Ananthakrishnan Ashwin N, Luo Chengwei, Yajnik Vijay, Khalili Hamed, Garber John J, Stevens Betsy W, Cleland Thomas, Xavier Ramnik J
Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Host Microbe. 2017 May 10;21(5):603-610.e3. doi: 10.1016/j.chom.2017.04.010.
The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment.
肠道微生物群在炎症性肠病（IBD）的发病机制和病情进展中起核心作用。为了确定肠道微生物群是否可以预测IBD治疗的反应，我们对开始抗整合素治疗（维多珠单抗）的克罗恩病（CD）或溃疡性结肠炎（UC）患者进行了一项前瞻性研究。评估了基线时以及治疗开始后第14、30和54周的疾病活动度和粪便宏基因组。在第14周达到缓解的CD患者中，群落α多样性在基线时显著更高，而食菊罗斯拜瑞氏菌和一种伯克霍尔德氏菌属物种更为丰富。确定了与微生物功能的几个显著关联；包括支链氨基酸合成在内的13条途径在达到缓解的CD患者的基线样本中显著富集。一种结合了微生物组和临床数据的神经网络算法vedoNet对临床缓解具有最高的分类能力。我们假设早期微生物组变化的轨迹可能是IBD治疗反应的一个标志。
