Center for Gastrointestinal Biology and Disease, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Department of Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Nat Rev Gastroenterol Hepatol. 2019 May;16(5):296-311. doi: 10.1038/s41575-019-0118-x.
The IBDs, Crohn's disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract resulting from an aberrant immune response to enteric microbiota in genetically susceptible individuals. Disease presentation and progression within and across IBDs, especially Crohn's disease, are highly heterogeneous in location, severity of inflammation and other phenotypes. Current clinical classifications fail to accurately predict disease course and response to therapies. Genome-wide association studies have identified >240 loci that confer risk of IBD, but the clinical utility of these findings remains unclear, and mechanisms by which the genetic variants contribute to disease are largely unknown. In the past 5 years, the profiling of genome-wide gene expression, epigenomic features and gut microbiota composition in intestinal tissue and faecal samples has uncovered distinct molecular signatures that define IBD subtypes, including within Crohn's disease and ulcerative colitis. In this Review, we summarize studies in both adult and paediatric patients that have identified different IBD subtypes, which in some cases have been associated with distinct clinical phenotypes. We posit that genome-scale molecular phenotyping in large cohorts holds great promise not only to further our understanding of the diverse molecular causes of IBD but also for improving clinical trial design to develop more personalized disease management and treatment.
IBD 包括克罗恩病和溃疡性结肠炎，是一种胃肠道慢性炎症性疾病，由遗传易感个体对肠道微生物群的异常免疫反应引起。在 IBD 中，尤其是在克罗恩病中，疾病的表现和进展在部位、炎症严重程度和其他表型方面存在高度异质性。目前的临床分类方法无法准确预测疾病进程和对治疗的反应。全基因组关联研究已经确定了>240 个与 IBD 风险相关的位点，但这些发现的临床应用仍不清楚，遗传变异如何导致疾病的机制在很大程度上尚不清楚。在过去的 5 年中，对肠道组织和粪便样本中全基因组基因表达、表观基因组特征和肠道微生物组成的分析揭示了不同的分子特征，这些特征定义了 IBD 亚型，包括克罗恩病和溃疡性结肠炎中的亚型。在这篇综述中，我们总结了在成人和儿科患者中进行的研究，这些研究已经确定了不同的 IBD 亚型，在某些情况下，这些亚型与不同的临床表型相关。我们认为，在大型队列中进行全基因组分子表型分析不仅有望进一步了解 IBD 的多种分子病因，还有望改善临床试验设计，以制定更个性化的疾病管理和治疗方法。
