肝硬化患者肠道菌群失调的特征及驱动因子分析

郭晓霞; 胡娜; 廉晓晓; 孙元培; 李玉珍; 吕蕾; 叶永安; 李小科

doi:10.3969/j.issn.1001-5256.2020.07.016

肝硬化患者肠道菌群失调的特征及驱动因子分析

DOI: 10.3969/j.issn.1001-5256.2020.07.016

1. 山西省中医药研究院
2. 山西中医药大学
3. 北京中医药大学东直门医院

基金项目:

山西省重点研发计划项目(201603D321042)；北京中医药大学东直门医院中医内科学教育部重点实验室开放基金项目(2016-ZDSYSKFJJ-08)；

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中图分类号: R575.2
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出版历程
- 出版日期: 2020-07-20

Features of intestinal flora imbalance in patients with liver cirrhosis and related driving factors

1. Shanxi Research Institute of Traditional Chinese Medicine, Taiyuan 030012, China
2. Shanxi University of Chinese Medicine, Taiyuan 030024, China
3. Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

Research funding:

摘要

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 r DNA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...
- 肝硬化 /
- 胃肠道微生物组 /
- 驱动蛋白
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 from10 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 16 S 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 and0. 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.
- liver cirrhosis /
- gastrointestinal microbiome /
- kinesin

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