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.

项目摘要： 定义小肠道微生物景观以改善胃肠道疾病的治疗剂 疾病相关性：肠易激综合征（IBS）是一种慢性疾病，其特征是肠子改变 除腹痛外，功能（一致性和/或频率），影响美国人口的7-16％ 并与每年有10亿美元的直接医疗保健费用相关。该建议试图更好地理解 IBS并为IBS开发更有效的治疗方法。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计划成为完全独立的医师科学家 在人类微生物群分析及其与使用多种工具补充的临床数据的关联 （分子遗传学，代谢组学，gnotobiotic小鼠模型），以澄清将启用的作用机制 开发改进的微生物群指导胃病的治疗剂。通过我的临床培训我是 准备成为诊断和治疗IB的专家，并且通过我以前的研究培训 配备了执行高分辨率人和小鼠免疫学的技能。充分实现我的职业 成为IBS中微生物群互动专家的目标，我将需要获得超越当前的技能 知识库。该奖项将支持微生物群分析中所需的额外培训，临床方法 研究，细菌分离和培养以及gnotobiotic小鼠模型。研究计划：总体 该建议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。我们将在人类中构建肠道菌群和代谢物的纵向图 带有吞咽的菌群采样胶囊设备。我已经成功地采用了这种方法 人类和拟议的研究将扩大样本收集到包括对IBS的患者样本进行分析 微生物群测序，新型以微生物群为中心的代谢组学（AIM 1）以及细菌分离和功能性 测试（AIM 2），对gnotobiotic小鼠进行互补研究（AIM 3），以定义宿主的基本方面 小肠中的微生物相互作用。指导团队：为了实现这些目标，我汇集了一个世界 班级指导团队具有翻译人类微生物组研究专业知识（Justin Sonnenburg，主要 导师），从人类微生物组（KC Huang，Co-Insor）和治疗的细菌分离和研究 和IBS的研究（Linda Nguyen，Co-Insor）。环境和机构承诺：斯坦福大学 是人类微生物组研究和治疗胃肠病学（GI）疾病的世界领导者。我将可以访问 指导，合作者以及将提供卓越培训环境的广泛资源。 我的指导团队和斯坦福大学医学系内的领导人致力于确保 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 成为完全独立的医师科学家和胃肠道疾病转化菌群科学的领导者。