ABSTRACT

Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn’s disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6–10.3, P < .01) and 3.56 (95% CI 1.4–9.2, P < .01)). In this multicentre observational study, a limited number of taxa were associated with neoplasia and exploratory microbiota clusters co-associated with clinical features, including neoplasia risk in UC. Given the very small number of cancers, the robustness of these findings will require assessment and validation in future studies.

摘要

由于肠道微生物群和胆汁酸在炎症性肠病 (IBD) 和散发性结直肠癌发病机制中的潜在作用，我们旨在确定这些因素是否与 IBD 患者的结直肠癌相关。2011 年 9 月至 2018 年 7 月期间，从 10 个法国 IBD 中心招募了 215 名 IBD 患者和 51 名非 IBD 对照受试者。对粪便样本进行了细菌 16S rRNA 基因测序和胆汁酸分析。记录人口统计学、临床、内窥镜和组织学结果。IBD 患者的特征包括：中位年龄：41.6（IQR 22）；病程13.2（13.1）；47% 女性；21.9% 原发性硬化性胆管炎；109 名克罗恩病 (CD) 患者；106 名溃疡性结肠炎 (UC) 患者。癌症患病率为 2.8%（6/215：1 CD；5 UC），患有癌症的 IBD 患者中毛螺菌属减少，而Agathobacter减少，大肠杆菌-志贺氏菌减少在患有任何肿瘤的 UC 患者中增加。胆汁酸与癌症或瘤形成无关。无监督聚类在 IBD 患者中确定了与胆汁酸成分和临床特征相关的三个肠道微生物群簇，包括与第三个簇相比，两个簇中的 UC 肿瘤形成风险更高（相对风险 (RR) 4.07 (95% CI 1.6–10.3, P < .01) 和 3.56 (95% CI 1.4–9.2, P < .01))。在这项多中心观察性研究中，有限数量的分类群与肿瘤形成相关，而探索性微生物群簇与临床特征（包括 UC 中的肿瘤形成风险）共同相关。鉴于癌症的数量非常少，这些发现的稳健性将需要在未来的研究中进行评估和验证。