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肝移植对胆道闭锁儿童肠道菌群的影响

宋伟 孙丽莹 朱志军 魏林 曲伟 曾志贵

宋伟, 孙丽莹, 朱志军, 等. 肝移植对胆道闭锁儿童肠道菌群的影响[J]. 器官移植, 2021, 12(6): 692-699. doi: 10.3969/j.issn.1674-7445.2021.06.008
引用本文: 宋伟, 孙丽莹, 朱志军, 等. 肝移植对胆道闭锁儿童肠道菌群的影响[J]. 器官移植, 2021, 12(6): 692-699. doi: 10.3969/j.issn.1674-7445.2021.06.008
Song Wei, Sun Liying, Zhu Zhijun, et al. Effect of liver transplantation on intestinal microflora in children with biliary atresia[J]. ORGAN TRANSPLANTATION, 2021, 12(6): 692-699. doi: 10.3969/j.issn.1674-7445.2021.06.008
Citation: Song Wei, Sun Liying, Zhu Zhijun, et al. Effect of liver transplantation on intestinal microflora in children with biliary atresia[J]. ORGAN TRANSPLANTATION, 2021, 12(6): 692-699. doi: 10.3969/j.issn.1674-7445.2021.06.008

肝移植对胆道闭锁儿童肠道菌群的影响

doi: 10.3969/j.issn.1674-7445.2021.06.008
基金项目: 

国家自然科学基金 81570586

详细信息
    作者简介:

    宋伟,女,1992年生,博士研究生,研究方向为消化内科,Email: 25702018222@qq.com

    通讯作者:

    孙丽莹,女,1967年生,主任医师,博士研究生导师,研究方向为肝移植感染与免疫,Email: sunxlx@outlook.com

  • 中图分类号: R617, R575

Effect of liver transplantation on intestinal microflora in children with biliary atresia

More Information
  • 摘要:   目的  研究肝移植对胆道闭锁儿童肠道菌群的影响。  方法  收集16例胆道闭锁儿童肝移植术前、术后6个月的粪便样本及肝功能指标等临床数据,10名健康儿童作为健康对照组。对粪便样本进行DNA提取和宏基因组测序,采用R语言等软件包进行数据分析。分析肝移植术后肠道菌群物种结构及功能组成的改变情况,检测胆道闭锁儿童肝移植术后肠道菌群恢复的程度,分析肠道菌群与肝功能指标间的关系。  结果  肝移植术后,胆道闭锁儿童肠道菌群的物种数量增加。胆道闭锁儿童肝移植术前肠道菌群以机会致病菌为主,移植术后机会致病菌丰度下降,产短链脂肪酸菌丰度升高(均为P < 0.05)。肝移植术后,脂代谢、氨基酸代谢、碳水化合物代谢、能量代谢、辅助因子和维生素代谢等代谢通路增强,而细菌感染、免疫系统疾病、药物抵抗等相关代谢通路减弱。与健康对照组比较,肝移植术后组肠道菌群多样性和菌群结构差异均无统计学意义,但两组间仍存在差异物种。胆道闭锁儿童肝移植术后肝功能指标均呈下降趋势(均为P < 0.000 1)。肠道有益菌的丰度与肝功能指标呈负相关,而机会致病菌丰度与肝功能指标呈正相关(均为P < 0.05)。  结论  肝移植在一定程度上可以显著改善胆道闭锁儿童肠道菌群的结构及功能组成。

     

  • 图  1  肝移植术前组和肝移植术后组肠道菌群物种数量的韦恩图(属水平)

    Figure  1.  Venn diagram of the number of intestinal microflora species in the pre- and post-liver transplant group(genus level)

    图  2  肝移植术前组和肝移植术后组肠道菌群基因数量比较及相关性分析

    注:A图为肝移植术前组和肝移植术后组基因数量比较;B图为两组基因间的Spearman相关性分析(仅显示P < 0.05的结果)。

    Figure  2.  Comparison and correlation analysis of the number of intestinal microflora genes in the pre- and post-liver transplant group

    图  3  肝移植术前组和肝移植术后组肠道菌群功能代谢通路比较

    Figure  3.  Comparison of functional metabolic pathways of intestinal microflora between the pre- and post-liver transplant group

    图  4  肝移植术后组与健康对照组肠道菌群多样性和菌群结构比较

    注:A图为肝移植术后组与健康对照组肠道菌群α多样性比较;B图为肝移植术后组与健康对照组肠道菌群β多样性比较,横纵坐标的刻度为相对距离,无实际意义,PCoA1表示尽可能最大解释数据变化的主坐标成分,PCoA1(a%)表示第一主坐标所占比例为a%,PCoA2表示剩余的变化度中占比例最大的主坐标成分。

    Figure  4.  Comparison of intestinal microflora diversity and structure between post-liver transplant group and healthy control group

    图  5  肝移植术后组与健康对照组差异物种比较

    Figure  5.  Comparison of species between post-liver transplant group and healthy control group

    图  6  肠道菌群与肝功能指标的相关性分析热图

    注:图中颜色的深浅直观展示物种与肝功能指标的相关性大小,蓝色代表正相关,红色代表负相关,*为P < 0.05,+为P < 0.01。

    Figure  6.  Heat map of correlation analysis between intestinal microflora and liver function indexes

    表  1  肝移植术前组和肝移植术后组丰度发生改变的物种(属水平)

    Table  1.   Species with altered abundance in the pre- and post-liver transplant group(genus level)

    物种名称 肝移植术后组(n=16) 肝移植术前组(n=16) P 富集组
    g__Enterobacter 0.000 940 0 0.007 170 0 0.040 术前
    g__Yersinia 0.000 039 0 0.000 325 0 0.030 术前
    g__Morganella 0.000 017 0 0.000 090 0 0.010 术前
    g__Serratia 0.000 017 0 0.000 038 0 0.040 术前
    g__Blautia 0.004 100 0 0.000 058 0 0.003 术后
    g__Clostridium 0.003 050 0 0.000 400 0 0.007 术后
    g__Eubacterium 0.001 200 0 0.000 030 0 0.002 术后
    g__Roseburia 0.000 380 0 0.000 010 0 0.001 术后
    g__Akkermansia 0.000 007 0 0.000 000 9 0.030 术后
    下载: 导出CSV

    表  2  肝移植术前组和肝移植术后组肝功能指标比较

    Table  2.   Comparison of liver function indexes between pre- and post-liver transplant group[M(Q25, Q75)]

    肝功能指标 肝移植术前组(n=16) 肝移植术后组(n=16) P
    ALT(U/L) 151(62,181) 21(17,33) < 0.000 1
    AST(U/L) 212(107,272) 36(27,40) < 0.000 1
    ALP(U/L) 611(434,833) 249(204,329) < 0.000 1
    GGT(U/L) 181(106,532) 17(14,33) < 0.000 1
    TBA(μmol/L) 164(88,284) 9(5,13) < 0.000 1
    TB(μmol/L) 281(8,557) 8(5,10) < 0.000 1
    下载: 导出CSV
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  • 收稿日期:  2021-08-26
  • 刊出日期:  2021-11-15

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