Pathogenetic relationship between the condition gut microbiota and liver diseases

Abstract

The human commensal microbiota is a collection of all microorganisms (viruses, bacteria, fungi) inhabiting different places of the human body. The composition of species, the ratio of potentially pathogenic strains and representatives of the normal human microbiota affect the predisposition to diseases, the nature of their course. Its role in the pathogenesis of malignant neoplasms, autism, depression, Clostridium difficile infection, autoimmune, endocrine and other diseases has been proven. There is increasing evidence of the impact of the microbiota on the course of liver disease, including viral hepatitis. It is noted that changes in the gut microbiota composition and an increase of intestinal barrier permeability are observed even at the initial stages of the disease, before the development of significant liver fibrosis and cirrhosis. This literature review presents the results of studies of the microbiota in patients with liver cirrhosis, viral hepatitis B and C, its effect on metabolism and immune responses that determine the nature of the course of the pathological process in the liver.

Keywords:microbiota; microbiome; metabolome; viral hepatitis B; viral hepatitis C; liver cirrhosis

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

Contribution. The authors contributed equally to this article.

For citation: Ventslovayte N.D., Goriacheva L.G., Gonchar N.V., Greshnyakova V.A., Efremova N.A. Pathogenetic relationship between the condition gut microbiota and liver diseases. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2022; 11 (2): 97–105. DOI: https://doi.org/10.33029/2305-3496-2022-11-2-97-105

References

1. Leung D.H., Yimlamai D. The intestinal microbiome and paediatric liver disease. Lancet Gastroenterol Hepatol. 2017; 2 (6): 446–55.

2. Booijink C.C., Zoetendal E.G., Kleerebezem M., de Vos W.M. Microbial communities in the human small intestine: coupling diversity to metagenomics. Future Microbiol. 2007; 2: 285–95.

3. Zoetendal E.G., Rajilic-Stojanovic M., de Vos W.M. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008; 57: 1605–15.

4. Kim C.H. Immune regulation by microbiome metabolites. Immunology. 2018; 154 (2): 220–9.

5. Kim M., Kim C.H. Regulation of humoral immunity by gut microbial products. Gut Microbes. 2017; 8: 392–9.

6. Kasubuchi M., Hasegawa S., Hiramatsu T., Ichimura A., Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015; 7: 2839–49.

7. Seliverstov P.V., Sitkin S.I., Radchenko V.G., Lazebnik L.B., Avalueva E.B., Vakhitov T.Ya., et al. Saccharomyces boulardii modulates the composition of the gut microbiota in patients with non-alcoholic fatty liver disease, thus preventing the progression of the disease. Exp Clin Gastroenterol. 2018; 150 (2): 4–18.

8. Sung M. C., Lin Y. F., Chen K. F., et al. Predicting clinical outcomes of cirrhosis patients with hepatic encephalopathy from the fecal microbiome. Cell Mol Immunol. 2019; 8 (2): 301.e2–18.e2.

9. Wang Y., Pan C.Q., Xing H. Advances in gut microbiota of viral hepatitis cirrhosis. Biomed Res Int. 2019; 2019: 9726786.

10. Shah A., Shanahan E., Macdonald G., et al. Systematic review and meta-analysis: prevalence of small intestinal bacterial overgrowth in chronic liver disease. Semin Liver Dis. 2017; 37 (4): 388–400.

11. Kakiyama G., Pandak W.M., Hylemon P.B., et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J Hepatol. 2013; 58 (5): 949–55.

12. Lin R., Zhou L., Zhang J., Wang B. Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis. Int J Clin Exp Pathol. 2015; 8 (5): 5153–60.

13. Cai W., Ran Y., Li Y., Wang B., Zhou L. Intestinal microbiome and permeability in patients with autoimmune hepatitis. Best Pract Res Clin Gastroenterol. 2017; 31 (6): 669–73.

14. Kang Y., Cai Y. Gut microbiota and hepatitis-B-virus-induced chronic liver disease implications for faecal microbiota transplantation therapy. J Hosp Infect. 2017; 96 (4): 342–8.

15. Paik Y.H., Schwabe R.F., Bataller R., Russo M.P., Jobin C., Brenner D.A. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology. 2003; 37 (5): 1043–55.

16. Seki E., De Minicis S., Osterreicher C.H., Kluwe J., Osawa Y., Brenner D.A., et al TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 2007; 13: 1324–32.

17. Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell. 2010; 140: 805–20.

