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.

炎症性弓/EL疾病（IBD）既包括克罗恩病（CD）和剥离结肠炎（UC），并影响约150万美国人。 - 25％的病例发生在儿童中，在过去的50年中，总体发病率> 400％。 CD和UC都是复杂的疾病 这可以在患者中表现出来，并且最近的研究发现它们的遗传风险同样是复杂的。研究 与IBD的环境关联尚未导致简单的诊断标记或可治疗的干预点。相反，IBD 已成为与肠道菌群相关的最重要的人类条件之一，这是细菌，病毒，古细菌的复杂混合物， 和真菌生物通常居住在肠道中。 IBD与肠道微生物的关联再次复杂，没有单一微生物或 病原体似乎是因果关系。取而代之的是，IBD与整个肠道微生物生态系统的整体生态学反复联系在一起。这 表明，可以通过整合肠道微生物的许多不同类型的测量方法来最好地研究这种疾病 随着时间的流逝，IBD患者和非IBD对照。因此，该项目将在IBD多'omic数据库IBDMDB中提供此类数据 综合资源使肠道微生物生态系统成为IBD诊断，治疗和机械理解的目标。会 利用现有的，良好的类型队列来提供纵向分类学，宏基因组，元文字，元蛋白质组学和 肠道微生物组的代谢组分析。为了进一步提供有关宿主交互机制的数据，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名受试者中产生，它们将迅速制作，并且 通过在我们当前的元元计算基础架构上构建，可以访问社区。样本收集和 生物信息学协议将得到验证和分发，该研究将为单细胞和以主机为中心的前瞻性平台提供前瞻性平台 meta'omic测定法。我们的团队包括研究人类微生物组，IBD，微生物社区生态和功能的领导者，以及 元数据集成。我们已经组织了一组多样化的合作者，其中包括人类微生物项目的关键参与者。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；包括五个不同的测定 多'词平台和技术开发；和计算基础架构。我们致力于将所有生成的数据释放到 及时使用受控访问数据库维护主题隐私的方式及时及时。我们已经组装了 构建确定的多'元数据资源所需的专业知识和资源，以了解肠道微生物组在IBD中的作用。