Understanding Gut-Microbiome Links to Gulf War Illness Persistence and Development of Gut Dysbiosis-Targeted Therapy
Abstract
The 1990-1991 first Gulf War (GW) that was comprised of the “Operation Desert Storm” and “Operation Desert Shield” saw the deployment of more than 700,000 of US troops. In spite of a long span of 25 years since the war ended, Veterans continue to suffer from a series of chronic multi-symptom illness that consist of chronic fatigue, post-traumatic stress, chronic pain, neurological abnormalities, gastrointestinal (GI) disturbances, and metabolic alterations. It has been perceived that the symptom persistence of Gulf War Illness (GWI) is a major challenge at the clinics. Though significant understanding has been gained from the preclinical and clinical studies, we do not have a definite therapeutic regimen for these symptoms. Our recently published study sheds light on a novel mechanism of GWI pathogenesis and symptom persistence. We found that the gut microbiome alterations due to GW chemical exposure causes GI disturbances and is strongly linked to neuroinflammation. So, the present project on GWI aims to explore (1) role of gut microbiome-brain axis in symptom persistence, (2) understand the causal link between the soluble mediators of inflammation as a result of gut microbiome alteration and their role in systemic disease development in GW mouse models and Veterans, and (3) find effective treatment with butyric acid, a short chain fatty acid that helps the Veterans in the present situation alleviate their symptoms and improve their quality of life. With advancement of modern medicine and molecular research in life sciences, we have started to understand a new area of our human physiological system. Gut microbiome or the immense numbers of diverse bacteria that reside in our GI tract have been found to be associated with many diseases. Most often these bacteria are involved in regulating vital processes of the physiological system while alterations lead to disease. It is high time that we study the diverse bacterial behavior to unravel the cause of the GWI that continues to plague our Veterans. Interestingly, altered gut microbial population is increasingly being recognized to influence neurological behavior and vice versa. Based on the above scientific rationale, the present proposal tests the hypothesis that GW chemical exposure in rodent models and GW Veteran cohorts cause oxidative stress-induced change in gut bacterial diversity resulting in gut leaching, systemic endotoxemia, GI inflammation, insulin resistance, metabolic complications, and neural inflammation. The hypothesis will be tested by two specific research aims. We will use an established rodent model of GWI with some modifications. In Aim 1, we will study the gut microbiome alterations in mice and GW Veteran cohorts and their link to GI, metabolic, and neural complications. In Aim 3, we will test the effect of butyric acid, a short chain fatty acid (SCFA), a Food and Drug Administration (FDA)-approved, widely popular drug used for GI complications on the microbiome-related changes in pathophysiology of GWI. The project, if successful, will have tremendous translational impact by finding a novel mechanistic pathway for GWI and a novel treatment strategy that can be implemented immediately. Moreover, the identification of microbial alterations in GW Veterans and the effectiveness of an FDA-approved probiotic therapeutic strategy will pave the way for a personalized medicine approach that is both novel and timely.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810374
Entities
People
- Saurabh Chatterjee
Organizations
- United States Army
- University of South Carolina