溃疡性结肠炎患者粪便微生物群移植后肠道微生物群的动态变化:成功与否与控制前孢子菌有关

Susanne Pinto, Dominika Šajbenová, Elisa Benincà, Sam Nooij, Elisabeth M Terveer, Josbert J Keller, Andrea E van der Meulen-de Jong, Johannes A Bogaards, Ewout Steyerberg
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引用次数: 0

摘要

背景:粪便微生物群移植(FMT)是一种治疗溃疡性结肠炎(UC)的实验性疗法。我们旨在研究与 FMT 治疗成功相关的微生物家族:我们分析了 24 名接受每周四次 FMT 治疗的 UC 患者的粪便,这些患者随机接受了布地奈德(12 人)或安慰剂(12 人)的三周预处理。在 FMT 治疗前、治疗中和治疗后收集了九次粪便样本。研究开始 14 周后,采用梅奥评分法评估临床和内镜反应。因 UC 症状恶化而提前退出的患者被归类为无应答:9名患者(38%)在第14周达到缓解,15名患者在第14周或之前出现部分反应或无反应。根据纵向收集的 180 份患者样本和 27 份捐赠者样本的微生物群组成,我们利用 Dirichlet 多叉混合模型确定了五个不同的群组。前胡科为主的群组与对 FMT 治疗反应差有关。相反,反刍球菌科(Ruminococcaceae)和漆树科(Lachnospiraceae)则与成功的临床反应有关。这些关联在开始治疗时就已经在一部分患者中显现出来,并随着时间的推移在对特定科丰度的重复测量分析中得以保留。与非应答者相比,应答者的辛普森优势度也明显较低:结论:对 UC 患者进行 FMT 治疗的成功与否似乎与特定的肠道微生物群系有关,例如对前胡科微生物群系的控制。监测这些微生物群系的动态可能会在 FMT 治疗的早期为治疗的成功提供信息。
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Dynamics of Gut Microbiota after Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae.

Background: Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success.

Methods: We analyzed stools from 24 UC patients treated with four FMTs weekly after randomization for pretreatment during three weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected nine times pre-, during, and post FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response.

Results: Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet Multinomial Mixture model we identified five distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders.

Conclusions: The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.

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