Human Pathobiology & OMNI Reverse Translation, Genentech, South San Francisco, CA, USA.
Prescient Design, Genentech, South San Francisco, CA, USA.
J Crohns Colitis. 2024 Nov 4;18(11):1819-1831. doi: 10.1093/ecco-jcc/jjae084.
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.
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.
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.
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.
肠道微生物群有助于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阐明。此外，肠道微生物生物标志物对生物治疗反应缓解的预测或预后价值尚不清楚。
我们对来自一项大型、3 期、英夫利昔单抗和埃特罗利珠单抗头对头研究的 287 例溃疡性结肠炎患者的 550 个粪便样本进行了全宏基因组测序。
我们在基线和/或治疗后样本中鉴定出几种与临床缓解相关的细菌物种。其中包括先前描述的关联[普氏粪杆菌_F]以及与生物治疗缓解的新关联[Flavonifractor plautii]。我们建立了多变量模型，发现肠道微生物物种是缓解的更好预测因子，优于单独的临床变量。最后，我们描述了诱导治疗后微生物组组成和缓解率不同的患者群体，这表明基于微生物组的终末分型具有潜在的应用价值。
在这项对溃疡性结肠炎患者的大型研究中，我们表明，少数个体物种与临床缓解密切相关，但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。
