Quantitative measurements of intestinal metabolites in healthy and IBS children

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DESCRIPTION (provided by applicant): In the healthy human, there are billions of bacteria colonizing the intestine. This intestinal microbiota is a complex community of microorganisms that plays a role in several intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome (IBS), and colon cancer. Among these, IBS is a common disorder in children, affecting up to 25% of school-age children and adolescents. However, our knowledge of the changes in microbiota composition and products of their metabolic activity in IBS and other diseases is incomplete. There is a lack of quantitative measurements of microbiota differences between healthy and ill individuals. At the same time, information on the metabolic activity of this complex community is only now starting to appear. Moreover, while both children and adults suffer from these disorders, the majority of previous studies were carried out in adults. Our long-term goal is to study microbiota dynamics and metabolic activities in human intestinal disorders. In this application we seek to expand our ongoing analysis of microbiota composition in healthy children and children with IBS by measuring metabolite levels in fecal samples from these patients. Metabolite signatures will be measured by 1H NMR spectroscopy and metabolomics approach will be used to identify differences among samples. Multiple statistical and clustering approaches will be utilized to analyze the metabolite data and to correlate the metabolite levels to the bacterial abundance data and clinical parameters. The quantitative measurements of fecal metabolite levels are expected to provide a link between microbiota community structure and the status of the host intestine, and they can offer new hypotheses on the mechanism(s) of IBS development. PUBLIC HEALTH RELEVANCE: Intestinal microbiota is a complex community of microorganisms that is believed to play a role in several intestinal diseases such as irritable bowel syndrome (IBS). Though there is evidence that the gut biota of IBS patients differs from that of the healthy individuals, we still lack the understanding of specific microbiota changes in IBS. At the same time, information on the metabolic activity of this complex community is only now starting to appear, despite the evidence that misbalance in the levels of end-products of intestinal bacterial fermentation can lead to chronic disorders such as IBS and inflammatory bowel disease. The research proposed in this application will seek to expand our ongoing analysis of microbiota composition in healthy children and children with IBS by measuring metabolite levels in fecal samples from these patients. The comparisons of microbiota composition and metabolite levels in the same fecal samples are anticipated to reveal putative associations between production or consumption of particular lumenal metabolites and the presence or relative abundance of particular bacterial species and groups. The proposed experiments and analyses are expected to yield new insights into the 'workings' of the intestinal environment, develop and test new diagnostic capabilities for intestinal diseases, and guide the development of new therapeutic strategies for this disorder.