首 页   本刊简介  编委会  审稿专家  在线期刊  写作规范  广告合作  联系我们
您现在的位置:首页 => 在线期刊 => 2020年 7期“炎症性肠病与肝胆胰疾病” => 肝纤维化及肝硬化 =>肝硬化患者肠道菌群失..
肝硬化患者肠道菌群失调的特征及驱动因子分析
Features of intestinal flora imbalance in patients with liver cirrhosis and related driving factors
文章发布日期:2020年07月09日  来源:  作者:郭晓霞,胡娜,廉晓晓,等  点击次数:245次  下载次数:49次

调整字体大小:

(此处下载失败可以在在线预览处保存副本或者右键另存为)

【摘要】:目的 研究肝硬化患者肠道菌群分布特征,并分析影响群落变异的驱动因子,评价其与肝硬化严重程度的相关性。方法 收集2017年8月-2019年8月山西省中医院招募的10例健康志愿者与70例肝硬化患者的血液和粪便标本进行检验。根据细菌16S rDNA高通量测序获得肝硬化患者肠道菌群的差异菌属。符合正态分布的计量资料组间比较采用单因素方差分析;非正态分布的计量资料组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。相关性分析采用Spearman检验。并用CANOCO5.0软件进行RDA分析临床指标与肠道群落变异的相关性。结果 肝硬化患者肠道菌群的种类发生了特异性变化,与健康对照组相比,有81个OTU是肝硬化患者肠道菌群宏基因组中特有的,其中ALBI 1级、2级、3级分别独有39、34、8个OTU。随着肝硬化疾病发展,Chao1、ACE指数明显减少(H值分别为8.111、9.112,P值分别为0.044、0.028),且与ALBI分级呈显著负相关(r值分别为-0.287、-0.297,P值分别为0.016、0.012)。与健康对照组相比,肝硬化患者中的肠道菌群失调以罗斯氏菌属、韦荣球菌属、链球菌属和嗜血杆菌属4种致病菌增多,粪球菌属和梭菌属2种有益菌减少为特征(H值分别为15.96、13.01、8.94、11.09、13.07、16.27,P值均<0.05)。2种有益菌间呈正相关(P<0.05),四种致病菌间呈正相关(P<0.001),有益菌粪球菌属与四种致病菌之间呈显著负相关(P<0.001)。差异菌属与临床指标进行相关性分析,有益菌粪球菌属与Alb呈正相关(r=0.273,P=0.022),与PT、ALBI评分呈负相关(r值分别为-0.300、-0.263,P值分别为0.011、0.028);致病菌罗斯氏菌属、韦荣球菌属、链球菌属、嗜血杆菌属均与Alb呈负相关,与PT、TBil、ALBI评分呈正相关(P值均<0.05)。RDA分析显示PT、TBil、AST与肠道菌群分布相关性较大,其中PT对群落变异的影响最具有显著性(P=0.002)。健康对照组、ALBI 1级、ALBI 2级、ALBI 3级的CDIG分别为2.58、0.76、0.24、0.04,差异具有统计学意义(H=16.750,P<0.001 ),CDIG与TBil、PT及ALBI呈显著负相关(r值分别为-0.313、-0.323、-0.366, P值分别为0.008、0.006、0.002)。结论 肝硬化患者存在菌群失调的主要特征为致病菌的过度增长协同有益菌的缺乏及各菌属之间的比例失调;PT是驱动肠道菌群落变异的主要因子;CDIG可反映肝硬化患者肠道菌群失衡程度,CDIG越小,肝硬化程度越严重。
【Abstract】:Objective To investigate the distribution characteristics of intestinal flora in patients with liver cirrhosis, the driving factors for intestinal flora variation, and their association with the severity of liver cirrhosis. Methods Blood and stool specimens were collected from 10 healthy volunteers and 70 patients with liver cirrhosis who were recruited by Shanxi Provincial Hospital of Traditional Chinese Medicine from August 2017 to August 2019. High-throughput sequencing of bacterial 16S rDNA was performed to identify differentially expressed bacterial genera in intestinal flora of patients with liver cirrhosis. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed, and CANOCO5.0 software was used to perform RDA analysis to investigate the association of clinical indices with intestinal flora variation. Results Specific changes were observed in the species of intestinal flora in patients with liver cirrhosis, and compared with the healthy control group, the patients with liver cirrhosis had 81 unique operational taxonomic units (OTUs) in the metagenome of intestinal flora, among which there were 39 albumin-bilirubin (ALBI) grade 1 OTUs, 34 ALBI grade 2 OTUs, and 8 ALBI grade 3 OTUs. With the progression of liver cirrhosis, there were significant reductions in Chao1 