The Human Microbiome in Pediatric Abdominal Pain and Intestinal Inflammation

描述：本提案将探索健康儿童和胃肠道疾病儿童肠道微生物群的性质。总体目标是获得一组胃肠道疾病中肠道微生物组的强大知识库，这些疾病代表了儿科胃肠病学中广泛的重要疾病表型。除了对健康儿童和患有肠易激综合征、便秘和炎症性肠病（克罗恩病）的儿童进行详细的临床评估外，还将采用多种策略来导航和了解儿童肠道微生物群的性质。这些策略将包括Sanger测序和基于焦磷酸测序的策略，以了解健康和疾病群体中微生物的详细组成。全基因组散弹枪测序将作为一种探索性策略，全面探索患者宏基因组。基于微阵列的PhyloChip杂交、变性HPLC、实时荧光定量PCR和细菌荧光原位杂交探针将作为互补策略，从分子微生物学的各个角度了解肠道微生物组。第一个假设是，健康的儿童有一个核心的、可识别的微生物群。第二个假设是，人类微生物组中存在疾病特异性特征，这些微生物特征可能与儿科胃肠道疾病表型相关。本研究将探讨青春期前健康儿童和胃肠道疾病儿童的核心和可变人类微生物组的性质。最后，将研究肠道微生物的空间结构和人为因素，以检验不同疾病状态下微生物群落的高阶变化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健康儿童和患有各种肠道疾病的儿童肠道内微生物的了解。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，以及微生物群的特定差异是否可能导致儿童疾病。最终，这个项目的发现可能使医生能够操纵肠道中的微生物，以促进健康，治愈或预防疾病。

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.