Characterizing the gut microbial ecosystem for diagnosis and therapy in IBD

描述(申请人提供)：炎症性肠弓/肠炎(IBD)包括克罗恩病(CD)和溃疡性结肠炎(UC)，影响约150万美国人。-25%的病例发生在儿童中，总发病率在过去50年中增加了400%。CD和UC都是复杂的疾病，在不同的患者中表现和进展不同，最近的研究发现，它们的遗传风险同样复杂。对环境与IBD相关性的研究尚未产生简单的诊断标志物或可治疗的干预点。相反，IBD已经成为与肠道微生物区系有关的最重要的人类疾病之一，肠道微生物区系是通常驻留在肠道中的细菌、病毒、古生物和真菌的复杂混合物。IBD与肠道微生物的关联又是复杂的，似乎没有单一的微生物或病原体是致病原因。相反，IBD被反复地与整个肠道微生物生态系统的整体生态联系在一起。这表明，通过整合多种不同类型的肠道微生物测量来研究这种疾病可能是最好的，因为它们在IBD患者和非IBD对照组中随着时间的推移而发生变化。因此，该项目将在IBD多组数据库IBDMDB中提供这些数据，IBDMDB是一个综合资源，使肠道微生物生态系统成为诊断、治疗和了解IBD机制的目标。它将利用现有的表型良好的队列来提供肠道微生物组的纵向分类、元基因组、元翻译组、元蛋白质组和代谢组谱。为了进一步提供关于宿主相互作用机制的数据，我们将介绍宿主遗传学、表观遗传学和转录活性。这些数据将在一年内从90个受试者中产生，并将通过建立在我们现有的综合计算基础设施上，迅速和可访问地提供给社区。样本收集和生物信息学方案都将得到验证和分发，这项研究将产生面向单细胞和以宿主为重点的代谢组学分析的平台。我们的团队包括研究人类微生物群、IBD、微生物群落生态和功能以及代谢数据整合的领导者。我们组织了一个不同的合作者小组，包括人类微生物组项目的主要参与者。我们的组织包括项目管理、样本生成和数据生成、包括五个不同的多组学平台和技术开发的分析以及计算基础设施的组件。我们致力于及时向公众发布所有生成的数据，同时在必要时使用受控访问数据库维护主体隐私。我们已经收集了必要的专业知识和资源，以构建一个明确的多组数据资源，以了解肠道微生物组在IBD中的作用。

DESCRIPTION (provided by applicant): Inflammatory bow/el diseases (IBD) comprise both Crohn's disease (CD) and-ulcerative colitis (UC) and affect some 1.5 million Americans. -25% of cases occur in children, and overall incidence has increased >400% in the past 50 years. CD and UC are both complex diseases that can manifest and proceed differently among patients, and recent studies have found that their genetic risk is likewise complex. Studies of environmental associations with IBD have not yet resulted in simple diagnostic markers or treatable points of intervention. Instead, IBD has emerged in as one of the most important human conditions linked to the gut microbiota, the complex mixture of bacterial, viral, archaeal, and fungal organisms normally resident in the gut. The association of IBD with gut microbes is again complex, with no single microbe or pathogen appearing to be causal. Instead, IBD has been repeatedly linked to the overall ecology of entire gut microbial ecosystem. This suggests that the disease may be best studied by integrating many different types of measurements of gut microbes as they change within IBD patients and non-IBD controls over time. This project will thus provide such data in an IBD multi'omic database, the IBDMDB, an integrated resource enabling the gut microbial ecosystem as a target for diagnosis, therapy, and mechanistic understanding of IBD. It will leverage existing, well-phenotyped cohorts to provide longitudinal taxonomic, metagenomic, metatranscriptomic, metaproteomic, and metabolomic profiling of the gut microbiome. To further provide data on host interaction mechanisms, we will profile host genetics, epigenetics, and transcriptional activity. These data will be generated from 90 subjects over one year, and they will be made rapidly and accessibly available to the community by building on our current meta'omic computational infrastructure. Both sample collection and bioinformatic protocols will be validated and distributed, and the study will result in fonward-looking platforms for single-cell and host-focused meta'omic assays. Our team includes leaders in the study of the human microbiome, IBD, microbial community ecology and function, and meta'omic data integration. We have organized a diverse group of collaborators, including key players in the Human Microbiome Project. Our organization includes Components for Project Management; Sample Generation and Data Generation; assays including five different multi'omics platforms and Technology Development; and Computational Infrastructure. We are committed to releasing all generated data to the public in a timely manner while maintaining subject privacy using controlled access databases whenever necessary. We have assembled the expertise and resources necessary to construct a definitive multi'omic data resource to understand the gut microbiome's role in IBD.