18. Bauer S., Kirschning C.J., Häcker H., Redecke V., Hausmann S., Akira S., et al. Human TLR-9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA. 2001; 98: 9237–42.

19. Wahlström A., Sayin S. I., Marschall H.-U., Bäckhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016; 24 (1): 41–50.

20. Duboc H., Tache Y., Hofmann A.F. The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis. 2014; 46: 302–12.

21. Sayin S.I., Wahlström A., Felin J., Jäntti S., Marschall H.U., Bamberg K., et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-betamuricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013; 17: 225–35.

22. Neuschwander-Tetri B.A., Loomba R., et al.; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015; 385: 956–65.

23. Zhao Z.H., Xin F.Z., Xue Y., et al. Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats. Exp Mol Med. 2019; 51 (9): 1–14. Epub 2019 Sep 10. DOI: https://doi.org/10.1038/s12276-019-0304-5

24. Zhao Z.H., Xin F.Z., Xue Y.Q., et al. Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats. Exp Mol Med. 2019; 51 (9): 1–14. DOI: https://doi.org/10.1038/s12276-019-0304-5

25. Leung C., Rivera L., Furness J.B., Angus P.W. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol. 2016; 13 (7): 412–25. DOI: https://doi.org/10.1038/nrgastro.2016.85

26. Vital M., Howe A.C., Tiedje J.M. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. mBio. 2014; 5 (2): e00889. DOI: https://doi.org/10.1128/mBio.00889-14

27. Zhang J., Song L., Wang Y., Liu C., Zhang L., Zhu S., et al. Beneficial effect of butyrate-producing Lachnospiraceae on stress-induced visceral hypersensitivity in rats. J Gastroenterol Hepatol. 2019; 34: 1368–76. DOI: https://doi.org/10.1111/jgh.14536

28. Zeng H., Li L., Hou Z., Zhang Y., Tang Z., Liu S. Direct-acting antiviral in the treatment of chronic hepatitis c: bonuses and challenges. Int J Med Sci. 2020; 17 (7): 892–902.

29. Pecoraro V., Banzi R., Cariani E., Chester J., Villa E., D’Amico R., et al. New direct-acting antivirals for the treatment of patients with hepatitis C Virus infection: a systematic review of randomized controlled trials. J Clin Exp Hepatol. 2019; 9 (4): 522–38.

30. Curry M.P., O‘Leary J.G., Bzowej N., Muir A.J., Korenblat K.M., Fenkel J.M., et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med. 2015; 373: 2618–28.

31. Kozbial K., Moser S., Al-Zoairy R., Schwarzer R., Datz C., Stauber R., et al. Follow-up of sustained virological responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment. Liver Int. 2018; 38: 1028–35.

32. Aly A.M., Adel A., El-Gendy A.O., Essam T.M., Aziz R.K. Gut microbiome alterations in patients with stage 4 hepatitis C. Gut Pathog. 2016; 8 (1): 42.

33. Munteanu D., Negru A., Radulescu M., et al. Evaluation of bacterial translocation in patients with chronic HCV infection. Rom J Intern Med. 2014; 52: 91–6.

34. Bajaj J.S., Sterling R.K., Betrapally N.S., Nixon D.E., Fuchs M., Daita K., et al. HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients. Aliment Pharmacol Ther. 2016; 44 (6): 638–43. Epub 2016 Jul 15. DOI: https://doi.org/10.1111/apt.13732 PMID: 27417456.

35. Preveden T., Scarpellini E., Milić N., Luzza F., Abenavoli L. Gut microbiota changes and chronic hepatitis C virus infection. Expert Rev Gastroenterol Hepatol. 2017; 11 (9): 813–9.

36. Qin N., Yang F., Li A., et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014; 513: 59–64.

37. Albhaisi S.A., Sanyal A.J. The role of the gut microbiota in liver disease. Am J Physiol Gastrointest Liver Physiol. 2020; 318: G84–98.

38. Gómez-Hurtado I., Such J., Francés R. Microbiome and bacterial translocation in cirrhosis. Gastroenterol Hepatol. 2016; 39: 687–96.

