Using Affymetrix Microflora array to study microflora composition in children wit

描述(申请人提供)：在健康人体内，有数十亿种细菌在肠道中定植。这种肠道微生物群是一个复杂的微生物群落，在几种肠道疾病中发挥作用，如炎症性肠病、肠易激综合征(IBS)和结肠癌。其中，IBS是一种常见的儿童疾病，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区系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区系差异的定量测量。此外，虽然儿童和成年人都患有这些疾病，但以前的大多数研究都是在成年人身上进行的。我们对肠道疾病期间微生物区系动态的缺乏了解阻碍了新的和令人兴奋的药物的开发和评估，如益生菌。我们的长期目标是研究肠道疾病期间的微生物区系动态，并评估益生菌作为此类疾病的治疗选择的使用。在这个项目中，我们将使用我们专门设计的定制微阵列来研究人类胃肠道的微生物群结构，我们将定量比较健康儿童和IBS儿童粪便中的微生物群组成；我们将测试使用益生菌VSL#3治疗IBS儿童是否会导致微生物群组成的特定变化，以反映健康儿童的微生物群组成。在益生菌治疗开始之前对肠道疾病患者进行微生物区系筛查的可能性可以提供有关微生物区系状况的有用信息，这将有助于选择适当的益生菌治疗。同时，评估益生菌处理期间微生物区系变化的能力将提供有关益生菌对微生物群落影响的直接信息。 与公共卫生相关：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中发挥作用，如肠易激综合征(IBS)。虽然有证据表明IBS患者的肠道菌群与健康人不同，但我们仍然缺乏对IBS特定微生物区系变化的了解。这些知识的缺乏导致了解释IBS治疗结果的困难，特别是涉及益生菌的治疗结果。这项申请中提出的研究将描述健康儿童和接受益生菌治疗的IBS儿童的微生物群组成。对这些儿童之间的微生物区系组成的比较将：1)提供有关儿童IBS期间微生物区系状况的信息以及益生菌治疗后的变化；2)加快评估和开发新的治疗方案，如旨在恢复正常微生物区系组成的益生菌制剂；以及3)为进一步研究益生菌对微生物区系的影响奠定必要的微生物区系组成知识基础。

DESCRIPTION (provided by applicant): In the healthy human, there are billions of bacteria colonizing the intestine. This intestinal microflora 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 microflora in IBS and other diseases is incomplete. There is a lack of quantitative measurements of microflora differences between healthy and ill individuals. Moreover, while both children and adults suffer from these disorders, the majority of previous studies were carried out in adults. Our lack of understanding of microflora dynamics during intestinal diseases retards the development and evaluation of new and exciting medicines, such as probiotics. Our long-term goal is to study microflora dynamics during intestinal disorders and to assess the use of probiotics as treatment options for such illnesses. In this project, using a custom microarray specifically designed by us to study microflora structure in the human gastrointestinal tract, we will quantitatively compare the microflora composition in the feces of healthy children with that in children with IBS; and we will test if the use of probiotic VSL#3 to treat children suffering from IBS will lead to specific changes in microflora composition to mirror that of healthy children. The potential for screening of microflora in patients suffering from intestinal disorders before the onset of probiotic treatment can provide useful information on microflora status that would help in the choice of an appropriate probiotic therapy. At the same time, the ability to assess changes in microflora during probiotic treatment will provide direct information on the effect of probiotics on the microflora community. PUBLIC HEALTH RELEVANCE: Intestinal microflora 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 flora of IBS patients differs from that of the healthy individuals, we still lack the understanding of specific microflora changes in IBS. The paucity of such knowledge leads to difficulties in interpretation of the results of IBS treatments, particularly those involving probiotics. The research proposed in this application will profile microflora composition in healthy children and in children with IBS undergoing probiotic treatment. The comparisons of microflora composition between these children will i) provide information on microflora status during IBS in children and its changes as a result of probiotic treatment, ii) expedite the evaluation and development of new therapeutic options such as probiotic agents aimed to restore normal microflora composition; and iii) establish the base of knowledge on microflora composition necessary for further studies of probiotic effects on microflora.