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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/11/10/968 |
| _version_ | 1811276621474168832 |
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| author | Ratanesh K. Seth Rabia Maqsood Ayan Mondal Dipro Bose Diana Kimono LaRinda A. Holland Patricia Janulewicz Lloyd Nancy Klimas Ronnie D. Horner Kimberly Sullivan Efrem S. Lim Saurabh Chatterjee |
| author_facet | Ratanesh K. Seth Rabia Maqsood Ayan Mondal Dipro Bose Diana Kimono LaRinda A. Holland Patricia Janulewicz Lloyd Nancy Klimas Ronnie D. Horner Kimberly Sullivan Efrem S. Lim Saurabh Chatterjee |
| author_sort | Ratanesh K. Seth |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T00:00:59Z |
| format | Article |
| id | doaj.art-1b3a0771cc0b4ddb9eb7ef089eef81c9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-13T00:00:59Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1b3a0771cc0b4ddb9eb7ef089eef81c92022-12-22T03:11:21ZengMDPI AGViruses1999-49152019-10-01111096810.3390/v11100968v11100968Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War IllnessRatanesh K. Seth0Rabia Maqsood1Ayan Mondal2Dipro Bose3Diana Kimono4LaRinda A. Holland5Patricia Janulewicz Lloyd6Nancy Klimas7Ronnie D. Horner8Kimberly Sullivan9Efrem S. Lim10Saurabh Chatterjee11Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208, USACenter for Fundamental and Applied Microbiomics, The Biodesign Institute, Arizona State University, Tempe, AZ 85281, USAEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208, USAEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208, USAEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208, USACenter for Fundamental and Applied Microbiomics, The Biodesign Institute, Arizona State University, Tempe, AZ 85281, USASchool of Public Health, Boston University, Boston MA 02118, USANOVA Southeastern University, Fort Lauderdale, FL 33314, USADepartment of Health Services Policy and Management, University of South Carolina, Columbia, SC 29208, USASchool of Public Health, Boston University, Boston MA 02118, USACenter for Fundamental and Applied Microbiomics, The Biodesign Institute, Arizona State University, Tempe, AZ 85281, USAEnvironmental Health and Disease Laboratory, Department of Environmental Health Sciences, University of South Carolina, Columbia, SC 29208, USAGulf 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.https://www.mdpi.com/1999-4915/11/10/968gulf war illnessviromemicrobiomenext-generation sequencingintestinal inflammationneuroinflammationribavirinil6 |
| spellingShingle | Ratanesh K. Seth Rabia Maqsood Ayan Mondal Dipro Bose Diana Kimono LaRinda A. Holland Patricia Janulewicz Lloyd Nancy Klimas Ronnie D. Horner Kimberly Sullivan Efrem S. Lim Saurabh Chatterjee Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness Viruses gulf war illness virome microbiome next-generation sequencing intestinal inflammation neuroinflammation ribavirin il6 |
| 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 | gulf war illness virome microbiome next-generation sequencing intestinal inflammation neuroinflammation ribavirin il6 |
| url | https://www.mdpi.com/1999-4915/11/10/968 |
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