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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
Project #
5UH3DK083990-04
Application #
8306346
Study Section
Special Emphasis Panel (ZRG1-IDM-A (52))
Program Officer
Karp, Robert W
Project Start
2009-06-24
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$918,937
Indirect Cost
$373,881
Name
Baylor College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Davidovics, Zev H; Carter, Beth A; Luna, Ruth Ann et al. (2016) The Fecal Microbiome in Pediatric Patients With Short Bowel Syndrome. JPEN J Parenter Enteral Nutr 40:1106-1113
Chehoud, Christel; Dryga, Anatoly; Hwang, Young et al. (2016) Transfer of Viral Communities between Human Individuals during Fecal Microbiota Transplantation. MBio 7:e00322
Hollister, Emily B; Riehle, Kevin; Luna, Ruth Ann et al. (2015) Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome 3:36
Chumpitazi, B P; Cope, J L; Hollister, E B et al. (2015) Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome. Aliment Pharmacol Ther 42:418-27
Kellermayer, Richard; Nagy-Szakal, Dorottya; Harris, R Alan et al. (2015) Serial fecal microbiota transplantation alters mucosal gene expression in pediatric ulcerative colitis. Am J Gastroenterol 110:604-6
Gao, Chunxu; Major, Angela; Rendon, David et al. (2015) Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri. MBio 6:e01358-15
Hollister, Emily B; Gao, Chunxu; Versalovic, James (2014) Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology 146:1449-58
Boonma, Prapaporn; Spinler, Jennifer K; Venable, Susan F et al. (2014) Lactobacillus rhamnosus L34 and Lactobacillus casei L39 suppress Clostridium difficile-induced IL-8 production by colonic epithelial cells. BMC Microbiol 14:177
Chumpitazi, Bruno P; Hollister, Emily B; Oezguen, Numan et al. (2014) Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome. Gut Microbes 5:165-75
Hemarajata, P; Spinler, J K; Balderas, M A et al. (2014) Identification of a proton-chloride antiporter (EriC) by Himar1 transposon mutagenesis in Lactobacillus reuteri and its role in histamine production. Antonie Van Leeuwenhoek 105:579-92

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