Quantitative measurements of intestinal metabolites in healthy and IBS children

描述（由申请人提供）：在健康人体中，有数十亿细菌定植在肠道中。这种肠道微生物群是一种复杂的微生物群落，在炎症性肠病、肠易激综合征（IBS）和结肠癌等多种肠道疾病中发挥作用。其中，IBS是儿童中常见的疾病，影响高达25%的学龄儿童和青少年。然而，我们对IBS和其他疾病中微生物群组成及其代谢活动产物的变化的了解是不完整的。缺乏对健康和患病个体之间微生物群差异的定量测量。与此同时，有关这个复杂群落代谢活动的信息现在才开始出现。此外，虽然儿童和成人都患有这些疾病，但以前的大多数研究都是在成人中进行的。 我们的长期目标是研究人类肠道疾病中的微生物群动力学和代谢活动。在本申请中，我们试图通过测量来自这些患者的粪便样本中的代谢物水平来扩展我们正在进行的健康儿童和IBS儿童的微生物群组成的分析。将通过1H NMR光谱法测量代谢物特征，并将使用代谢组学方法识别样品之间的差异。将使用多种统计和聚类方法分析代谢物数据，并将代谢物水平与细菌丰度数据和临床参数相关联。粪便代谢物水平的定量测量有望提供微生物群落结构与宿主肠道状态之间的联系，并且它们可以提供关于IBS发展机制的新假设。 公共卫生相关性：肠道微生物群是一个复杂的微生物群落，被认为在几种肠道疾病如肠易激综合征（IBS）中发挥作用。虽然有证据表明IBS患者的肠道生物群与健康个体不同，但我们仍然缺乏对IBS中特定微生物群变化的了解。与此同时，关于这个复杂群体的代谢活动的信息现在才开始出现，尽管有证据表明肠道细菌发酵终产物水平的失衡可能导致慢性疾病，如IBS和炎症性肠病。 本申请中提出的研究将通过测量这些患者粪便样本中的代谢物水平，寻求扩大我们正在进行的健康儿童和IBS儿童微生物群组成分析。相同粪便样品中微生物群组成和代谢物水平的比较预期揭示特定内腔代谢物的产生或消耗与特定细菌物种和组的存在或相对丰度之间的推定关联。预计拟议的实验和分析将对肠道环境的“工作”产生新的见解，开发和测试肠道疾病的新诊断能力，并指导这种疾病的新治疗策略的开发。

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.