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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2019, Vol. 13 ›› Issue (02) : 110 -116. doi: 10.3877/cma.j.issn.1674-1358.2019.02.005

所属专题： 文献；

论著

乙型肝炎失代偿期肝硬化患者肠道菌群特征
王艺璇1, 李炜2, 程丹颖2, 刘顺爱3, 张珊2, 韩铭3, 朱琳2, 孙静2, 邢卉春2,†()   
  1. 1. 100015　北京，首都医科大学附属北京地坛医院肝病中心；100015　北京，北京大学地坛教学医院传染病研究所
    2. 100015　北京，首都医科大学附属北京地坛医院肝病中心
    3. 100015　北京，北京大学地坛教学医院传染病研究所
  • 收稿日期:2018-11-16 出版日期:2019-04-15
  • 通信作者: 邢卉春
  • 基金资助:
    北京市医院管理局扬帆计划(No. xmlx201837); "十三五"艾滋病和病毒性肝炎等重大传染病防治(No. 2018ZX10302206-003-006); 吴阶平医学基金会(No. LDWJPMF-103-17001); 首都卫生发展科研专项(No. 2018-2-2173); 北京市医院管理局消化内科学科协同发展中心项目(No. XXT26)

Characteristics of intestinal flora of patients with hepatitis B related decompensated cirrhosis

Yixuan Wang1, Wei Li2, Danying Cheng2, Shun'ai Liu3, Shan Zhang2, Ming Han3, Lin Zhu2, Jing Sun2, Huichun Xing2,†()   

  1. 1. Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Peking University Beijing Ditan Teaching Hospital, Beijing 100015, China
    2. Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
    3. Peking University Beijing Ditan Teaching Hospital, Beijing 100015, China
  • Received:2018-11-16 Published:2019-04-15
  • Corresponding author: Huichun Xing
  • About author:
    Corresponding author: Xing Huichun, Email:
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王艺璇, 李炜, 程丹颖, 刘顺爱, 张珊, 韩铭, 朱琳, 孙静, 邢卉春. 乙型肝炎失代偿期肝硬化患者肠道菌群特征[J/OL]. 中华实验和临床感染病杂志(电子版), 2019, 13(02): 110-116.

Yixuan Wang, Wei Li, Danying Cheng, Shun'ai Liu, Shan Zhang, Ming Han, Lin Zhu, Jing Sun, Huichun Xing. Characteristics of intestinal flora of patients with hepatitis B related decompensated cirrhosis[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2019, 13(02): 110-116.

目的

观察乙型肝炎失代偿期肝硬化患者肠道菌群特征。

方法

收集首都医科大学附属北京地坛医院收治的符合入排标准的乙型肝炎失代偿期肝硬化患者及健康者粪便标本共82例，其中乙型肝炎失代偿期肝硬化且不合并其他感染者41例和健康对照者41例。所有标本均进行细菌16S rDNA高通量测序，并用Qiime软件、R软件以及LEfSe软件分析菌群构成、丰度和差异性等特征，同时分析两组研究对象肝硬化生态失调比值的差异。

结果

乙型肝炎失代偿期肝硬化组患者粪便菌群丰度及多样性较健康对照组显著降低，Weighted Unifrac的Beta多样性分析显示两组研究对象肠道菌群结构差异有统计学意义（P = 0.004）。门水平方面，乙型肝炎失代偿期肝硬化组患者厚壁菌门丰度较健康对照组显著降低（Z =－2.57、P = 0.045）。属水平方面，乙型肝炎失代偿期肝硬化患者组链球菌属、梭杆菌属、韦荣球菌属和嗜血杆菌属丰度较健康对照组显著增加（P均< 0.05）；毛螺菌属、Dorea、Dialister、Subdoligranulum丰度较健康对照组显著降低（P均< 0.05）。使用LEfSe软件比较两组人群菌群差异及其功能，发现两组间具有显著差异的菌群生物学指标有乳杆菌目、梭菌目毛螺菌科及瘤胃菌科（LDA > 4）。

结论

乙型肝炎失代偿期肝硬化且不合并感染者的肠道菌群多样性显著降低、厚壁菌门相对丰度显著降低，存在显著的肠道菌群失衡，但菌群失衡程度较轻，涉及显著变化的菌属较少。

关键词: 肝炎，乙型, 失代偿肝硬化, 肠道菌群
Objective

To investigate the characteristics of intestinal flora of patients with hepatitis B related decompensated cirrhosis.

