Pharmacology, Toxicology and Environmental Health | Open Access Articles

Obesity Worsens Gulf War Illness Symptom Persistence Pathology By Linking Altered Gut Microbiome Species To Long-Term Gastrointestinal, Hepatic, And Neuronal Inflammation In A Mouse Model, Dipro Bose, Punnag Saha, Ayan Mondal, Brian Fanelli, Ratanesh K. Seth, Patricia Janulewicz, Kimberly Sullivan, Stephen Lasley, Ronnie Horner, Rita R. Colwell, Ashok K. Shetty, Nancy Klimas, Saurabh Chatterjee

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Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese …

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Tlr Antagonism By Sparstolonin B Alters Microbial Signature And Modulates Gastrointestinal And Neuronal Inflammation In Gulf War Illness Preclinical Model, Dipro Bose, Ayan Mondal, Punnag Saha, Diana Kimono, Sutapa Sarkar, Ratanesh K. Seth, Patricia Janulewicz, Kimberly Sullivan, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

The 1991 Persian Gulf War veterans presented a myriad of symptoms that ranged from chronic pain, fatigue, gastrointestinal disturbances, and cognitive deficits. Currently, no therapeutic regimen exists to treat the plethora of chronic symptoms though newer pharmacological targets such as microbiome have been identified recently. Toll-like receptor 4 (TLR4) antagonism in systemic inflammatory diseases have been tried before with limited success, but strategies with broad-spectrum TLR4 antagonists and their ability to modulate the host-microbiome have been elusive. Using a mouse model of Gulf War Illness, we show that a nutraceutical, derived from a Chinese herb Sparstolonin B (SsnB) presented a …

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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, Ratanesh K. Seth, Rabia Maqsood, Ayan Mondal, Dipro Bose, Diana Kimono, Larinda A. Holland, Patricia Janulewicz Lloyd, Nancy Klimas, Ronnie Horner, Kimberly Sullivan, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

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 …

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