The Human Microbiome in Pediatric Abdominal Pain and Intestinal Inflammation

产品说明：该提案将探索健康儿童和胃肠道（GI）疾病儿童的人类肠道微生物组的性质。总体目标是获得一组GI疾病中肠道微生物组的强大知识库，这些GI疾病代表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，还将部署多种策略来导航和了解儿童肠道微生物组的性质。这些策略将包括基于桑格测序和焦磷酸测序的策略，以了解健康和疾病组中微生物的详细组成。全基因组鸟枪测序将作为一种探索性策略，以全面的方式探索患者的宏基因组。基于微阵列的杂交与PhyloChip，变性HPLC，定量实时PCR和细菌荧光原位杂交探针将被应用作为互补策略，以获得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、可识别的微生物组。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。该提案将探索青春期前健康儿童和GI疾病儿童中核心和可变人体微生物组的性质。最后，将研究肠道微生物和人为因素的空间结构，以研究不同疾病状态下微生物群落的高阶变化和人类免疫应答基因的相对贡献。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，该项目的发现可能使医生能够操纵肠道中的微生物，以促进健康，治疗或预防疾病。

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.