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使用英夫利昔单抗成功治疗炎症性肠病时,肠道黏膜和粪便中的细菌总量会增加。

The total gut mucosal and fecal bacterial load increases in successful treatment of inflammatory bowel disease with infliximab.

作者信息

Ventin-Holmberg Rebecka, Eriksson Julia, Eberl Anja, Sipponen Taina, Nissilä Eija, Saavalainen Päivi

机构信息

Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Folkhälsan Research Center, Helsinki, Finland.

出版信息

Microbiol Spectr. 2025 Aug 5;13(8):e0189424. doi: 10.1128/spectrum.01894-24. Epub 2025 Jul 7.

Abstract

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory gastrointestinal disorders linked to genetic predisposition and environmental factors. The gut microbiota, composed of various microorganisms, plays a crucial role in IBD, as reduced anaerobic bacteria and short-chain fatty acid (SCFA) producers are associated with predisposition to IBD. There is no cure for IBD, but the treatment aims for mucosal healing including conventional treatment and biological therapies such as infliximab (IFX). IFX, a tumor necrosis factor alpha (TNF-α) blocker, effectively reduces inflammation, but around 50% of patients do not achieve long-term remission. Fecal samples were collected from 70 patients with IBD (24 CD, 44 UC, and 2 IBDU), and mucosal samples were collected from both ileum and colon from 63 patients before, during, and after IFX treatment. The bacterial microbiota composition was investigated by targeting the conserved 16S region in MiSeq sequencing. Additionally, the relative sequencing data were quantified by qPCR. Responders to IFX had an increase in the total bacterial load in ileum and fecal samples during treatment, primarily driven by butyrate-producing bacteria in the Firmicutes phylum. Interestingly, this was only observed in the fecal samples in responders, but not non-responders to IFX. These results indicate that the gut bacterial microbiota of responders to IFX is changing toward a more favorable composition during successful IFX treatment.IMPORTANCEThe research described in this paper enhances our understanding of how infliximab (IFX) treatment affects the gut mucosal and fecal microbiota in patients with inflammatory bowel disease (IBD). Using 16S sequencing technique and quantification by qPCR, the study revealed that successful treatment with IFX led to an increase in the total bacterial load in both ileal and fecal samples, as well as a shift in bacterial composition toward a more favorable profile with an increase in butyrate-producing bacteria in the fecal samples in responders but not in non-responders to infliximab. This study emphasizes that the gut microbiota plays an important role in the healing process during infliximab treatment in IBD.

摘要

炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),是与遗传易感性和环境因素相关的慢性炎症性胃肠道疾病。由各种微生物组成的肠道微生物群在IBD中起着关键作用,因为厌氧细菌和短链脂肪酸(SCFA)产生菌数量减少与IBD易感性相关。IBD无法治愈,但治疗目标是实现黏膜愈合,包括传统治疗和生物疗法,如英夫利昔单抗(IFX)。IFX是一种肿瘤坏死因子α(TNF-α)阻滞剂,可有效减轻炎症,但约50%的患者无法实现长期缓解。从70例IBD患者(24例CD、44例UC和2例未定型IBD)中采集粪便样本,并在IFX治疗前、治疗期间和治疗后从63例患者的回肠和结肠采集黏膜样本。通过靶向MiSeq测序中保守的16S区域来研究细菌微生物群组成。此外,通过qPCR对相对测序数据进行定量分析。IFX治疗的反应者在治疗期间回肠和粪便样本中的总细菌载量增加,主要由厚壁菌门中产生丁酸盐的细菌驱动。有趣的是,这仅在IFX反应者的粪便样本中观察到,而在无反应者中未观察到。这些结果表明,在IFX成功治疗期间,IFX反应者的肠道细菌微生物群正朝着更有利的组成变化。

重要性

本文所述研究增进了我们对英夫利昔单抗(IFX)治疗如何影响炎症性肠病(IBD)患者肠道黏膜和粪便微生物群的理解。该研究使用16S测序技术并通过qPCR进行定量分析,结果显示IFX成功治疗导致回肠和粪便样本中的总细菌载量增加,以及细菌组成向更有利的特征转变,反应者粪便样本中产生丁酸盐的细菌增加,而英夫利昔单抗无反应者则未出现这种情况。这项研究强调肠道微生物群在IBD英夫利昔单抗治疗的愈合过程中起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ff4/12323318/ddbcdb1d6eca/spectrum.01894-24.f001.jpg

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