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婴儿胆汁淤积的肠道菌群组成及功能变化

周建利 王朝霞 周少明 张巧 亁霞

周建利, 王朝霞, 周少明, 等. 婴儿胆汁淤积的肠道菌群组成及功能变化[J]. 临床肝胆病杂志, 2021, 37(1): 126-130. DOI: 10.3969/j.issn.1001-5256.2021.01.025
引用本文: 周建利, 王朝霞, 周少明, 等. 婴儿胆汁淤积的肠道菌群组成及功能变化[J]. 临床肝胆病杂志, 2021, 37(1): 126-130. DOI: 10.3969/j.issn.1001-5256.2021.01.025
ZHOU JL, WANG ZX, ZHOU SM, et al. Composition and functional change of intestinal microbiota in infantile cholestasis [J]. J Clin Hepatol, 2021, 37(1): 126-130. DOI: 10.3969/j.issn.1001-5256.2021.01.025
Citation: ZHOU JL, WANG ZX, ZHOU SM, et al. Composition and functional change of intestinal microbiota in infantile cholestasis [J]. J Clin Hepatol, 2021, 37(1): 126-130. DOI: 10.3969/j.issn.1001-5256.2021.01.025

婴儿胆汁淤积的肠道菌群组成及功能变化

DOI: 10.3969/j.issn.1001-5256.2021.01.025
基金项目: 

深圳市科技计划项目 JCYJ20160429174706491

详细信息
    作者简介:

    周建利(1989—),男,主治医师,主要从事婴儿胆汁淤积、儿童脂肪肝等研究

    通讯作者:

    周少明,zhousm15d@aliyun.com

  • 利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突,特此声明。
  • 作者贡献声明:周建利、王朝霞、周少明等负责课题设计,资料分析,撰写论文; 张巧、亁霞等参与收集数据,修改论文; 王朝霞、周少明等负责拟定写作思路,指导撰写文章并最后定稿。
  • 中图分类号: R575.6

Composition and functional change of intestinal microbiota in infantile cholestasis

  • 摘要:   目的  研究胆汁淤积婴儿的肠道菌群组成及功能变化。  方法  纳入2014年9月—2016年2月深圳市儿童医院收治的42例胆汁淤积婴儿(胆汁淤积组)及同期32例正常对照婴儿(对照组),收集以上婴儿的大便标本,采用鸟枪法测序了解入选婴儿肠道菌群特征,应用京都基因与基因组百科全书、eggNOG数据库探索菌群功能改变。计量资料2组间比较采用Wilcoxon秩和检验; 计数资料2组间比较采用χ2检验。得到的菌种和基因功能通路等数据用Shannon系数、Wilcoxon秩和检验和DESeq2进行计算分析,利用Cytoscape将2组的丰富菌种和相关联系直观表现出来。  结果  胆汁淤积组病因包括胆道闭锁11例(26.2%),Citrin蛋白缺乏症4例(9.5%),胆管发育不良4例(9.5%),原因未明23例(54.8%)。2组肠道菌群组成在门水平有显著差异(Z=0.000 046,P<0.05),其中厚壁菌门和拟杆菌门在胆汁淤积组中显著增加; 在种水平上也有差异(Z=0.000 014,P<0.05),胆汁淤积组中有益菌如双歧杆菌明显减少,而潜在致病菌如韦永氏球菌和农研丝杆菌明显增多; 在功能水平上也有差异(Z=0.019 8,P<0.05),胆汁淤积组肠道菌群的功能明显减弱,如氨基酸代谢、糖代谢等。  结论  胆汁淤积婴儿肠道菌群的组成及功能发生改变,胆汁淤积婴儿肠道菌群中有益菌明显减少,潜在致病菌增多,补充双歧杆菌等有益菌可能减少潜在致病菌的产生,从而改变疾病的发展。
  • 图  1  胆汁淤积组和对照组中肠道菌群多样性对比图

    注:a, 门水平上基于Shannon系数计算2组样品菌的丰度分布图; b, KEGG注释后基于Shannon系数计算2组样品菌的功能分布图; c, 种水平上基于Jaccard指数计算2组对比图,黑色为胆汁淤积组,红色为对照组,可见胆汁淤积组联系更紧密; d, 种水平上基于主成分分析按照Rade4软件包描绘的图,胆汁淤积组(黑色)和对照组(红色)可以被分开,提示两组间有显著差异。

    图  2  胆汁淤积组和对照组中排名靠前的菌群组成和功能通路

    注:a, 门水平上排名靠前的菌,纵坐标为所占比例; b,排名靠前的功能通路,纵坐标为所占比例。

    图  3  胆汁淤积组和对照组中较丰富的菌种交互网络图

    注:由Cytoscape展示的交互网络图,农研丝杆菌GR20-10(Niastella koreensis GR20-10)、韦永氏球菌DSM 2008(Veillonella parvula DSM 2008)、加氏乳杆菌ATCC33323(Lactobacillus gasseri ATCC 33323)和沼泽红假单胞菌BisB18(Rhodopseudomonas palustris BisB18)在胆汁淤积组中极为丰富。双歧杆菌(Bifidobacterium)如长双歧杆菌(Bifidobacterium longum)、齿双歧杆菌Bd1(Bifidobacterium dentium Bd1)和短双歧杆菌ACS-071-V-Sch8b(Bifidobacterium breve ACS-071-V-Sch8b)在对照组中极为丰富,狄氏副拟杆菌ATCC 8503(Parabacteroides distasonis ATCC 8503)在对照组中也是较丰富的。

    表  1  2组患儿一般资料比较

    项目 胆汁淤积组(n=42) 对照组(n=32) 统计值 P
    男/女(例) 21/21 25/7 χ2=6.11 0.013
    就诊年龄(d) 90.0(29.0~300.0) 60.0(30.0~120.0) Z=4.88 0.019
    分娩方式[例(%)] χ2=0.03 0.873
      顺产 36(85.7) 27(84.4)
      剖腹产 6(14.3) 5(15.6)
    喂养方式[例(%)] χ2=2.55 0.111
      母乳喂养 34(81.0) 30(93.8)
      人工喂养 8(19.0) 2(6.2)
    TBil(μmol/L) 172.2(41.4~348.9)
    DBil(μmol/L) 78.3(21.4~153.9)
    IBil(μmol/L) 80.4(20.0~241.1)
    胆道闭锁[例(%)] 11(26.2)
    Citrin蛋白缺乏症[例(%)] 4(9.5)
    胆管发育不良[例(%)] 4(9.5)
    原因未明[例(%)] 23(54.8)
    下载: 导出CSV
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  • 收稿日期:  2020-07-05
  • 修回日期:  2020-10-26
  • 刊出日期:  2021-01-18
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