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轻微肝性脑病患者经颈静脉肝内门体分流术后不同预后组肠道菌群的变化

李萌浩 李凯 汤世豪 王钲钰 郭文刚 殷占新 韩国宏

李萌浩, 李凯, 汤世豪, 等. 轻微肝性脑病患者经颈静脉肝内门体分流术后不同预后组肠道菌群的变化[J]. 临床肝胆病杂志, 2021, 37(2): 326-330. DOI: 10.3969/j.issn.1001-5256.2021.02.016
引用本文: 李萌浩, 李凯, 汤世豪, 等. 轻微肝性脑病患者经颈静脉肝内门体分流术后不同预后组肠道菌群的变化[J]. 临床肝胆病杂志, 2021, 37(2): 326-330. DOI: 10.3969/j.issn.1001-5256.2021.02.016
LI MH, LI K, TANG SH, et al. Changes in gut microbiota after transjugular intrahepatic portosystemic shunt in cirrhotic patients with mild hepatic encephalopathy in different prognosis groups[J]. J Clin Hepatol, 2021, 37(2): 326-330. DOI: 10.3969/j.issn.1001-5256.2021.02.016
Citation: LI MH, LI K, TANG SH, et al. Changes in gut microbiota after transjugular intrahepatic portosystemic shunt in cirrhotic patients with mild hepatic encephalopathy in different prognosis groups[J]. J Clin Hepatol, 2021, 37(2): 326-330. DOI: 10.3969/j.issn.1001-5256.2021.02.016

轻微肝性脑病患者经颈静脉肝内门体分流术后不同预后组肠道菌群的变化

DOI: 10.3969/j.issn.1001-5256.2021.02.016
基金项目: 

国家自然科学基金 81420108020

详细信息
    作者简介:

    李萌浩(1997—),男,博士,主要从事肠道菌群与肝硬化门静脉高压并发症方面的研究

    通讯作者:

    韩国宏,hangh@fmmu.edu.cn

  • 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:韩国宏教授负责课题设计;李萌浩、汤世豪、李凯、王钲钰、郭文刚和殷占新参与收集数据;李萌浩进行资料分析和撰写论文;李凯副主任医师和韩国宏教授指导撰写文章,修改论文并最后定稿。
  • 中图分类号: R575.2

Changes in gut microbiota after transjugular intrahepatic portosystemic shunt in cirrhotic patients with mild hepatic encephalopathy in different prognosis groups

  • 摘要:   目的  对比分析肝硬化轻微肝性脑病(MHE)患者经颈静脉肝内门体分流术(TIPS)后不同预后组肠道菌群结构与术前的差异。  方法  选取2016年7月—2017年7月西京医院消化病院住院并接受TIPS治疗的28例MHE患者,分别于术前1~3 d和术后1个月收集粪便样本及采样时临床资料信息,根据术后预后不同分为3组:无HE组(n=8)、MHE组(n=12)和显性脑病(OHE)组(n=8)。对粪便样本采取16S rRNA高通量测序技术进行测序得到菌群相对丰度并在属水平使用SPSS和R语言对各组间菌群物种多样性,术后变化和变化差异展开分析。计数资料组间比较采用χ2检验,计量资料3组间比较采用Kruskal-Wallis H检验,采用Bonferroni法进行多个样本的多重比较,同组患者术前术后的比较采用Wilcoxo符号秩检验。微生物组Beta分析基于Bray Curtis距离矩阵进行主坐标分析(PCoA),使用Adonis法(PerMANOVA)对比组间差异。  结果  基于Bray Curtis距离矩阵的PCoA分析显示,仅MHE组术前和术后的beta多样性明显改变(F=2.71,P=0.049)。术后无HE组原生菌群小杆菌属、粪球菌属、瘤胃菌科某属、解黄酮菌属和狭义梭菌属丰度较术前明显升高(Z值分别为2.521、2.1、2.1、2.1和1.96,P值均<0.05);MHE组术后有害菌群颗粒链菌属(Z=2.521, P=0.012)、肠球菌属(Z=2.51, P=0.012)、链球菌属(Z=2.432, P=0.015)和罗氏菌属(Z=2.001, P=0.045)丰度较术前明显下降,但韦荣球菌属(Z=2.353, P=0.019)和巨球菌属(Z=1.955, P=0.05)丰度却明显上升; OHE组术后仅观察到韦荣球菌属丰度较术前升高(Z=2.38,P= 0.017)。3组间菌群变化量(术后丰度/术前丰度)比较差异有统计学意义[无HE组vs MHE组vs OHE组:2.00(1.11~91.61) vs 1.21(0.26~6.79) vs 0.09(0.01~0.92),χ2=6.249,P=0.043]。  结论  TIPS术后不同预后患者肠道菌群的变化有明显的差异,原生菌群丰度的升高可能对缓解HE病情有一定影响。
  • 图  1  MHE组患者术前术后菌群beta多样性对比分析

