ISSN 2226-6976 (Print)
ISSN 2414-9640 (Online)

Genotype-associated changes in the composition of intestinal microbiota in patients with chronic hepatitis C: an age-and-sex-adjusted analysis

Stoma I.O., Tseyko Z.A., Kovalev A.A., Voropaev E.V., Osipkina O.V., Zyatkov A.A., Shaforost A.S.

Gomel State Medical University, Gomel, Republic of Belarus
Objective. Comparative analysis the composition of the intestinal microbiota in patients with chronic HCV infection, infected with genotypes 1 and 3, taking into account age- and sex-adjusted characteristics.
Materials and methods. A single-center, cross-sectional clinical study including 119 patients with chronic hepatitis C was conducted. Gut microbial diversity was determined using 16S rRNA metagenomic sequencing. 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. Data were analyzed using Kraken2.
Results. In patients with HCV genotype 1, an increase in the number of such taxa as Helicobacter (padj < 0.001), Shewanella (padj = 0.101), Terribacillus (padj < 0.001), Providencia (padj = 0.050), Coprobacter (padj < 0.001), Duodenibacillus (padj = 0.044), Paraclostridium (padj = 0.008), Monoglobus (padj < 0.001), etc. was noted. And in patients with HCV genotype 3 - Yersinia (padj = 0.003), Citrobacter (padj = 0.010), Brevibacterium (padj = 0.001), Latilactobacillus (padj < 0.001), Butyrivibrio (padj = 0.085), Bombilactobacillus (padj < 0.001), etc.
Conclusion. Infection with HCV genotype 1 was associated with a metabolic imbalance with an increase in the abundance of opportunistic microorganisms, sulfate-reducing bacteria (Nitratidesulfovibrio (padj = 0.014), and bacteria involved in bile acid metabolism (Gordonibacter (padj = 0.112)). Patients with genotype 3 exhibit a mixed picture: an increase in the abundance of potential pathogens and a maintained presence of beneficial bacteria.

Keywords

chronic hepatitis C
intestinal microbiota
HCV genotype
microbiome
metagenomic sequencing

References

1. Liu Z., Shi O., Zhang T., Li J., Xingdong C. Disease burden of viral hepatitis A, B, C and E: A systematic analysis. J. Viral Hepat. 2020; 27(12): 1284–1296. DOI: 10.1111/jvh.13371

2. Morozov V.A., Lagaye S. Hepatitis C virus: Morphogenesis, infection and therapy. World J. Hepatol. 2018; 10(2): 186–212. DOI: 10.4254/wjh.v10.i2.186

3. Zhang L., Zi L., Kuang T., Wang K., Qiu Z., Wu Z. et al. Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study. Front. Endocrinol. (Lausanne) 2023; 14: 1159148. DOI: 10.3389/fendo.2023.1159148

4. Rodríguez J.M., Murphy K., Stanton C., Ross R.P., Kober O.I., Juge N. et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb. Ecol. Health Dis. 2015; 26: 26050. DOI: 10.3402/mehd.v26.26050

5. Стома И.О., Цейко З.А., Воропаев Е.В., Осипкина О.В., Ковалев А.А., Зятьков А.А. и др. Изменения кишечной микробиоты на фоне хронической HCV-инфекции в зависимости от генотипа вируса. Проблемы здоровья и экологии 2025; 22(2): 147–160. (Stoma I.O., Tseiko Z.A., Voropaev E.V., Osipkina O.V., Kovalev A.A., Ziatskov A.A. et al. Changes in the intestinal microbiota with a background of chronic HCV infection,depending on the genotype of the virus. Health and Ecology Issue 2025; 22(2): 147–160. (In Russ.)). DOI 10.51523/2708-6011.2025-22-2-18

6. Papamichael K., Konstantopoulos P., Mantzaris G.J. Helicobacter pylori infection and inflammatory bowel disease: is there a link? World J. Gastroenterol. 2014; 20(21): 6374–6385. DOI: 10.3748/wjg.v20.i21.6374

7. Wie S.H. Clinical significance of Providencia bacteremia or bacteriuria. Korean J. Intern. Med. 2015; 30(2): 167–169. DOI: 10.3904/kjim.2015.30.2.167

8. Henry E.A, Devereux R., Maki J.S., Gilmour C.C., Woese C.R., Mandelco L. et al. Characterization of a new thermophilic sulfate-reducing bacterium Thermodesulfovibrio yellowstonii, gen. nov. and sp. nov.: its phylogenetic relationship to Thermodesulfobacterium commune and their origins deep within the bacterial domain. Arch. Microbiol. 1994; 161(1): 63–69.

9. Campbell C., McKenney P.T., Konstantinovsky D., Isaeva O.I., Schizas M., Verter J. et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T-cells. Nature 2020; 581(7809): 475–479. DOI: 10.1038/s41586-020-2193-0.

10. Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl. Environ. Microbiol. 2008; 74(16): 4985–4996. DOI: 10.1128/AEM.00753-081

11. Loomba R., Seguritan V., Li W., Long T., Klitgord N., Bhatt A. et al. Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017; 2;25(5): 1054–1062.e5. DOI: 10.1016/j.cmet.2017.04.001

12. Singh V., Lee G., Son H., Koh H., Kim E.S., Unno T. et al. Butyrate producers, «The Sentinel of Gut»: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics. Front. Microbiol. 2023; 13: 1103836. DOI: 10.3389/fmicb.2022.1103836

13. Schneider R., Munk M., Lebuhnv B. Importance of Defluviitalea raffinosedens for Hydrolytic Biomass Degradation in Co-Culture with Hungateiclostridium thermocellum. Microorganisms 2020; 8(6): 915. DOI: 10.3390/microorganisms8060915

14. Lee N.Y., Suk K.T., The Role of the Gut Microbiome in Liver Cirrhosis Treatment. Int. J. Mol. Sci. 2021; 22(1): 199. DOI: 10.3390/ijms22010199

About the Authors

Professor Igor O. Stoma, MD, Rector, Gomel State Medical University, Gomel, Republic of Belarus; gsmu@gsmu.by; https://orcid.org/0000-0003-0483-7329
Zinaida A. Tseiko, Departmental Assistant, Department of Infectious Diseases, Gomel State Medical University, Gomel, Republic of Belarus; tzeiko.zinaida@yandex.by https://orcid.org/0000-0002-0610-1422
Evgenii V. Voropaev, Cand. Med. Sci., Associate Professor, Vice President for Research, Gomel State Medical University, Gomel, Republic of Belarus; voropaev.evgenii@gmail.com; https://orcid.org/0000-0002-9435-6109
Alexey A. Kovalev, Senior Lecturer, Department of Medical and Biological Physics, Gomel State Medical University, Gomel, Republic of Belarus; kovalev.data.analysis.gsmu@yandex.by; https://orcid.org/0000-0001-9148-487X
Olga V. Osipkina, Head, Research Laboratory, Gomel State Medical University, Gomel, Republic of Belarus; olga.osipkina@mail.ru; https://orcid.org/0000-0002-1931-4224
Aliaksey A. Ziatskov, Senior Researcher, Research Laboratory, Gomel State Medical University, Gomel, Republic of Belarus;ziatskovaa@gmail.com; https://orcid.org/0000-0001-9542-3791
Alexander S. Shaforost, Senior Researcher, Research Laboratory, Gomel State Medical University, Gomel, Republic of Belarus; asofocl@mail.ru; https://orcid.org/0000-0002-6725-5353

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