Gut Microbial Species and Endotypes Associate with Remission in Ulcerative Colitis Patients Treated with Anti-TNF or Anti-integrin Therapy.

Fiona B Tamburini, Anupriya Tripathi, Maxwell P Gold, Julianne C Yang, Tommaso Biancalani, Jacqueline M McBride, Mary E Keir, Gardenia Study Group
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Abstract

Background and aims: The gut microbiota contributes to aberrant inflammation in inflammatory bowel disease, but the bacterial factors causing or exacerbating inflammation are not fully understood. Further, the predictive or prognostic value of gut microbial biomarkers for remission in response to biologic therapy is unclear.

Methods: We perform whole metagenomic sequencing of 550 stool samples from 287 ulcerative colitis patients from a large, phase 3, head-to-head study of infliximab and etrolizumab.

Results: We identify several bacterial species in baseline and/or post-treatment samples that associate with clinical remission. These include previously described associations [Faecalibacterium prausnitzii_F] as well as new associations with remission to biologic therapy [Flavonifractor plautii]. We build multivariate models and find that gut microbial species are better predictors for remission than clinical variables alone. Finally, we describe patient groups that differ in microbiome composition and remission rate after induction therapy, suggesting the potential utility of microbiome-based endotyping.

Conclusions: In this large study of ulcerative colitis patients, we show that few individual species associate strongly with clinical remission, but multivariate models including microbiome can predict clinical remission and have better predictive power compared with clinical data alone.

肠道微生物种类和内型与接受抗肿瘤坏死因子或抗整合素治疗的溃疡性结肠炎患者病情缓解有关。
背景和目的:肠道微生物群导致了炎症性肠病的异常炎症,但导致或加剧炎症的细菌因素尚未完全明了。此外,肠道微生物生物标志物对生物疗法缓解的预测或预后价值尚不明确:我们对英夫利昔单抗和依托利珠单抗 3 期头对头大型研究中 287 名溃疡性结肠炎患者的 550 份粪便样本进行了全元基因组测序:结果:我们在基线和/或治疗后样本中发现了与临床缓解相关的几种细菌物种。结果:我们在基线和/或治疗后样本中发现了与临床缓解相关的几种细菌,其中包括之前描述过的相关细菌(Faecalibacterium prausnitzii_F)以及与生物治疗缓解相关的新细菌(Flavonifractor plautii)。我们建立了多变量模型,发现肠道微生物种类比单独的临床变量更能预测病情缓解。最后,我们描述了在诱导治疗后微生物组组成和缓解率方面存在差异的患者群体,这表明基于微生物组的内分型具有潜在的实用性:结论:在这项针对溃疡性结肠炎患者的大型研究中,我们发现很少有单个物种与临床缓解密切相关,但是包括微生物组在内的多变量模型可以预测临床缓解,并且与单独的临床数据相比具有更好的预测能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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