Features of the gut microbiota in patients with severe liver fibrosis and cirrhosis associated with chronic hepatitis C

Objective: to characterize specific changes in the intestinal microbiome profile associated with progressive liver fibrosis in patients with chronic HCV infection

Materials and methods: a single-center cross-sectional clinical study of 88 patients with chronic HCV infection (51 people with chronic viral hepatitis C and 37 people with liver cirrhosis of viral C etiology) was conducted, in which the profile of the gut microbiota was determined by 16S rRNA metagenomic sequencing. High-throughput sequencing was performed using a MiSeq genetic analyzer (Illumina, USA) using a protocol based on the analysis of variable regions of the 16S rRNA gene. The data was analyzed using Kraken2. The significance level is assumed to be 0,05.

Results: significant changes in gut microbial diversity have been described in patients with severe liver fibrosis and cirrhosis. In patients with progressive fibrosis, there was a significant increase in representatives of the Enterobacteriaceae, Lactobacillus, Streptococcus, Enterococcus, Lactococcus and Leuconostoc families. Atypical microorganisms such as Photobacterium, Spiroplasma, Candidatus Portiera are also noted in the gut microbiota. The combination of these changes indicates a shift in microbial equilibrium. On the contrary, in the group of patients without liver fibrosis, there is an increase in the number of Odoribacter and Intestinimonas, which are butyrate producers. As well as Akkermansia and Barnesiella, which indicates the normal functioning of the intestinal microbial community.

Conclusions: changes in the intestinal microbiota in severe fibrosis result in the formation of a stable and self-sustaining pathological microbial community. The identified changes can be used to develop corrective methods aimed at restoring the balance of the intestinal microbiota.

1. Liu Z, Shi O, Zhang T, et al. Disease burden of viral hepatitis A, B, C and E: A systematic analysis. Journal of Viral Hepatitis. 2020;27(12):1284-1296. DOI: https://doi.org/10.1111/jvh.13371

2. Fortea JI, Crespo J, Puente Á. Cirrhosis, a Global and Challenging Disease. J Clin Med. 2022;11(21):6512. DOI: https://doi.org/10.3390/jcm11216512

3. Huang, D.Q., Terrault, N.A., Tacke, F. et al. Global epidemiology of cirrhosis — aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol 20, 388–398 (2023). https://doi.org/10.1038/s41575-023-00759-2

4. Stoma I.O. Mikrobiom v medicine: rukovodstvo dlya vrachej. Moskva; 2024. 320 s.

5. Lee NY, Suk KT. The Role of the Gut Microbiome in Liver Cirrhosis Treatment. International Journal of Molecular Sciences. 2021; 22(1):199. https://doi.org/10.3390/ijms22010199

6. Roehlen N, Crouchet E, Baumert TF. Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells. 2020 Apr 3;9(4):875. doi: 10.3390/cells9040875. PMID: 32260126; PMCID: PMC7226751.

7. Hsu CL, Schnabl B. The gut-liver axis and gut microbiota in health and liver disease. Nat Rev Microbiol. 2023;21(11):719733. DOI: https://doi.org/10.1038/s41579-023-00904-3

8. Izmeneniya kishechnoj mikrobioty na fone hronicheskoj HCV-infekcii v zavisimosti ot genotipa virusa / I. O. Stoma, Z. A. Cejko, E. V. Voropaev [i dr.] // Problemy zdorov’ya i ekologii. – 2025. – T. 22, № 2. – S. 147-160. – DOI 10.51523/27086011.2025-22-2-18. – EDN BWDPSM.

9. Zhang L, Zi L, Kuang T, Wang K, Qiu Z, Wu Z, Liu L, Liu R, Wang P, Wang W. Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study. Front Endocrinol (Lausanne). 2023 Jul 5;14:1159148. doi: 10.3389/fendo.2023.1159148. PMID: 37476494; PMCID: PMC10354516.

10. Li S, Zhou C, Liu T, Zhang L, Liu S, Zhao Q, Liu J, Zhao W. Causal relationships between the gut microbiota, inflammatory cytokines, and alcoholic liver disease: a Mendelian randomization analysis. Front Endocrinol (Lausanne). 2024 Oct 21;15:1442603. doi: 10.3389/fendo.2024.1442603. PMID: 39497803; PMCID: PMC11532067.

11. Baldelli V, Scaldaferri F, Putignani L, Del Chierico F. The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases. Microorganisms. 2021; 9(4):697. https://doi.org/10.3390/microorganisms9040697

12. Taylor, S.J., Winter, M.G., Gillis, C.C. et al. Colonocytederived lactate promotes E. coli fitness in the context of inflammation-associated gut microbiota dysbiosis. Microbiome 10, 200 (2022). https://doi.org/10.1186/s40168-022-01389-7

13. Tuomisto, S., Pessi, T., Collin, P. et al. Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics. BMC Gastroenterol 14, 40 (2014). https://doi.org/10.1186/1471-230X-14-40

14. Jiang L, Wang J, Liu Z, Jiang A, Li S, Wu D, Zhang Y, Zhu X, Zhou E, Wei Z, Yang Z. Sodium Butyrate Alleviates Lipopolysaccharide-Induced Inflammatory Responses by DownRegulation of NF-κB, NLRP3 Signaling Pathway, and Activating Histone Acetylation in Bovine Macrophages. Front Vet Sci. 2020 Nov 5;7:579674. doi: 10.3389/fvets.2020.579674. PMID: 33251265; PMCID: PMC7674777.

15. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucindegrading bacterium. Int J Syst Evol Microbiol. 2004 Sep;54(Pt 5):1469-1476. doi: 10.1099/ijs.0.02873-0. PMID: 15388697.

16. Ubeda C, Bucci V, Caballero S, Djukovic A, Toussaint NC, Equinda M, Lipuma L, Ling L, Gobourne A, No D, Taur Y, Jenq RR, van den Brink MR, Xavier JB, Pamer EG. Intestinal microbiota containing Barnesiella species cures vancomycinresistant Enterococcus faecium colonization. Infect Immun. 2013 Mar;81(3):965-73. doi: 10.1128/IAI.01197-12. Epub 2013 Jan 14. PMID: 23319552; PMCID: PMC3584866.