BCCMA: Targeting Gut-Microbiome in Veterans Deployment related Gastrointestinal and Liver diseases; CMA5- Functional metagenomics in GWI-related gut dysfunction

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Gulf War Illness (GWI) is estimated to affect 25-32% of the over 700,000 coalition troops deployed to the Persian Gulf as part of the First Gulf War. GWI causes a wide array of pain, fatigue, gastrointestinal, skin, neurologic, and respiratory symptoms. Longitudinal studies have shown little to no overall improvement in symptoms over time. There is thus a critical need to development new treatments to reduce GWI-associated morbidity. The role of the gut microbiome in overall health has been a focus in recent years. The gut microbiome plays critical roles in metabolism and immunity. Gut microbiota ferment dietary fibers to product short-chain fatty acids (SCFAs), which play roles in host energy production, appetite, and are thought to play important roles in the gut-brain axis. SCFAs have also been shown to protect the gastrointestinal (GI) barrier from proinflammatory cytokines. Preliminary research suggests that the gut microbiome and SCFAs may play a role in GWI symptoms. Our overall goal is to better understand the role that SCFAs and the microbiota involved in gut homeostasis have in causing gut dysfunction and inflammation in Veterans with GWI – the critical next step in developing potential treatment targets. Our central hypothesis is GWI Veterans experiencing gut dysfunction will have lower abundances of SCFAs and their associated microbiota than those without gut symptoms and that those consuming diets higher in dietary fiber will report fewer GI symptoms. We plan to evaluate this hypothesis using both an existing, longitudinal cohort of 36 GWI Veterans and 33 controls as well as enrolling a new cohort of 48 GWI Veterans with GI symptoms to investigate the following specific aims: Aim 1: To assess the relationship between GWI, gut permeability, and the functional potential of the gut microbiome in Veterans with and without GWI using whole metagenome sequencing of previously collected stool specimens. Aim 2: To examine the relationship between low-grade inflammation measured and the presence of short-chain fatty acids and other predicted metabolites identified using the gut metagenomic data in Veterans with GWI compared to those without GWI using pre-existing serum and stool samples. Aim 3: Implementation of a resistant potato starch intervention to alleviate symptoms associated with GWI and improve Veterans’ quality of life. The proposed research is a direct continuation of pilot funding we received to assess the microbiomes of Veterans with GWI. Through the proposed research, we will build on the GWI knowledge base through developing a better understanding of the role of metabolites and the microbiota involved in gut homeostasis in causing gut dysfunction and inflammation in GWI Veterans – the critical next step in developing potential treatment targets. We will also conduct an intervention study to evaluate the role of a low-cost, low-risk dietary fiber intervention (resistant potato starch prebiotic) in alleviating GWI-related symptoms, particularly GI symptoms. The work proposed here has the potential to not only improve the lives of Veterans with GWI, but may also help develop treatments for other combat and non-combat related functional GI diseases.