Defining Small Intestinal Microbial Landscapes To Improve Therapeutics For Gastrointestinal Disease

定义小肠微生物景观以改善胃肠道疾病的治疗

• 批准号: 10571946
• 负责人: Sean Paul Spencer
• 金额: $ 16.6万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-03 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571946
• 关键词: Abdominal Pain; Antigens; Award; Bacteria; Bile Acids; Biology; Carbohydrates; Characteristics; Chronic Disease; Clinical Data; Clinical Research; Communities; Complement; Complement 2; Data; Deglutition; Development; Development Plans; Devices; Diagnosis; Dietary intake; Disease; Distal; Ecology; Ecosystem; Ensure; Environment; Feces; Frequencies; Gastroenterology; Gastrointestinal Diseases; Gastrointestinal tract structure; Germ-Free; Gnotobiotic; Goals; Health Care Costs; Human; Human Microbiome; Immune; Immune system; Immunity; Immunologic Stimulation; Immunology; In Vitro; Inflammatory; Institution; Intestines; Irritable Bowel Syndrome; Leadership; Libraries; Maps; Medicine; Mentors; Mentorship; Metagenomics; Methods; Microbe; Molecular Genetics; Mus; Outcome; Patients; Phenotype; Phylogenetic Analysis; Physicians; Physiology; Population; Preclinical Testing; Property; Research; Research Personnel; Research Training; Resolution; Resources; Ribosomal RNA; Role; Sampling; Sampling Studies; Science; Scientist; Severities; Site; Small Intestines; Symptoms; Technology; Testing; Therapeutic; Training; Universities; Work; bacterial community; bile acid metabolism; capsule; career; career development; clinical training; colon microbiota; dietary; dysbiosis; effective therapy; experience; gut microbiota; host microbiota; host-microbe interactions; human microbiota; improved; knowledge base; metabolomics; microbial; microbiome research; microbiota; mouse model; novel; novel strategies; novel therapeutic intervention; programs; repository; sample collection; skill acquisition; skills; success; tool; whole genome

Project Summary: Defining Small Intestinal Microbial Landscapes To Improve Therapeutics For Gastrointestinal Disease Disease Relevance: Irritable Bowel Syndrome (IBS) is a chronic disorder characterized by altered bowel function (consistency and/or frequency) in additional to abdominal pain, effecting 7-16% of the US population and associated with an $1 billion of direct health care costs annually. This proposal seeks to better understand IBS and to develop more effective treatments for IBS. Candidate and Career Development Plan: My long-term goal is to become a fully independent physician scientist through leadership of a cutting-edge research program in human microbiota analysis and its association with clinical data complemented using a variety of tools (molecular genetics, metabolomics, gnotobiotic mouse models) to clarify mechanisms of action that will enable development of improved microbiota directed therapeutics for GI disease. Through my clinical training I am poised to become an expert in diagnosing and treating IBS, and through my previous research training am well equipped with the skills to perform high-resolution human and mouse immunology. To fully actualize my career goals of becoming an expert in microbiota-host interactions in IBS I will need to gain skills beyond my current knowledge base. This award will support the needed additional training in microbiota analysis, methods of clinical research, bacterial isolation and culturing, and gnotobiotic mouse models. Research Plan: The overarching research goal of this proposal is to move beyond feces, to define the site-specific microbial ecology of the human small intestine in IBS. We will construct a longitudinal map of intestinal microbiota and metabolites in humans with a swallowed, microbiota sampling capsule device. I have successfully employed this approach in healthy humans and the proposed research will expand sample collection to include IBS patient samples analyzed with microbiota sequencing, novel microbiota-focused metabolomics (Aim 1), and bacterial isolation and functional testing (Aim 2), with complementary studies in gnotobiotic mice (Aim 3) to define fundamental aspects of host- microbe interactions in the small intestine. Mentorship Team: To achieve these Aims, I have assembled a world class mentorship team with expertise in translational human microbiome studies (Justin Sonnenburg, primary mentor), isolation and study of bacteria from the human microbiome (KC Huang, co-mentor), and the treatment and study of IBS (Linda Nguyen, co-mentor). Environment and Institutional Commitment: Stanford University is a world leader in human microbiome studies and treating Gastroenterological(GI) disease. I will have access to mentorship, collaborators, and a breadth of resources that will provide an exceptional training environment. My mentorship team and the leadership within the Stanford Department of Medicine are committed to ensuring my success. The scientific training, skill acquisition, and career development under this award will allow me to become a fully independent physician scientist and leader in the translational microbiota science of GI disease.

项目概要： 定义小肠微生物景观以改善胃肠道疾病的治疗 疾病相关性：肠易激综合症 (IBS) 是一种以肠道改变为特征的慢性疾病 除腹痛外，功能（一致性和/或频率）影响 7-16% 的美国人口 每年涉及 10 亿美元的直接医疗保健费用。该提案旨在更好地理解 IBS 并开发更有效的 IBS 治疗方法。候选人和职业发展计划：我的长期 目标是通过领导尖端研究项目成为一名完全独立的医师科学家 人类微生物群分析及其与临床数据的关联，并使用各种工具进行补充 （分子遗传学、代谢组学、无菌小鼠模型）阐明作用机制，使 开发改进的微生物群定向疗法来治疗胃肠道疾病。通过我的临床训练，我 准备成为诊断和治疗 IBS 的专家，并且通过我之前的研究培训，我表现得很好 具备进行高分辨率人类和小鼠免疫学的技能。充分实现我的职业生涯 成为 IBS 微生物群与宿主相互作用专家的目标 我需要获得超出我目前能力的技能 知识库。该奖项将支持微生物群分析、临床方法等方面所需的额外培训 研究、细菌分离和培养以及无菌小鼠模型。研究计划：总体 该提案的研究目标是超越粪便，定义人类特定地点的微生物生态 IBS 中的小肠。我们将构建人类肠道微生物群和代谢物的纵向图 带有可吞咽的微生物采样胶囊装置。我已经成功地将这种方法应用于健康 人类和拟议的研究将扩大样本收集，以包括用以下方法分析的 IBS 患者样本 微生物群测序、新型微生物群代谢组学（目标 1）以及细菌分离和功能 测试（目标 2），并在限生小鼠中进行补充研究（目标 3），以确定宿主的基本方面 小肠中微生物的相互作用。导师团队：为了实现这些目标，我组建了一个世界 具有转化人类微生物组研究专业知识的班级导师团队（Justin Sonnenburg，小学 导师），从人类微生物组中分离和研究细菌（KC Huang，共同导师），以及治疗 和肠易激综合症（IBS）研究（Linda Nguyen，共同导师）。环境和机构承诺：斯坦福大学 是人类微生物组研究和胃肠病 (GI) 疾病治疗领域的世界领先者。我将有权访问 导师、合作者和广泛的资源将提供卓越的培训环境。 我的导师团队和斯坦福大学医学系的领导层致力于确保 我的成功。该奖项下的科学培训、技能获取和职业发展将使我能够 成为一名完全独立的医师科学家和胃肠道疾病转化微生物科学的领导者。