Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Inflamm Bowel Dis. 2020 Sep 18;26(10):1524-1532. doi: 10.1093/ibd/izaa183.
Inflammatory bowel diseases (IBD) are characterized by intermittent relapses, and their course is heterogeneous and unpredictable. Our aim was to determine the ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease.
This prospective study enrolled patients with quiescent Crohn disease and ulcerative colitis, defined as the absence of clinical symptoms (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) and endoscopic remission within the prior year. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy or IBD-related hospitalization or surgery. Biomarkers were tested in a derivation cohort, and their performance was examined in an independent validation cohort.
Our prospective cohort study included 164 patients with IBD (108 with Crohn disease, 56 with ulcerative colitis). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (interleukin-10, glial cell line-derived neurotrophic factor, and T-cell surface glycoprotein CD8 alpha chain) and 4 metabolomic markers (propionyl-L-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models. Proteomic and metabolomic risk scores independently predicted relapse with a combined area under the curve of 0.83. A high proteomic risk score (odds ratio = 9.11; 95% confidence interval, 1.90-43.61) or metabolomic risk score (odds ratio = 5.79; 95% confidence interval, 1.24-27.11) independently predicted a higher risk of relapse over 2 years. Fecal metagenomics showed an increased abundance of Proteobacteria (P = 0.0019, q = 0.019) and Fusobacteria (P = 0.0040, q = 0.020) and at the species level Lachnospiraceae_bacterium_2_1_58FAA (P = 0.000008, q = 0.0009) among the relapses.
Proteomic, metabolomic, and microbial biomarkers identify a proinflammatory state in quiescent IBD that predisposes to clinical relapse.
炎症性肠病（IBD）的特点是间歇性复发，其病程具有异质性且不可预测。我们的目的是确定蛋白质、代谢物或微生物生物标志物是否能够预测处于缓解期的患者复发。
这项前瞻性研究纳入了处于缓解期的克罗恩病和溃疡性结肠炎患者，缓解期定义为过去 1 年内无临床症状（Harvey-Bradshaw 指数≤4，简单临床结肠炎活动指数≤2）和内镜缓解。主要结局为 2 年内复发，定义为症状加重伴炎症标志物升高，导致治疗改变或因 IBD 相关住院或手术。在推导队列中测试了生物标志物，并在独立验证队列中检验了其性能。
我们的前瞻性队列研究纳入了 164 例 IBD 患者（108 例克罗恩病，56 例溃疡性结肠炎）。中位随访 1 年后，22 例（13.4%）患者复发。在多变量模型中，有 3 种蛋白质生物标志物（白细胞介素-10、胶质细胞源性神经营养因子和 T 细胞表面糖蛋白 CD8 链）和 4 种代谢组学标志物（丙酰肉碱、肉碱、肌氨酸和山梨醇）与复发相关。蛋白质组学和代谢组学风险评分独立预测复发，联合曲线下面积为 0.83。高蛋白质组学风险评分（比值比=9.11；95%置信区间，1.90-43.61）或代谢组学风险评分（比值比=5.79；95%置信区间，1.24-27.11）独立预测 2 年内复发的风险更高。粪便宏基因组学显示，在复发中变形菌门（P=0.0019，q=0.019）和梭杆菌门（P=0.0040，q=0.020）的丰度增加，以及lachnospiraceae_bacterium_2_1_58FAA 种（P=0.000008，q=0.0009）的丰度增加。
蛋白质组学、代谢组学和微生物生物标志物可识别处于缓解期的 IBD 中的促炎状态，从而导致临床复发。
