Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
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DOI：
10.1038/s41586-019-1237-9
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发表时间：
2019-05-30
期刊：
影响因子：
64.8
通讯作者：
Yajnik, Vijay
中科院分区：
文献类型：
--
作者：
Lloyd-Price, Jason;Arze, Cesar;Yajnik, Vijay
炎症性肠病，包括克罗恩病和溃疡性结肠炎，影响全世界数百万人。克罗恩病和溃疡性结肠炎是复杂的疾病，在临床、免疫学、分子、遗传和微生物水平上具有异质性。个体因素一直是广泛研究的焦点。作为综合人类微生物组项目（HMP 2或iHMP）的一部分，我们对132名受试者进行了为期一年的随访，以生成疾病期间宿主和微生物活性的综合纵向分子谱（每个时间点最多24个;总共2，965份粪便，活检和血液标本）。在这里，我们提出了这些结果，这些结果提供了炎症性肠病活动期间肠道微生物组功能性生态失调的全面观点。我们证明了一个特征性的增加兼性厌氧菌的代价，专性厌氧菌，以及在微生物转录的分子中断（例如，梭菌），代谢物池（酰基肉毒碱，胆汁酸，短链脂肪酸），和宿主血清中的抗体水平。疾病活动期的时间变异性增加，特征分类，功能和生化变化。最后，综合分析确定了微生物，生化和宿主因素的核心，这种失调。该研究的基础设施资源、结果和数据可通过炎症性肠病多组学数据库（http：//www.example.com）获得，提供了迄今为止炎症性肠病中宿主和微生物活性的最全面描述。ibdmdb.org
Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.