Characterizing the gut microbial ecosystem for diagnosis and therapy in IBD

表征肠道微生物生态系统以用于 IBD 的诊断和治疗

• 批准号: 8731194
• 负责人: Curtis Huttenhower
• 金额: $ 250万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-06 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731194
• 关键词: Adult; Affect; Algorithms; American; Bioinformatics; Biological; Biological Assay; Biopsy; Biopsy Specimen; Cells; Child; Childhood; Clinical; Collaborations; Collection; Colon; Commit; Communities; Complex; Complex Mixtures; Crohn' s disease; DNA Methylation; Data; Data Set; Databases; Development; Diagnosis; Diagnostic; Disease; Ecology; Ecosystem; Epigenetic Process; Epithelial Cells; Feces; Future; Gene Expression; Generations; Genetic; Genetic Risk; Health; Human; Human Genetics; Human Microbiome; Human body; Incidence; Individual; Inflammatory; Inflammatory Bowel Diseases; Institution; Intervention; Intestines; Link; Measurement; Metabolic; Metadata; Metagenomics; Methods; Microbe; Organism; Patients; Phenotype; Population; Privacy; Proteomics; Protocols documentation; Publications; Recruitment Activity; Resources; Role; Sampling; Serologic tests; Surveys; Techniques; Time; Ulcerative Colitis; Viral; cohort; computer infrastructure; computerized data processing; data integration; disorder control; gut microbiota; human ecology; metabolomics; microbial; microbial community; microbial host; microbiome; pathogen; protein metabolite; rectal; response; sample collection; technology development; time use; virome

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 forward-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.

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 这可能会在患者中表现出不同的表现和进展，最近的研究发现，他们的遗传风险也同样复杂。研究 环境因素与IBD的相关性尚未形成简单的诊断标记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，肠道微生物区系是细菌、病毒、古生菌、 和真菌生物通常驻留在肠道中。IBD与肠道微生物的关联又是复杂的，没有单一的微生物或 病原体似乎是有原因的。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 这表明，研究这种疾病的最佳方法可能是整合多种不同类型的肠道微生物测量数据，因为它们在肠道内发生变化。 随着时间的推移，IBD患者和非IBD对照组。因此，该项目将在IBD多组学数据库、IBDMDB和 整合的资源使肠道微生物生态系统成为IBD诊断、治疗和机制理解的目标。会的 利用现有的表型良好的队列来提供纵向分类、元基因组、元翻译、元蛋白质组和 肠道微生物组的代谢组谱。为了进一步提供关于寄主相互作用机制的数据，我们将介绍寄主遗传学， 表观遗传学和转录活性。这些数据将在一年内从90名受试者中产生，并将迅速和 通过构建我们当前的元计算基础设施，可供社区访问。样本收集和 生物信息学协议将得到验证和分发，这项研究将产生面向单细胞和以宿主为中心的前瞻性平台 代谢组学分析。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的领导者，以及 元数据集成。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 组织包括用于项目管理的组件；样本生成和数据生成；分析包括五个不同的 多组学平台和技术开发；以及计算基础设施。我们致力于将所有生成的数据发布到 在必要时使用受控访问数据库维护主体隐私的同时，及时向公众开放。我们已经集合好了 所需的专业知识和资源，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。