Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts; Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Gastroenterology. 2014 May;146(6):1489-99. doi: 10.1053/j.gastro.2014.02.009. Epub 2014 Feb 19.
Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general.
对微生物群落在炎症性肠病(IBD)发展中所起作用的研究已达到一个重要的里程碑。十年来,全基因组关联研究和其他遗传分析将 IBD 与涉及对肠道微生物群异常免疫反应的基因座联系起来。最近,对肠道微生物组的分析研究将 IBD 的发病机制与肠道微生物群组成的特征性变化联系起来,进一步证实了 IBD 是由于肠道微生物和黏膜免疫系统之间的相互作用改变所致。增强型技术可以提高我们对宿主与其常驻微生物群之间相互作用的理解,并从大规模途径和代谢水平上了解它们各自在 IBD 中的作用。我们回顾了 IBD 患者的重要微生物组研究,并描述了我们在了解肠道微生物群功能障碍的机制方面所学到的知识。我们描述了最近在微生物组研究方面的进展,从基于 16S 的探索性研究,报告特定生物体与疾病的关联,到最近的更细致的研究,这些研究通过宏基因组学和代谢组学方法解决了微生物群的功能问题。最后,我们提出了用于研究炎症性肠道和一般自身免疫性疾病患者微生物组的研究设计和方法学。