Intestinal Microbiome Fructan Metabolism and Symptom Generation in Childhood IBS

儿童 IBS 的肠道微生物组果聚糖代谢和症状产生

• 批准号: 8833276
• 负责人: Bruno Pedro Chumpitazi
• 金额: $ 17.18万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-07 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833276
• 关键词: Abdominal Pain; Acetic Acids; Address; Adult; Affect; Ally; American diet; Applications Grants; Area; Bacteria; Bacteroides; Biochemical Pathway; Bioinformatics; Biological Markers; Child; Childhood; Clinical Research; Colon; Computational Biology; Data; Development Plans; Diagnostic tests; Diet; Dietary Carbohydrates; Dietary Component; Digestive System Disorders; Disease; Double-Blind Method; Economics; Elements; Emotional; Environment; Etiology; Excision; Feces; Fermentation; Food; Fostering; Foundations; Fructans; Fructose; Functional Gastrointestinal Disorders; Funding; Gastroenterologist; Generations; Glucose; Goals; Health; Health Care Costs; Impairment; Ingestion; Institution; Intestines; Irritable Bowel Syndrome; Knowledge; Lactose; Lead; Learning; Medical center; Medicine; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Metagenomics; Methods; Microbiology; Oral; Organism; Pain; Pathway interactions; Patients; Physicians; Pilot Projects; Placebo Control; Placebos; Play; Production; Publications; Quality of life; Randomized; Research; Research Methodology; Research Personnel; Research Project Grants; Research Proposals; Research Training; Resources; Role; School-Age Population; Schools; Scientist; Sequence Analysis; Severities; Staging; Statistical Models; Sucrose; Symptoms; Taxon; Texas; Therapeutic Intervention; Training; Translating; Triad Acrylic Resin; United States; United States National Institutes of Health; Work; base; career; career development; college; design; effective intervention; effective therapy; gastrointestinal; gastrointestinal symptom; gut microbiota; improved; insight; metabolomics; microbial; microbial community; microbiome; non-compliance; novel; open label; patient oriented research; prevent; professional atmosphere; professor; research and development; skills; social

DESCRIPTION (provided by applicant): Dr. Chumpitazi is a board certified pediatric gastroenterologist and tenure track Assistant Professor at Baylor College of Medicine (BCM) with a strong background in clinical research methods and an established commitment to apply these skills to the study of irritable bowel syndrome (IBS). His long term career goal is to become an independent NIH-funded physician scientist proficient in patient oriented research to elucidate the underlying pathobiology in childhood IBS and develop novel and easily applied therapies. His focus is on understanding the interactions between diet and the gut microbiome that induce GI symptoms in childhood IBS. The objective of the current K23 proposal is to obtain training in acquiring, analyzing, and translating data from metagenomic- and metabolomic-based studies related to the gut microbiota to help achieve his long term goal. His short term goals in this proposal are to: 1) Acquire expertise in the study of diet-microbiota interactions by learning methods used to determine microbial community composition, microbial biochemical pathway potential, and microbial metabolite characterization; and 2) Establish an area of independent research by generating a critical mass of data and publications to support a successful R01 NIH grant application. Dr. Chumpitazi's research proposal's objective is to understand the role of the gut microbiome in diet- induced GI symptoms in children with IBS by performing a randomized, double blind, placebo controlled dietary fructan challenge. His hypothesis is that generation of GI symptoms in children with IBS after fructan ingestion is related to gut microbial community composition, its potential for fructan metabolism, and the fermentation products resulting from fructan metabolism. In Aim 1, microbial community composition will be characterized and compared between fructan sensitive (Fsens) and fructan insensitive (Fins) children. In Aim 2, microbial metagenomic signatures related to fructan metabolism will be compared between Fsens and Fins children. Aim 3 will identify potential relationships between products of fructan metabolism and IBS symptoms. These aims support the candidate's career development by providing training in mechanistic aspects of IBS pathobiology as related to diet and gut icrobiota/metagenomic/metabolomic interactions. Additional key elements of the candidate's training plan include: 1) A mentorship and advisory team, which includes internationally recognized, independently funded investigators with expertise in childhood functional GI disorders, bioinformatics, metagenomics, and metabolomics; 2) Advanced coursework in computational biology, microbiology, sequence analysis, and statistical modeling; and 3) Scholarly activities designed to foster independence. Finally, the candidate's research environment is a preeminent academic research institution (Baylor College of Medicine) closely allied with the NIH funded (DK58338) Texas Medical Center Digestive Disease Center which will support the proposed studies and career development plan. This environment will provide a productive and collaborative atmosphere to accomplish the research and training goals. With these ample resources, Dr. Chumpitazi will complete his proposed career development plan and research project in a timely manner and set the stage for his progression to an independently funded physician scientist in patient oriented research.

描述（由申请人提供）：Chumpitazi博士是贝勒医学院（Baylor College of Medicine）的一名委员会认证的儿科胃肠病学家和终身助理教授，在临床研究方法方面具有很强的背景，并致力于将这些技能应用于肠易激综合征（IBS）的研究。他的长期职业目标是成为一名独立的NIH资助的医生科学家，精通以患者为导向的研究，以阐明儿童IBS的潜在病理生物学，并开发新颖且易于应用的疗法。他的重点是了解饮食和肠道微生物组之间的相互作用，这些微生物组在儿童IBS中引起GI症状。目前K23提案的目标是获得获取，分析和翻译与肠道微生物群相关的基于宏基因组和代谢组学的研究数据的培训，以帮助实现他的长期目标。他在这项建议中的短期目标是：1）通过以下方式获得饮食-微生物群相互作用研究的专业知识： 用于确定微生物群落组成，微生物生化途径潜力和微生物代谢产物表征的学习方法; 2）通过生成临界质量的数据和出版物来支持成功的R 01 NIH拨款申请，从而建立独立研究领域。Chumpitazi博士的研究计划的目的是通过进行随机、双盲、安慰剂对照的饮食果聚糖挑战来了解肠道微生物组在IBS儿童饮食诱导的GI症状中的作用。他的假设是，肠易激综合征儿童摄入果聚糖后胃肠道症状的产生与肠道微生物群落组成、果聚糖代谢的潜力以及果聚糖代谢产生的发酵产物有关。在目标1中，将对果聚糖敏感（Fsens）和果聚糖不敏感（Fins）儿童的微生物群落组成进行表征和比较。在目标2中，将在Fsens和Fins儿童之间比较与果聚糖代谢相关的微生物宏基因组特征。目的3将确定果聚糖代谢产物和IBS症状之间的潜在关系。这些目标通过提供与饮食和肠道微生物群/宏基因组/代谢组相互作用相关的IBS病理生物学机制方面的培训来支持候选人的职业发展。候选人培训计划的其他关键要素包括：1）导师和咨询团队，其中包括国际公认的，独立资助的研究人员，具有儿童功能性胃肠道疾病，生物信息学，宏基因组学和代谢组学的专业知识; 2）计算生物学，微生物学，序列分析和统计建模的高级课程;和3）旨在培养独立性的学术活动。最后，候选人的研究环境是一个杰出的学术研究机构（贝勒医学院）与美国国立卫生研究院资助（DK 58338）得克萨斯州医学中心消化疾病中心，这将支持拟议的研究和职业发展计划紧密结盟。这种环境将提供一个富有成效的合作氛围，以实现研究和培训目标。有了这些充足的资源，Chumpitazi博士将及时完成他提出的职业发展计划和研究项目，并为他在以患者为导向的研究中成为一名独立资助的医生科学家奠定基础。