DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Posted November 20, 2019

Dr. Saurabh Chatterjee, University of South Carolina

Dr. Saurabh Chatterjee
Dr. Saurabh Chatterjee
Dr. Ratanesh Seth
Dr. Ratanesh Seth

In a recent publication in the journal Viruses, a team of researchers including Drs. Saurabh Chatterjee and Ratanesh Seth of the University of South Carolina demonstrated that exposure to Gulf War (GW) chemicals led to altered bacterial and viral populations, especially bacteriophages, in the gut in a mouse model of GWI. This increased viral richness and diversity contributed to gut bacterial dysbiosis and activated an innate immune response that was associated with intestinal proinflammatory response and neuroinflammation. Interestingly, administration of an antiviral drug (Ribavarin) administered for partial depletion of gut virome in GW-exposed mice decreased viral richness and diversity compared to untreated GWI mice, making the mice more like unexposed controls. Similarly, antibiotic treatment in GW-exposed mice (Enrofloxacin and Neomycin) led to decreased bacterial diversity, to levels not significantly different from unexposed control mice. Both treatments also rescued increased systemic inflammation, a known contributor to GWI, demonstrated in GW-exposed mice. Most importantly, the study demonstrated that an anti-viral or antibiotic intervention improved neuroinflammation in GWI.

To further develop these findings and pursue a potential treatment strategy, the DoD Gulf War Illness Research Program (GWIRP) awarded Dr. Chatterjee an Investigator-Initiated Focused Research Award in 2018 to continue to explore the role of a gut microbiome-brain connection in the persistence of symptoms in GWI and to better understand the link between inflammation resulting from altered gut bacteria and its role in disease development. To do this, the team will again use a mouse model of GWI, but will also look at blood samples from a repository of samples from ill Gulf War veterans. Finally, the project will test a potential treatment with butyric acid, a short chain fatty acid that is already approved for human use, in the mouse model of GWI. It is hoped that this novel treatment strategy along with combination therapy of antivirals and nutraceuticals, if successful, will be able to be widely implemented in a short period of time to alleviate the symptoms suffered by those with GWI and improve their quality of life.

Publication:
Seth RK, et al. 2019. Gut DNA Virome Diversity and Its Association with Host Bacteria Regulate Inflammatory Phenotype and Neuronal Immunotoxicity in Experimental Gulf War Illness. Viruses 2019, 11(10), 968; https://doi.org/10.3390/v11100968

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Last updated Tuesday, November 19, 2019