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

据估计，海湾战争病（GWI）影响了部署在海湾地区的70多万联军部队中的25-32%。 波斯湾是第一次海湾战争的一部分GWI引起广泛的疼痛，疲劳，胃肠道，皮肤， 神经系统和呼吸系统症状纵向研究显示， 症状随着时间的推移。因此，迫切需要开发新的治疗方法以减少GWI相关的 发病率 近年来，肠道微生物组在整体健康中的作用一直是一个焦点。肠道微生物组扮演着 在新陈代谢和免疫中起重要作用。肠道微生物群发酵膳食纤维产生短链脂肪酸 酸性脂肪酸（SCFAs），在宿主的能量产生、食欲等方面发挥作用，被认为发挥着重要作用 在肠脑轴上。SCFA还被证明可以保护胃肠道（GI）屏障， 促炎细胞因子初步研究表明，肠道微生物组和SCFAs可能发挥作用， 在GWI症状中的作用。 我们的总体目标是更好地了解SCFAs和微生物群在肠道稳态中的作用 在GWI退伍军人中引起肠道功能障碍和炎症-发展的关键下一步 潜在的治疗目标我们的中心假设是GWI退伍军人经历肠道功能障碍将有 SCFAs及其相关微生物群的丰度低于没有肠道症状的人， 那些食用高纤维饮食的人将报告更少的GI症状。我们计划对此进行评估 假设使用现有的，纵向队列的36个GWI退伍军人和33个对照，以及 招募了一个新的48名具有GI症状的GWI退伍军人队列，以研究以下具体目标： 目的1：探讨胃肠道指数（GWI）、肠道通透性与肠道功能的关系 使用先前的全宏基因组测序，在有和没有GWI的退伍军人中的微生物组 收集粪便标本。 目的2：检查测量的低度炎症与存在的 使用肠道宏基因组数据鉴定的短链脂肪酸和其他预测代谢物 使用预先存在的血清和粪便样本将GWI退伍军人与无GWI的退伍军人进行比较。 目标3：实施抗性马铃薯淀粉干预，以缓解与 GWI和提高退伍军人的生活质量。 拟议的研究是我们收到的用于评估微生物组的试点资金的直接延续。 退伍军人与GWI。通过拟议的研究，我们将通过以下方式建立GWI知识库： 更好地理解代谢物和参与肠道稳态的微生物群的作用， 导致GWI退伍军人的肠道功能障碍和炎症-发展潜力的关键下一步 治疗目标。我们还将进行一项干预研究，以评估低成本、低风险饮食的作用。 纤维干预（抗性马铃薯淀粉益生元）缓解GWI相关症状，特别是GI 症状这里提出的工作不仅有可能改善GWI退伍军人的生活， 还可能有助于开发其他战斗和非战斗相关功能性胃肠道疾病的治疗方法。

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.