Translational Immunology Research Program, University of Helsinki, Helsinki, Finland.
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Sci Rep. 2022 Apr 22;12(1):6654. doi: 10.1038/s41598-022-10548-7.
Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.
儿科炎症性肠病(PIBD)是一种全球范围内不断增加的慢性炎症性疾病,与肠道微生物群落失衡有关,可采用多种治疗方法,包括抗肿瘤坏死因子-α(TNF-α),如英夫利昔单抗(IFX)。多达一半的患者对该药物没有反应,而且目前还没有预测反应的方法。我们的目的是从肠道微生物群落组成预测 IFX 反应,因为这在 PIBD 中很大程度上尚未得到探索。对 30 名接受 IFX 治疗的 PIBD 患者的肠道微生物群进行了研究,通过对粪便样本进行 MiSeq 测序,靶向 16S 和 ITS 区域,这些样本是在开始治疗前、治疗开始后 2 周和 6 周收集的。通过粪便钙卫蛋白值<100μg/g 在第 6 周来确定 IFX 诱导的反应。应答组和无应答组的细菌微生物群存在显著差异,与无应答组相比,应答组在基线时丁酸产生菌的相对丰度更高,这通过对基线鲁米诺克斯和钙卫蛋白的高预测能力(曲线下面积=0.892)得到了验证。此外,无应答组中念珠菌的丰度更高,而应答组在研究结束时酵母菌的丰度更高。PIBD 患者的肠道微生物群组成可以预测未来对 IFX 治疗的反应。