Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
Gastroenterology. 2023 Sep;165(3):670-681. doi: 10.1053/j.gastro.2023.05.032. Epub 2023 May 30.
BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment.
In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort.
In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia.
This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.
克罗恩病（CD）的病因尚不清楚，但目前的假说认为，微生物或环境因素在遗传易感个体中诱导肠道炎症，导致慢性肠道炎症。对 CD 患者的病例对照研究已经对肠道微生物组组成的改变进行了编目；然而，这些研究未能区分肠道微生物组组成的改变是与 CD 的发生有关，还是炎症或药物治疗的结果。
在这项前瞻性队列研究中，招募了 3483 名 CD 患者的一级亲属（FDR），以确定先于 CD 发病的肠道微生物组组成，以及这种组成在多大程度上预测 CD 的发病风险。我们应用机器学习方法分析肠道微生物组组成（基于 16S 核糖体 RNA 测序），以定义与未来 CD 发展相关的微生物特征。该模型的性能在独立验证队列中进行了评估。
在验证队列中，使用发现队列中 MRS 的中位数作为阈值，微生物风险评分（MRS）模型的危险比为 2.24（95%置信区间，1.03-4.84；P=0.04）。MRS 通过捕获在疾病发病前长达 5 年发病的个体，表现出时间有效性（曲线下面积>0.65）。对 MRS 贡献最大的 5 个分类群包括 Ruminococcus torques、Blautia、Colidextribacter、Oscillospiraceae 未培养属级群和 Roseburia。
这项研究首次证明肠道微生物组组成与 CD 的未来发病有关，并表明肠道微生物组是 CD 发病机制的一个贡献者。
