Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore University Medical Center, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), 14 Medical Drive, MD6-Centre for Translational Medicine, Singapore 117599, Singapore.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Host Microbe. 2021 Aug 11;29(8):1294-1304.e4. doi: 10.1016/j.chom.2021.06.019. Epub 2021 Jul 22.
The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success. In this prospective study, we profiled baseline stool and blood in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-cytokine therapy (anti-TNF or -IL12/23) or anti-integrin therapy. Patients were assessed at 14 weeks for clinical remission and 52 weeks for clinical and endoscopic remission. Baseline microbial richness indicated preferential responses to anti-cytokine therapy and correlated with the abundance of microbial species capable of 7α/β-dehydroxylation of primary to secondary bile acids. Serum signatures of immune proteins reflecting microbial diversity identified patients more likely to achieve remission with anti-cytokine therapy. Remission-associated multi-omic profiles were unique to each therapeutic class. These profiles may facilitate a priori determination of optimal therapeutics for patients and serve as targets for newer therapies.
肠道微生物组是决定炎症性肠病（IBD）对生物治疗反应的关键因素。然而，IBD 患者的治疗方法多种多样，反应也各不相同，这给预测临床治疗效果带来了挑战。在这项前瞻性研究中，我们对接受抗细胞因子治疗（抗 TNF 或抗 IL12/23）或抗整合素治疗的中重度克罗恩病或溃疡性结肠炎患者进行了基线粪便和血液分析。患者在第 14 周时评估临床缓解情况，在第 52 周时评估临床和内镜缓解情况。基线微生物丰富度表明对抗细胞因子治疗有优先反应，并与能够进行初级胆汁酸 7α/β-去羟化的微生物物种丰度相关。反映微生物多样性的免疫蛋白的血清特征可识别出更有可能通过抗细胞因子治疗缓解的患者。与缓解相关的多组学特征在每种治疗类别中都是独特的。这些特征可能有助于事先为患者确定最佳治疗方法，并为新的治疗方法提供目标。
