Microbiota and Long-Term Prognosis in Liver Cirrhosis

Abstract

   Purpose. To compare the gut microbiota in patients with an anamnesis of liver cirrhosis of less than and more than 10 years.   Materials and methods. A one-stage study and metagenomic fecal sequencing of 40 hospitalized patients with liver cirrhosis were conducted, of which 35 were with a history of cirrhosis of less than 10 years and 5 — more than 10 years. High-throughput sequencing was performed using a MiSeq genetic analyzer (Illumina, USA) and a protocol based on analysis of 16s rRNA gene variable regions. The study was registered in Clinicaltrials.gov (NCT05335213). Data analysis was performed using Kraken2 algorithm. The analysis of the difference in the proportional composition of the microbiome between the groups was carried out using polynomial Dirichlet modeling (Likelihood-Ratio-Test Statistics: Several Sample Dirichlet-Multinomial Test Comparison), the Mann-Whitney test with preliminary data transformation by CLR transformation (Centered log ratio transform), differential analysis of gene expression based on negative binomial distribution (DESeq2). The significance level α assumed to be 0.05.   Results. In patients with liver cirrhosis, the dominant phylotypes of fecal microbiota are Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, minor components include taxa Aquificae, Coprothermobacterota, Tenericutes, Verrucomicrobia, Chloroflexi, Deinococcus-Thermus, Thermotogae, Chlorobi. Significant differences have been established in the density of dominant and minor philotypes of gut bacteria, such as Actinobacteria, Proteobacteria, Tenericutes, Coprothermobacterota, as well as some classes, genera, bacterial species in patients with different disease duration (p < 0.05).   Conclusion. There is no doubt about the effect of gut microbiota on compensation for liver function. The established differences in the composition of the microbiota in patients with liver cirrhosis depending on survival over 10 years are of scientific and practical importance for the formation of an evidence-based approach to the use of microbiome-associated interventions