Methods

Total of 82 fecal specimens were collected from patients with hepatitis B related decompensated cirrhosis and healthy persons in Beijing Ditan Hospital, Capital Medical University, including 41 patients with hepatitis B related decompensated cirrhosis without other infection and 41 healthy controls. All samples were sequenced by 16S rDNA high-throughput sequencing. The composition, abundance and difference of bacterial flora were analyzed by Qiime, R and LEfSe softwares, while the difference of ecological imbalance ratio between the two groups was also analyzed.

Results

The abundance and diversity of fecal microflora of hepatitis B related decompensated cirrhosis group were significantly lower than that of healthy control group. The Beta diversity analysis of Weighted Unifrac showed that there was significant difference in intestinal microflora composition between the two groups (P = 0.004). On phylum level, the abundance of firmicutes was significantly decreased in hepatitis B related decompensated cirrhosis group (Z =-2.57, P = 0.045). On genus level, the abundance of Streptococcus, Fusobacterium, Veillonella, and Haemophilus were significantly increased in hepatitis B related decompensated cirrhosis group (all P < 0.05). While Lachnospira, Dorea, Dialister and Subdoligranulum were significantly decreased (all P < 0.05). LEfSe was used to compare the difference of flora and its function between the two groups. It was found that the biological indexes of Firmicutes Bacilli Lactobacillales, Clostridiales Lachnospira and Ruminococcaceae in both groups were significantly different (LDA > 4).

Conclusions

The diversity of intestinal flora and the relative abundance of thick-walled bacteria in patients with hepatitis B related decompensated cirrhosis without other infection were significantly decreased, and there was a significant imbalance of intestinal flora, but the degree of imbalance was mild and the number of bacteria with significant variation was less.

Key words: Hepatitis B, Decompensated cirrhosis, Gut microbiome
表1 健康对照组与乙型肝炎失代偿期肝硬化组患者的一般资料
组别 例数 年龄（± s，岁） 性别（男/女，例） BMI （± s） ALT [M（P25，P75），U/L）] AST（U/L） [M（P25，P75），U/L）]
健康对照组 41 32 ± 6 15/26 21.5 ± 1.6 12（10.8，26.5） 19（16.2，21.3）
乙型肝炎失代偿期肝硬化组 41 42 ± 9 23/18 22.2 ± 1.1 23（18.7，36.7） 33（22.1，49.2）
统计量 ? t = 8.49 χ2 = 3.13 t = 1.06 Z = 3.29 Z = 5.43
P值 ? 0.038 0.080 0.060 0.001 < 0.001
组别 例数 ALB [M（P25，P75），g/L] 总胆红素[M（P25，P75），μmol/L] INR [M（P25，P75）] MELD评分[M（P25，P75），分]
健康对照组 41 47（45.4，49.6） 12（8.8，15.8） — —
乙型肝炎失代偿期肝硬化组 41 36（31.2，40.7） 22（13.5，31.6） 1.2（1.1，1.4） 7.8 ± 4.9
统计量 ? Z =－6.80 Z = 4.26 — —
P值 ? < 0.001 < 0.001 — —
图1 健康对照组和乙型肝炎失代偿期肝硬化患者粪便微生物群多样性变化
图2 乙型肝炎失代偿期肝硬化患者与健康对照存在显著差异的菌属
图3 基于Weighted Unifrac的Beta多样性分析及LEfSe进化图
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