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

BCCMA：针对退伍军人部署相关胃肠道和肝脏疾病中的肠道微生物组；

• 批准号: 10588620
• 负责人: NASIA SAFDAR
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588620
• 关键词: Address; Affect; Age; Aging; Award; Bile Acids; Biological Markers; Butyrates; Chronic; Chronic stress; Clinical Trials; Collaborations; Consumption; Critical Illness; Data; Desire for food; Development; Diarrhea; Diet; Dietary Fiber; Disease; Enrollment; Fatigue; Feces; Fermentation; Fiber; Firmicutes; Functional disorder; Funding; Gastrointestinal Diseases; Genes; Goals; Gulf War; Gulf War veteran; Health; Human; Immunity; Incidence; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Intervention; Intervention Studies; Intestinal permeability; Irritable Bowel Syndrome; Knowledge; Liver diseases; Longitudinal Studies; Longitudinal cohort; Measures; Mediating; Metabolism; Metagenomics; Modality; Modeling; Morbidity - disease rate; Mus; Muscle Cramp; Nausea; Neurologic Symptoms; Outcome; Pain; Patients; Persian Gulf; Persian Gulf Syndrome; Play; Post-Traumatic Stress Disorders; Potato; Predisposition; Process; Production; Quality of life; Questionnaires; Randomized; Reporting; Research; Resistance; Respiratory Signs and Symptoms; Risk; Role; Serum; Skin; Source; Starch; Structure; Supplementation; Symptoms; Technology; Therapeutic; Time; Veterans; Volatile Fatty Acids; Vomiting; Work; associated symptom; cohort; combat; comorbidity; comparison control; cost; cytokine; diarrheal disease; effectiveness evaluation; experience; gastrointestinal; gastrointestinal symptom; gut homeostasis; gut inflammation; gut microbiome; gut microbiota; gut-brain axis; humanized mouse; improved; in vivo Model; indexing; inflammatory marker; insight; knowledge base; metagenomic sequencing; microbiome; microbiota; mouse model; novel; novel therapeutics; prebiotics; reduce symptoms; stool sample; transcriptome sequencing; translational impact

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.

据估计，海湾战争疾病（GWI）会影响部署到该部署的70万多名联合部队中的25-32％ 波斯湾作为第一场海湾战争的一部分。 GWI会引起各种各样的疼痛，疲劳，胃肠道，皮肤， 神经系统和呼吸道症状。纵向研究显示 随着时间的流逝症状。因此，迫切需要开发新的治疗方法以减少GWI相关 发病率。 近年来，肠道微生物组在整体健康中的作用一直是重点。肠道微生物组戏剧 在代谢和免疫力中的关键作用。肠道微生物群发酵饮食纤维到产品短链脂肪 酸（SCFA）在宿主能源生产中扮演角色，胃口，被认为扮演重要角色 在肠道轴上。还显示SCFA可保护胃肠道（GI）屏障免受 促炎细胞因子。初步研究表明，肠道微生物组和SCFA可能会发挥作用 在GWI符号中的角色。 我们的总体目标是更好地了解SCFAS和Microbiota在肠道稳态中涉及的角色 在患有GWI的退伍军人中引起肠道功能障碍和炎症 - 开发的下一步至关重要 潜在的治疗目标。我们的中心假设是经历肠道功能障碍的GWI退伍军人 比没有肠道症状的SCFA及其相关的菌群较低的丰度及其相关的菌群 那些在饮食纤维中消耗饮食的人会报告更少的胃肠道符号。我们计划评估这一点 假设使用现有的36名GWI退伍军人和33个对照的纵向队列以及 招募有48名具有胃肠道症状的48名GWI退伍军人的队列，以研究以下特定目的： 目标1：评估GWI，肠道渗透性与肠道功能潜力之间的关系 使用和不使用GWI的退伍军人中的微生物组，使用以前的整个元基因组测序 收集的粪便标本。 目标2：检查测量的低度炎症与存在的关系 短链脂肪酸和其他使用肠道元基因组数据鉴定的预测代谢产物 与没有GWI的退伍军人使用先前存在的血清和粪便样品相比。 目标3：实施抵抗马铃薯淀粉干预以减轻与之相关的症状 GWI并改善退伍军人的生活质量。 拟议的研究是我们收到的试点资金的直接延续，以评估 与GWI的退伍军人。通过拟议的研究，我们将通过GWI知识库建立 对代谢产物的作用和与肠道稳态有关的微生物的作用有更好的了解 引起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，低风险的饮食 减轻与GWI相关的符号，尤其是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，而且还可以 还可能有助于开发针对其他战斗和非战斗与功能性GI疾病的治疗方法。