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.

肠道微生物组是炎症性肠病 (IBD) 生物治疗反应的关键决定因素。然而，IBD 患者的多种治疗方法和不同的反应对预测临床治疗成功提出了挑战。在这项前瞻性研究中，我们对中度至重度克罗恩病或溃疡性结肠炎患者开始抗细胞因子治疗（抗 TNF 或 -IL12/23）或抗整合素治疗的基线粪便和血液进行了分析。在 14 周评估患者的临床缓解情况，并在 52 周评估患者的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的优先反应，并与能够对初级至次级胆汁酸进行 7α/β-脱羟基的微生物种类的丰度相关。反映微生物多样性的免疫蛋白的血清特征确定了患者更有可能通过抗细胞因子治疗获得缓解。缓解相关的多组学特征对于每个治疗类别都是独一无二的。这些配置文件可能有助于先验确定患者的最佳治疗方法，并作为新疗法的目标。