    注:基于Bray Curtis距离矩阵的主坐标分析,MHE组术前术后beta多样性有统计学差异(F=2.71,P=0.049)。

    图  2  不同预后组TIPS术前术后肠道菌群变化情况

    图  3  不同预后组TIPS术后粪球菌属变化量比较

    注:3组间菌群变化量有明显差异(χ2=6.249,P=0.043),球菌属变化量在无HE组和MHE组中均明显高于OHE组(P值分别为0.021、0.050),而无HE组与MHE组差异无统计学意义(P>0.05)。

    表  1  不同预后组术前基线特征比较

    指标 无HE组(n=8) MHE组(n=12) OHE组(n=8) χ2 P
    年龄(岁) 49.5(45.8~52.8) 54.5(49.8~59.5) 46.5(44.3~52.8) 5.28 0.07
    性别[男,例(%)] 3(37.5) 6(50.0) 4(50.0) 3.08 0.61
    BMI(kg/m2) 18.7(18.3~20.7) 21.6(18.6~24.1) 21.4(19.6~23.8) 4.43 0.11
    肝硬化病因[HBV,例(%)] 4(50.0) 7(58.3) 7(87.5) 7.39 0.35
    MELD评分 10.9(7.8~13.2) 13.4(10.0~17.5) 13.4(12.7~14.9) 4.82 0.10
    Child-Pugh分级[例(%)] 2.44 0.49
      A(5~6) 4(50.0) 3(12.5) 2(25.0)
      B(7~9) 4(50.0) 6(50.0) 5(62.5)
      C(10~13) 0(0) 3(12.5) 1(12.5)
    INR 1.4(1.1~1.6) 1.4(1.2~1.9) 1.6(1.5~1.7) 4.92 0.10
    血红蛋白(g/dl) 80.0(75.5~83.8) 87.0(79.3~94.3) 80.0(59.0~92.0) 1.69 0.43
    总蛋白(mg/dl) 68.2(53.1~73.9) 68.0(55.7~78.9) 66.2(54.7~68.0) 0.83 0.66
    Alb(g/dl) 36.5(30.6~39.3) 34.4(28.1~37.2) 32.7(31.4~35.5) 1.10 0.58
    TBil(μmol/L) 15.2(10.6~20.6) 23.6(14.7~49.6) 28.1(20.4~36.1) 4.86 0.09
    AST(U/L) 21.5(13.0~40.3) 21.0(11.3~30.0) 28.5(20.3~34.8) 1.77 0.41
    ALT(U/L) 30.5(20.8~42.8) 27.5(21.0~42.5) 31.0(21.5~37.5) 0.01 0.99
    ALP(U/L) 97.0(73.8~117.0) 65.5(49.8~92.8) 79.0(59.8~112.3) 3.69 0.16
    γ-氨基丁酸(U/L) 32.0(21.0~45.8) 23.5(14.0~56.5) 31.0(20.0~49.0) 0.63 0.73
    肌酐(mg/dl) 77.5(66.5~93.8) 85.5(73.0~105.0) 72.0(68.3~95.0) 1.46 0.48
    静脉血氨(μg/dl) 51.0(21.0~60.0) 37.5(23.8~60.5) 36.0(27.5~47.5) 0.29 0.86
    注:MELD,终末期肝病模型。
    下载: 导出CSV

    表  2  不同预后组术前alpha多样性比较

    多样性指数 无HE组(n=8) MHE组(n=12) OHE组(n=8) χ2 P
    Ace指数 186.70(137.96~232.29) 214.69(144.20~354.14) 186.68(130.79~241.34) 0.96 0.62
    Chao1指数 194.64(133.60~215.46) 203.40(138.58~352.64) 183.79(118.53~208.50) 1.03 0.60
    Shannon指数 2.65(2.02~3.12) 2.95(2.56~3.95) 2.67(2.04~3.50) 1.71 0.43
    Simpson指数 0.16(0.09~0.23) 0.09(0.05~0.16) 0.13(0.07~0.26) 2.46 0.29
    下载: 导出CSV
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  • 收稿日期:  2020-09-13
  • 修回日期:  2020-09-30
  • 刊出日期:  2021-02-20
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