, Dipro Kimono, Diana Holland, LaRinda A. Janulewicz Lloyd, Patricia Klimas, Nancy Horner, Ronnie D. Sullivan, Kimberly Lim, Efrem S. Chatterjee, Saurabh Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness |
title | Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness |
title_full | Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness |
title_fullStr | Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness |
title_full_unstemmed | Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness |
title_short | Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness |
title_sort | gut dna virome diversity and its association with host bacteria regulate inflammatory phenotype and neuronal immunotoxicity in experimental gulf war illness |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832151/ https://www.ncbi.nlm.nih.gov/pubmed/31640184 http://dx.doi.org/10.3390/v11100968 |
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