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: 8679136
• 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/8679136
• 关键词: Abdominal Pain; Acetic Acids; Address; Adult; Affect; Ally; American; 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; planetary Atmosphere; prevent; professor; public health relevance; research and development; skills; social; Abdominal Pain; Acetic Acids; Address; Adult; Affect; Ally; American; 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; planetary Atmosphere; prevent; professor; public health relevance; research and development; skills; social

PROJECT SUMMARY 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 microbiota/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.

项目摘要 Chumpitazi博士是董事会认证的小儿胃肠病学家和终身助理助理教授 医学院（BCM）在临床研究方法方面具有强大的背景 承诺将这些技能应用于肠易激综合症（IBS）的研究。他的长期职业目标是 成为一名独立的NIH资助的医师科学家，精通患者的研究以阐明 儿童IBS中的潜在病理生物学，并开发出新颖且易于应用的疗法。他的重点是 了解饮食与肠道微生物组之间诱发胃肠道症状的相互作用 肠易激综合症。当前K23提案的目的是获得获取，分析和翻译数据的培训 来自与肠道菌群有关的宏基因组学和代谢组学的研究，以帮助实现他的长期 目标。他在此提案中的短期目标是：1）在研究饮食 - 微生物研究方面获得专业知识 通过学习方法来确定微生物群落组成，微生物生化的相互作用 途径电位和微生物代谢产物表征； 2）建立一个独立研究领域 通过产生大量的数据和出版物来支持成功的R01 NIH赠款应用程序。 Chumpitazi博士的研究建议的目标是了解肠道微生物组在饮食中的作用 - IBS儿童诱发的胃肠道症状，通过进行随机，双盲，安慰剂控制的饮食 果糖挑战。他的假设是，果糖摄入后IBS儿童的GI症状产生是 与肠道微生物群落组成，果果代谢的潜力和发酵产品有关 由果糖代谢产生。在AIM 1中，微生物群落组成将被表征和比较 在果糖敏感（FSES）和果糖不敏感（FINS）儿童之间。在AIM 2中，微生物宏基因组学 FSES和FINS儿童之间将比较与果糖代谢有关的签名。 AIM 3将确定 果糖代谢产物和IBS症状之间的潜在关系。 这些目标通过在IBS的机械方面提供培训来支持候选人的职业发展 病理生物学与饮食和肠道菌群/元基因组/代谢组相互作用有关。附加键 候选人培训计划的要素包括：1）指导和咨询团队，其中包括 国际认可的独立资助的研究人员具有儿童职能GI专业知识 疾病，生物信息学，宏基因组学和代谢组学； 2）计算中的高级课程 生物学，微生物学，序列分析和统计建模； 3）旨在的学术活动 寄养独立。 最后，候选人的研究环境是一家杰出的学术研究机构（贝勒学院 医学）与NIH资助（DK58338）得克萨斯州医疗中心消化疾病密切相关 中心将支持拟议的研究和职业发展计划。这个环境会 提供一种富有成效的协作氛围，以实现研究和培训目标。与这些 丰富的资源，Chumpitazi博士将完成他拟议的职业发展计划和研究项目 及时的方式，为他的患者的独立医师科学家的发展奠定了基础 定向研究。