The Human Microbiome in Pediatric Abdominal Pain and Intestinal Inflammation

小儿腹痛和肠道炎症中的人类微生物组

基本信息

批准号：
8306346
负责人：
James Versalovic
金额：
$ 91.89万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-24 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306346
关键词：
Abdominal Pain Adolescent Adult Affect Architecture Biological Markers Breath Tests Child Childhood Clinical assessments Constipation Crohn&apos s disease DNA Microarray Chip DNA Sequence Data Diarrhea Dideoxy Chain Termination DNA Sequencing Disease Disease remission Ecology Ecosystem Fluorescent in Situ Hybridization Functional disorder Gases Gastroenterology Gastrointestinal Diseases Gastrointestinal tract structure Genetic Genetic Determinism Genome Goals Health High Pressure Liquid Chromatography Human Human Characteristics Human Genetics Human Microbiome Immune Response Genes Immune response Immunologics Individual Inflammatory Bowel Diseases Inflammatory disease of the intestine Integration Host Factors Intestinal Diseases Intestinal Motility Intestines Irritable Bowel Syndrome Leukocyte L1 Antigen Complex Leukocytes Metagenomics Microbe Microbiology Molecular Monitor Nature Organism Patients Pattern Perception Phase Physicians Physiology Population Production Recombinant DNA Recurrence Relative (related person)Ribosomal RNA Sampling Scientist Small Intestines Specimen Time Tissues Variant Visceral pain Whole-Genome Shotgun Sequencing base boys commensal microbes density disease phenotype gastrointestinal girls knowledge base metagenome microbial microbial community microbiome microorganism prevent

项目摘要

DESCRIPTION: This proposal will explore the nature of the human intestinal microbiome in healthy children and children with gastrointestinal (GI) disorders. The overall goal is to obtain a robust knowledge-base of the intestinal microbiome in a set of GI disorders that represent a broad spectrum of important disease phenotypes in pediatric gastroenterology. In addition to the detailed clinical assessment of healthy children and children with irritable bowel syndrome, constipation, and inflammatory bowel disease (Crohn disease), multiple strategies will be deployed to navigate and understand the nature of the intestinal microbiome in childhood. These strategies will include Sanger sequencing and pyrosequencing-based strategies to understand the detailed composition of microbes in healthy and disease groups. Whole genome shotgun sequencing will be used as an exploratory strategy to explore metagenomes in patients in a comprehensive manner. Microarray-based hybridization with the PhyloChip, denaturing HPLC, quantitative real-time PCR, and bacterial fluorescence in situ hybridization probes will be applied as complementary strategies to gain an understanding of the intestinal microbiome from various perspectives in molecular microbiology. The first hypothesis is that healthy children have a core, identifiable microbiome. The second hypothesis is that disease-specific signatures in the human microbiome are present, and these microbial signatures may be correlated with pediatric gastrointestinal disease phenotypes. This proposal will explore the nature of core and variable human microbiomes in pre-adolescent healthy children and children with GI disorders. Finally, spatial architecture of intestinal microbes and human factors will be studied in order to examine higher-order alterations in microbial communities in different disease states and the relative contributions of human immune response genes. PUBLIC HEALTH RELEVANCE: This project will increase our understanding of the microbes that reside in the intestines of healthy children and children with various intestinal disorders. The findings from this project will enable scientists to determine the nature of beneficial microbial populations in intestines of healthy children, and whether specific differences in groups of microbes may contribute to diseases in children. Ultimately, the discoveries from this project may allow physicians to manipulate microbes in the intestine in order to promote health and cure or prevent disease.

描述：该提案将探讨健康儿童和胃肠道（GI）疾病儿童中人类肠道微生物组的性质。总体目标是在一组胃肠道疾病中获得肠道微生物组的鲁棒知识基础，这些疾病代表了小儿胃肠病学中重要的疾病表型。除了对健康儿童和肠易激综合征，便秘和炎症性肠病（克罗恩病）的详细临床评估外，还将部署多种策略，以导航和了解儿童肠道微生物的性质。这些策略将包括桑格测序和基于焦磷酸测序的策略，以了解健康和疾病组中微生物的详细组成。整个基因组shot弹枪测序将用作探索性策略，以全面的方式探索患者的宏基因组。基于微阵列的杂交与植物，变性HPLC，定量实时PCR和细菌荧光原位杂交探针将被用作互补策略，以在分子微生物学中从各种角度了解肠道微生物组的理解。第一个假设是健康的孩子具有可识别的核心微生物组。第二个假设是存在人类微生物组中的疾病特异性特异性特异性特异性特异性，这些微生物特征可能与小儿胃肠道疾病表型相关。该提案将探讨青春期前健康儿童和胃肠病疾病儿童中核心和可变人类微生物的性质。最后，将研究肠道微生物和人为因素的空间结构，以检查不同疾病状态中微生物群落的高阶改变以及人类免疫反应基因的相对贡献。公共卫生相关性：该项目将增加我们对存在于各种肠道疾病的健康儿童和儿童的肠道中的微生物的理解。该项目的发现将使科学家能够确定健康儿童肠道中有益微生物种群的性质，以及微生物组的特定差异是否可能导致儿童疾病。最终，该项目的发现可能会使医生可以操纵肠中的微生物，以促进健康，治愈或预防疾病。