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.

海湾战争疾病(GWI)估计影响到部署在阿富汗的70多万联军中的25%-32% 波斯湾是第一次海湾战争的一部分。严重创伤会引起广泛的疼痛、疲劳、胃肠道、皮肤、 神经学和呼吸系统症状。纵向研究表明，总体上几乎没有改善 随着时间的推移会出现症状。因此，迫切需要开发新的治疗方法来减少与GWI相关的 发病率。 近年来，肠道微生物群在整体健康中的作用一直是人们关注的焦点。肠道微生物群发挥作用 在新陈代谢和免疫中的关键作用。肠道微生物区系发酵膳食纤维生产短链脂肪 酸(SCFA)，它在宿主的能量生产、食欲中发挥作用，并被认为发挥着重要作用 在肠轴-脑轴上。单链脂肪酸还被证明可以保护胃肠道(GI)屏障免受 促炎细胞因子。初步研究表明，肠道微生物群和单链脂肪酸可能在 在GWI症状中的作用。 我们的总体目标是更好地了解单链脂肪酸和微生物区系在肠道动态平衡中的作用。 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。我们的中心假设是经历过肠道功能障碍的退伍军人会有 与没有肠道症状的人相比，SCFAs及其相关微生物群的丰度更低， 那些饮食中膳食纤维含量较高的人报告的胃肠道症状会较少。我们计划对此进行评估 假设使用了36名退伍军人和33名对照的现有纵向队列，以及 招募48名有胃肠道症状的退伍军人作为新的队列，以调查以下具体目标： 目的1：评估GWI、肠道通透性和肠道功能潜能之间的关系 用以前的全基因组测序方法研究有无GWI的退伍军人的微生物组 收集了粪便样本。 目的2：检查检测到的低度炎症与存在 短链脂肪酸和其他预测的代谢物使用肠道元基因组数据在 使用预先存在的血清和粪便样本比较有GWI的退伍军人和没有GWI的退伍军人。 目标3：实施抗药性马铃薯淀粉干预措施，以缓解与 提高退伍军人的生活质量。 这项拟议的研究是我们收到的试验资金的直接延续，以评估 有GWI的退伍军人。通过拟议的研究，我们将通过以下方式建立GWI知识库 更好地了解代谢物和微生物区系在肠道内稳态中的作用 导致退伍军人肠道功能障碍和炎症--开发潜力的关键下一步 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素)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退伍军人的生活，而且 可能还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。