index and ACE index (H=8.111 and 9.112, P=0.044 and 0.028), which were significantly negatively correlated with ALBI grade (r=-0.287 and -0.297, P=0.016 and 0.012). Compared with the healthy control group, the patients with liver cirrhosis had significant increases in four genera of pathogenic bacteria (Roseburia, Veillonella, Streptococcus, and Haemophilus) and significant reductions in two genera of probiotic bacteria (Coprococcus and Clostridium) as the main features of intestinal flora imbalance (H=15.96, 13.01, 8.94, 11.09, 13.07, and 16.27, all P<0.05). There was a positive correlation between the two genera of probiotic bacteria (P<0.05) and the four genera of pathogenic bacteria (P<0.001), while Coprococcus of probiotic bacteria was negatively correlated with the four genera of pathogenic bacteria (P<0.001). The correlation analysis of the differentially expressed genera and clinical indices showed that Coprococcus of probiotic bacteria was positively correlated with albumin (Alb) (r=0.273, P=0.022) and negatively correlated with prothrombin time (PT) and ALBI score (r=-0.300 and -0.263, both P<0.05); the pathogenic bacteria Rossella, Veillonella, Streptococcus, and Haemophilus were negatively correlated with Alb and positively correlated with PT, total bilirubin (TBil), ALBI score (all P<0.05). The RDA analysis showed that PT, TBil, and aspartate aminotransferase were highly correlated with the distribution of intestinal flora, among which PT had the most significant effect on intestinal flora variation (P=0.002). In the healthy control group, ALBI grade 1/2/3 OTUs had a cirrhosis dysbiosis index of genus (CDIG) of 2.58, 0.76, 0.24, and 0.04, respectively (H=16.750, P<0.001), and CDIG was negatively correlated with TBil, PT, and ALBI (r=-0.313, -0.323, and -0.366, P=0.008, 0.006, and 0.002). Conclusion Excessive growth of pathogenic bacteria, a lack of probiotic bacteria, and the ratio imbalance between various bacterial genera are the main characteristics of intestinal flora imbalance in patients with liver cirrhosis, and PT is the main driving factor for intestinal flora variation. CDIG can reflect the degree of intestinal flora imbalance in patients with liver cirrhosis, and the severity of liver cirrhosis increases with the reduction in CDIG.
【关键字】:肝硬化; 胃肠道微生物组; 驱动蛋白
【Key words】:liver cirrhosis; gastrointestinal microbiome; kinesin
【引证本文】:GUO XX, HU N, LIAN XX, et al. Features of intestinal flora imbalance in patients with liver cirrhosis and related driving factors[J]. J Clin Hepatol, 2020, 36(7): 1527-1533. (in Chinese)
郭晓霞, 胡娜, 廉晓晓, 等. 肝硬化患者肠道菌群失调的特征及驱动因子分析[J]. 临床肝胆病杂志, 2020, 36(7): 1527-1533.

地址:长春市东民主大街519号《临床肝胆病杂志》编辑部 邮编:130061 电话:0431-88782542/3542
临床肝胆病杂志 版权所有 Copyright © 2009 - 2013 Lcgdbzz.org. All Rights Reserv 吉ICP备10000617号

吉公网安备 22010402000041号