The Interplay between Mucosal Microbiota Composition and Host Gene-Expression is Linked with Infliximab Response in Inflammatory Bowel Diseases
The Interplay between Mucosal Microbiota Composition and Host Gene-Expression is Linked with Infliximab Response in Inflammatory Bowel Diseases
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DOI：
10.3390/microorganisms8030438
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发表时间：
2020-03-01
期刊：
影响因子：
4.5
通讯作者：
Gazouli, Maria
中科院分区：
文献类型：
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作者：
Dovrolis, Nikolas;Michalopoulos, George;Gazouli, Maria
尽管抗肿瘤坏死因子治疗可显著提高炎症性肠病（IBD）患者的缓解率，但仍有一部分患者对治疗无反应。生态失调是IBD发病的一个关键因素。本研究的目的是分析抗肿瘤坏死因子药物英夫利昔单抗（IFX）给药前后肠道微生物组和转录组的变化，并研究它们在基线时预测患者对IFX反应的潜力。20名IBD患者和9名健康对照（HC）的粘膜活检样本在基线和IFX治疗完成后，通过硅管道检测微生物群组成（16S rRNA基因测序）和粘膜基因表达（RT-qPCR）的差异。IBD组和HC组之间的微生物群组成存在显著差异。几种仅在IBD患者而非HC患者中发现的细菌属，在抗tnf治疗后无论疗效如何，其种群数量都显着减少。α和β多样性指标显示我们的研究组之间存在显著差异。相关分析显示，在基线时IFX治疗应答者中，有6种微生物属与炎症相关基因的差异表达相关。本研究表明，IFX治疗对IBD患者肠道微生物组成和炎症组织转录组均有显著影响。重要的是，我们的研究结果确定了与转录组变化相关的肠型，并有助于区分IFX应答者和无应答者，这表明，结合起来，这些特征可以成为预测抗tnf应答的有效工具。
Even though anti-TNF therapy significantly improves the rates of remission in inflammatory bowel disease (IBD) patients, there is a noticeable subgroup of patients who do not respond to treatment. Dysbiosis emerges as a key factor in IBD pathogenesis. The aim of the present study is to profile changes in the gut microbiome and transcriptome before and after administration of the anti-TNF agent Infliximab (IFX) and investigate their potential to predict patient response to IFX at baseline. Mucosal biopsy samples from 20 IBD patients and nine healthy controls (HC) were examined for differences in microbiota composition (16S rRNA gene sequencing) and mucosal gene expression (RT-qPCR) at baseline and upon completion of IFX treatment, accordingly, via an in silico pipeline. Significant differences in microbiota composition were found between the IBD and HC groups. Several bacterial genera, which were found only in IBD patients and not HC, had their populations dramatically reduced after anti-TNF treatment regardless of response. Alpha and beta diversity metrics showed significant differences between our study groups. Correlation analysis revealed six microbial genera associated with differential expression of inflammation-associated genes in IFX treatment responders at baseline. This study shows that IFX treatment has a notable impact on both the gut microbial composition and the inflamed tissue transcriptome in IBD patients. Importantly, our results identify enterotypes that correlate with transcriptome changes and help differentiate IFX responders versus non-responders at baseline, suggesting that, in combination, these signatures can be an effective tool to predict anti-TNF response.