Intestinal Microbiome Fructan Metabolism and Symptom Generation in Childhood IBS

项目总结

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.