Changes in the intestinal microbiota with a background of chronic HCV infection, depending on the genotype of the virus

Objective. To characterize the intestinal microbial diversity in patients with chronic hepatitis C virus infection, depending on the HCV genotype.

Materials and methods. A cohort single-center study of 41 patients with chronic HCV infection (32 people with chronic viral hepatitis C and 9 people with liver cirrhosis of viral C etiology) was conducted, within which the intestinal microbiota profile was determined by the method of metagenomic sequencing of 16S rRNA. High-throughput sequencing was performed using the MiSeq genetic analyzer (Illumina, USA) using a protocol based on the analysis of variable regions of the 16S rRNA gene. The data were analyzed using the Kraken2 algorithm. The significance level was taken to be 0.05.

Results. The microbial diversity of the intestines of patients with HCV has been characterized depending on the HCV genotype. Differences in the abundance of Actinomycetota and Verrucomicrobiota have been established at the type level. A number of Actinomycetota in patients with HCV genotype 3 was more than 3 times higher than in patients with HCV genotype 1. The Verrucomicrobiota type was significantly higher in patients with HCV genotype 1 than in patients with HCV genotype 3. At the class level, significant differences were found in the abundance of Actinomycetia, Verrucomicrobiia, Bacteroidia, Mollicutes, and Gammaproteobacteria. Significant changes at the family and genus levels are described.

Conclusion. For the first time, microbial diversity of the intestine in patients with chronic hepatitis C virus infection has been characterized depending on the HCV genotype. Further research will help to better understand the pathogenetic mechanisms of HCV infection, which will contribute to the development of personalized approaches in the treatment of patients with chronic viral liver disease.

1. Liu Z, Shi O, Zhang T, Jin L, Chen X. 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. Stoma IO. Microbiome in medicine: a guide for doctors. Moscow: GEOTAR-Media, 2024. 320 p. [date of access 2025 April 11]. Available from: https://www.rosmedlib.ru/book/ISBN9785970486764.html?SSr=07E903064283A (in Russ.).

4. Lee NY, Suk KT. The Role of the Gut Microbiome in Liver Cirrhosis Treatment. Int J Mol Sci. 2020;22(1):199. DOI: https://doi.org/10.3390/ijms22010199

5. Acharya C, Bajaj JS. Chronic Liver Diseases and the Microbiome-Translating Our Knowledge of Gut Microbiota to Management of Chronic Liver Disease. Gastroenterology. 2021;160(2):556-572. DOI: https://doi.org/10.1053/j.gastro.2020.10.056

6. Sehgal R, Bedi O, Trehanpati N. Role of Microbiota in Pathogenesis and Management of Viral Hepatitis. Front Cell Infect Microbiol. 2020;10:341. DOI: https://doi.org/10.3389/fcimb.2020.00341

7. Tseiko ZA. Chronic HCV infection: clinical and laboratory characteristics at the present stage. Clinical infectology and parasitology. 2025;14(1):115-124. (In Russ.). DOI: https://doi.org/10.34883/PI.2025.14.1.048

8. Hsu CL, Schnabl B. The gut-liver axis and gut microbiota in health and liver disease. Nat Rev Microbiol. 2023;21(11):719-733. DOI: https://doi.org/10.1038/s41579-023-00904-3

9. El-Mowafy M, Elgaml A, El-Mesery M, Sultan S, Ahmed TAE, Gomaa AI, Aly M, Mottawea W. Changes of Gut-Microbiota-Liver Axis in Hepatitis C Virus. Infection. Biology (Basel). 2021;10(1):55. DOI: https://doi.org/10.3390/biology10010055

10. Dempsey E, Corr SC. Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives. Front Immunol. 2022;13:840245. DOI: https://doi.org/10.3389/fphar.2022.1042189

11. Pinzone MR, Celesia BM, Di Rosa M, Cacopardo B, Nunnari G. Microbial translocation in chronic liver diseases. Int J Microbiol. 2012;2012:694629. DOI: https://doi.org/10.1155/2012/694629

12. Zhang N, Zhu W, Zhang S, Liu T, Gong L, Wang Z, et al. Novel Bifidobacterium/Klebsiella Ratio in Characterization Analysis of the Gut and Bile Microbiota of CCA Patients. Microb Ecol. 2023;87(1):5. DOI: https://doi.org/10.1155/2012/694629

13. Walterson AM, Stavrinides J. Pantoea: insights into a highly versatile and diverse genus within the Enterobacteriaceae. FEMS Microbiol Rev. 2015;39(6):968-984. DOI: https://doi.org/10.1093/femsre/fuv027

14. Yang J, Ma Y, Tan Q, Zhou B, Yu D, Jin M, et al. Gut Streptococcus is a microbial marker for the occurrence and liver metastasis of pancreatic cancer. Front Microbiol. 2023;14:1184869. DOI: https://doi.org/10.3389/fmicb.2023.1184869

15. Yang Y, Song X, Wang G, Xia Y, Xiong Z, Ai L. Understanding Ligilactobacillus salivarius from Probiotic Properties to Omics Technology. A Review. Foods. 2024;13(6):895. DOI: https://doi.org/10.3390/foods13060895

16. Wu C, Yang F, Zhong H, Hong J, Lin H, Zong M, et al. Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption. Cell Host Microbe. 2024;32(8):1301-1314.e9. DOI: https://doi.org/10.1016/j.chom.2024.06.012

17. West SR, Suddaby AB, Lewin GR, Ibberson CB. Rothia. Trends Microbiol. 2024;32(7):720-721. DOI: https://doi.org/10.1016/j.tim.2024.03.009

18. Teixeira CG, Fusieger A, Milião GL, Martins E, Drider D, Nero LA, de Carvalho AF. Weissella: An Emerging Bacterium with Promising Health Benefits. Probiotics Antimicrob Proteins. 2021;13(4):915-925. DOI: https://doi.org/10.1007/s12602-021-09751-1

19. Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007;20(4):593-621. DOI: https://doi.org/10.1128/CMR.00008-07

20. Magdy Wasfy R, Abdoulaye A, Borentain P, Mbaye B, Tidjani Alou M, et al. Thomasclavelia ramosa and Alcohol-Related Hepatocellular Carcinoma. A Microbial Culturomics Study. 2025; Preprint (Version 1) available at Research Square DOI: https://doi.org/10.21203/rs.3.rs-5053117/v1

21. Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A. The Genus Alistipes: Gut Bacteria with Emerging Implications to Inflammation, Cancer, and Mental Health. Front Immunol. 2020;11:906. DOI: https://doi.org/10.3389/fimmu.2020.00906

22. Zhuang J, Zhuang Z, Chen B, Yang Y, Chen H, Guan G. Odoribacter splanchnicus-derived extracellular vesicles alleviate inflammatory bowel disease by modulating gastrointestinal inflammation and intestinal barrier function via the NLRP3 inflammasome suppression. Mol Med. 2025;31(1):56. DOI: https://doi.org/10.1186/s10020-025-01063-2

23. Beresford-Jones BS, Suyama S, Clare S, Soderholm A, Xia W, Sardar P, et al. Enterocloster clostridioformis protects against Salmonella pathogenesis and modulates epithelial and mucosal immune function. Microbiome. 2025;13(1):61. DOI: https://doi.org/10.1186/s40168-025-02050-9