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

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.