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小儿炎症性肠病中的粪便微生物组改变。

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease.

机构信息

VTT Technical Research Centre of Finland, Espoo, Finland

Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.

出版信息

J Crohns Colitis. 2015 Dec;9(12):1088-95. doi: 10.1093/ecco-jcc/jjv147. Epub 2015 Sep 7.

Abstract

BACKGROUND AND AIMS

Several factors support the view of inflammatory bowel disease [IBD] origin in the host responsiveness to intestinal bacteria, although no single bacterial species has been shown as a causative agent in the pathogenesis. Our aim was to analyse the fecal microbiota of paediatric IBD patients at different stages of the disease. In addition, the characteristics of immune response to the bacterial isolates showing very low abundance in IBD were studied.

METHODS

Fecal samples [1-3 samples/child] were collected from 10 paediatric patients with crohn's disease [CD], and 12 with ulcerative colitis [UC] and from 8 healthy children, for polyphasic microbiological analysis (culture, real-time polymerase chain reaction [PCR], and denaturing gradient gel electrophoresis). In addition, in vitro cytokine responses of peripheral blood mononuclear cells to the bacterial isolates, which showed very low abundance in IBD, were studied.

RESULTS

Although predominant bacterial diversity was higher in IBD, the numbers of Lachnospiraceae and Coriobacteriaceae bacteria were lower in IBD patients as compared with control children [p < 0.05]. In addition, Ruminococcaceae population diversity was lower in IBD [p < 0.05] and correlated negatively with fecal calprotectin levels. Both abundance and diversity of bifidobacterial populations were lower in children with IBD [p < 0.05], and particularly low numbers of certain bifidobacterial isolates were detected. In CD, we found enhanced up-regulation of interleukin-6 transcripts and impaired RAR-related orphan receptor C response to bifidobacteria, whereas decreased interferon-gamma response was observed in both CD and UC.

CONCLUSION

We demonstrate altered fecal microbiota in paediatric IBD, particularly low numbers and diversity of bifidobacterial populations. Interestingly, immunological response to bifidobacteria differed between paediatric CD patients and control children.

摘要

背景与目的

尽管没有单一的细菌物种被证明是发病机制中的致病因子,但有几个因素支持炎症性肠病[IBD]起源于宿主对肠道细菌的反应。我们的目的是分析不同疾病阶段的小儿 IBD 患者的粪便微生物群。此外,还研究了对 IBD 中丰度非常低的细菌分离株的免疫反应特征。

方法

收集 10 名克罗恩病[CD]患儿、12 名溃疡性结肠炎[UC]患儿和 8 名健康儿童的粪便样本[每个儿童 1-3 个样本],进行多相微生物分析(培养、实时聚合酶链反应[PCR]和变性梯度凝胶电泳)。此外,研究了对 IBD 中丰度非常低的细菌分离株的体外外周血单核细胞细胞因子反应。

结果

尽管 IBD 中优势细菌多样性较高,但与对照组儿童相比,IBD 患者的lachnospiraceae 和 coriobacteriaceae 细菌数量较低[P<0.05]。此外,IBD 患者的 ruminococcaceae 种群多样性较低[P<0.05],与粪便钙卫蛋白水平呈负相关。IBD 患儿双歧杆菌种群的丰度和多样性均较低[P<0.05],特别是某些双歧杆菌分离株的数量较低。在 CD 中,我们发现白细胞介素-6 转录物的上调增强,双歧杆菌对 RAR 相关孤儿受体 C 的反应受损,而在 CD 和 UC 中均观察到干扰素-γ反应下降。

结论

我们证明了小儿 IBD 粪便微生物群发生改变,特别是双歧杆菌种群数量和多样性降低。有趣的是,双歧杆菌的免疫反应在小儿 CD 患者和对照组儿童之间存在差异。

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