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糖皮质激素治疗与中重度溃疡性结肠炎患者肠道菌群的相关性:单中心回顾性研究

李映荷 孟祥辰 阎鹏光 杨红 李骥 钱家鸣 李景南

李映荷, 孟祥辰, 阎鹏光, 杨红, 李骥, 钱家鸣, 李景南. 糖皮质激素治疗与中重度溃疡性结肠炎患者肠道菌群的相关性:单中心回顾性研究[J]. 协和医学杂志, 2019, 10(3): 216-222. doi: 10.3969/j.issn.1674-9081.2019.03.006
引用本文: 李映荷, 孟祥辰, 阎鹏光, 杨红, 李骥, 钱家鸣, 李景南. 糖皮质激素治疗与中重度溃疡性结肠炎患者肠道菌群的相关性:单中心回顾性研究[J]. 协和医学杂志, 2019, 10(3): 216-222. doi: 10.3969/j.issn.1674-9081.2019.03.006
Ying-he LI, Xiang-chen MENG, Peng-guang YAN, Hong YANG, Ji LI, Jia-ming QIAN, Jing-nan LI. Relevance between Glucocorticoid Treatment and the Intestinal Microbiota of Patients with Moderately Severe Ulcerative Colitis: A Single-center Retrospective Study[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(3): 216-222. doi: 10.3969/j.issn.1674-9081.2019.03.006
Citation: Ying-he LI, Xiang-chen MENG, Peng-guang YAN, Hong YANG, Ji LI, Jia-ming QIAN, Jing-nan LI. Relevance between Glucocorticoid Treatment and the Intestinal Microbiota of Patients with Moderately Severe Ulcerative Colitis: A Single-center Retrospective Study[J]. Medical Journal of Peking Union Medical College Hospital, 2019, 10(3): 216-222. doi: 10.3969/j.issn.1674-9081.2019.03.006

糖皮质激素治疗与中重度溃疡性结肠炎患者肠道菌群的相关性:单中心回顾性研究

doi: 10.3969/j.issn.1674-9081.2019.03.006
基金项目: 

国家自然科学基金 81770559

中国医学科学院医学与健康科技创新工程 2016-12M-3-001

详细信息
    通讯作者:

    李景南 电话:010-69155017, E-mail:lijn2008@126.com

  • 中图分类号: R574.1;R574.62

Relevance between Glucocorticoid Treatment and the Intestinal Microbiota of Patients with Moderately Severe Ulcerative Colitis: A Single-center Retrospective Study

More Information
    Corresponding author: LI Jing-nan Tel: 86-10-69155017, E-mail: lijn2008@126.com
  • 摘要:   目的  分析接受及不接受糖皮质激素治疗的中重度溃疡性结肠炎(ulcerative colitis, UC)患者肠道菌群的差异, 并探讨肠道菌群对静脉糖皮质激素疗效的预测价值。  方法  回顾性分析2016年11月1日至2018年6月30日期间, 在北京协和医院消化内科门诊就诊或住院治疗的中重度UC患者临床资料。根据采集粪便样本时患者是否正在使用糖皮质激素, 将患者分为激素组和无激素组。无激素组患者入院后接受静脉激素、口服激素或免疫抑制剂治疗, 根据3 d后的疗效, 将入院后接受足量静脉激素治疗的患者分为治疗有效组和无效组。采用16S rRNA扩增子测序方法对粪便菌群测序分析, 采用香农指数评估肠道菌群α多样性, 采用Metastats分析比较不同组患者肠道菌群的物种构成差异。  结果  共35例符合入选和排除标准的中重度UC患者入选本研究, 无激素组20例, 激素组15例。无激素组中13例患者在采集粪便样本后接受静脉足量糖皮质激素治疗, 其中有效组8例, 无效组5例。激素组和无激素组患者的肠道菌群α多样性(香农指数:无激素组3.57±0.73, 激素组3.03±1.15, P=0.123)及物种组成无统计学差异。激素治疗有效组和无效组患者的肠道菌群α多样性亦无统计学差异(香农指数:有效组3.69±0.61, 无效组3.15±1.01, P=0.248), 但无效组的乳杆菌属(无效组0.0015±0.0000, 有效组0.0141±0.0002, P=0.010)和双歧杆菌属(无效组0.0178±0.0005, 有效组0.1716±0.0382, P=0.011)相对丰度显著低于有效组, 而志贺菌属(无效组0.4161±0.0750, 有效组0.1093±0.0173, P=0.008)和普雷沃氏菌属类群9(无效组0.0176±0.0004, 有效组0.0018±0.0000, P=0.044)的相对丰度则显著高于有效组。  结论  中重度UC患者肠道菌群的α多样性及物种组成可能与是否激素暴露无关, 但治疗前肠道菌群的物种组成可能是静脉激素疗效的潜在预测指标。
    利益冲突  无
  • 图  1  35例中重度溃疡性结肠炎患者门水平(A)和属水平(B)的菌群组成

    图  2  中重度溃疡性结肠炎无激素组和激素组患者肠道菌群差异分析

    A.菌群α多样性比较;B.菌群主成分分析;C.菌群相似性分析;D.菌群在门水平的构成;E.菌群在属水平的构成

    图  3  中重度溃疡性结肠炎患者激素治疗有效组和无效组间肠道菌群的差异

    A.菌群α多样性比较;B.菌群主成分分析;C.菌群相似性分析;D.菌群在门水平的构成; E.菌群在属水平的构成

    表  1  35例中重度溃疡性结肠炎患者一般临床资料及激素疗效比较

    指标 所有患者(n=35) 无激素组接受足量静脉激素治疗者(n=13)
    激素组 无激素组 t值或χ2 P 有效 无效 t值或χ2 P
    病例数(n) 15 20 - - 8 5 - -
    年龄(x±s,岁) 38.3±13.4 45.9±16.1 1.479 0.149 41.4±17.7 52.4±10.9 1.243 0.240
    性别(男/女,n) 9/6 11/9 0.088 0.767 4/4 4/1 1.229 0.268
    病变范围(E2/E3,n) 1/14 4/16 1.344 0.246 2/6 0/5 2.165 0.141
    疾病活动度(中度/重度,n) 9/6 12/8 0.000 1.000 5/3 2/3 0.630 0.427
    下载: 导出CSV

    表  2  中重度溃疡性结肠炎患者激素治疗有效组和无效组间细菌相对丰度比较

    菌门/属 有效组 无效组 P
    门水平
     变形菌门 0.1599±0.0279 0.4982±0.0794 0.017
     放线菌门 0.1971±0.0327 0.0236±0.0005 0.009
    属水平
     乳杆菌属 0.0141±0.0002 0.0015±0.0000 0.010
     双歧杆菌属 0.1716±0.0382 0.0178±0.0005 0.011
     Peptoclostridium 0.0167±0.0004 0.0013±0.0000 0.015
     志贺菌属 0.1093±0.0173 0.4161±0.0750 0.008
     普雷沃氏菌属类群9 0.0018±0.0000 0.0176±0.0004 0.044
    下载: 导出CSV
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  • 收稿日期:  2019-03-04
  • 刊出日期:  2020-09-18

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