39. Fukui H. Gut microbiota and host reaction in liver diseases. Microorganisms. 2015; 3: 759–91. DOI: https://doi.org/10.3390/microorganisms3040759

40. Ren Z., Li A., Jiang J., et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut. 2019; 68 (6): 1014–23. DOI: https://doi.org/10.1136/gutjnl-2017-315084

41. Wang J., Wang Y., Zhang X., et al. Gut microbial dysbiosis is associated with altered hepatic functions and serum metabolites in chronic hepatitis B patients. Front Microbiol. 2017; 8: 2222. DOI: https://doi.org/10.3389/fmicb.2017.02222

42. Wei X., Yan X., Zou D., Yang Z., Wang X., Liu W., et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach. BMC Gastroenterol. 2013; 13: 175.

43. Chen Y., Yang F., Lu H., Wang B., Chen Y., Lei D., et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011; 54: 562–72.

44. Bajaj J. S., Heuman D. M., Hylemon P. B., et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014; 60 (5): 940–7.

45. Ponziani F.R., Putignani L., Paroni Sterbini F., Petito V., Picca A., Del Chierico F., et al. Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis. Aliment Pharmacol Ther. 2018; 48 (11–12): 1301–11. DOI: https://doi.org/10.1111/apt.15004

46. Heidrich B., Vital M., Plumeier I., Doscher N., Kahl S., Kirschner J., et al. Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls. Liver Int. 2018; 38: 50–8.

47. Furusawa Y., Obata Y., Fukuda S., et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013; 504: 446–8.

48. Milosevic I., Vujovic A., Barac A., Djelic M., Korac M., Radovanovic Spurnic A., et al. Gut-liver axis, gut microbiota, and its modulation in the management of liver diseases: a review of the literature. Int J Mol Sci. 2019; 20 (2): 395.

49. Inoue T., Nakayama J., Moriya K., Kawaratani H., Momoda R., Ito K., et al. Gut dysbiosis associated with hepatitis C virus infection. Clin Infect Dis. 2018; 67 (6): 869–77.

50. Sultan S., El-Mowafy M., Elgaml A., El-Mesery M., El Shabrawi A., Elegezy M., et al. Alterations of the treatment-naive gut microbiome in newly diagnosed hepatitis c virus infection. ACS Infect Dis. 2021; 7 (5): 1059–68.

51. Bajaj J.S., Sterling R.K., Betrapally N.S., Nixon D.E., Fuchs M., Daita K., et al. HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients. Aliment Pharmacol Ther. 2016; 44 (6): 638–43. Epub 2016 Jul 15. DOI: https://doi.org/10.1111/apt.13732 PMID: 27417456.

52. Pérez-Matute P., Íñiguez M., Villanueva-Millán M.J., Recio-Fernández E., Vázquez A.M., Sánchez S.C., et al. Short-term effects of direct-acting antiviral agents on inflammation and gut microbiota in hepatitis C-infected patients. Eur J Intern Med. 2019; 67: 47–58. DOI: https://doi.org/10.1016/j.ejim.2019.06.005

53. D‘Ambrosio R., Aghemo A., Rumi M.G., et al. A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis. Hepatology. 2012; 56: 532–43.

54. Liang T.J. Hepatitis B: The virus and disease. Hepatology. 2009; 49 (5): S13–21.

55. Chou H.H. Chien W.H., Wu L.L., et al. Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota. Proc Natl Acad Sci USA. 2015; 112 (7): 2175–80.

56. Xu D., Huang Y., Wang J. Gut microbiota modulate the immune effect against hepatitis B virus infection. Eur J Clin Microbiol Infect Dis. 2015; 34 (11): 2139–47.

57. Seki E., Schnabl B. Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut. J Physiol. 2012; 590: 447–58.

58. Bermudez-Brito M., Muñoz-Quezada S., Gomez-Llorente C., et al. Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases pro-inflammatory cytokines in human dendritic cells challenged with Salmonella typhi through TLR activation. PLoS One. 2013; 8 (3): e59370.

59. Kang Y., Cai Y. Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy. J Hosp Infect. 2017; 96 (4): 342–8.

60. Lu H., Wu Z., Xu W., Yang J., Chen Y., Li L. Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients. Microb Ecol. 2011; 61 (3): 693–703.

61. Ling Z., Liu X., Cheng Y., et al. Decreased diversity of the oral microbiota of patients with hepatitis B virus-induced chronic liver disease: a pilot project. Sci Rep. 2015; 5: 17098.

62. Yang R., Xu Y., Dai Z., Lin X., Wang H. The immunologic role of gut microbiota in patients with chronic HBV infection. J Immunol Res. 2018; 2018: 2361963.

63. Wei X., Yan X., Zou D., Yang Z., Wang X., Liu W., et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach. BMC Gastroenterol. 2013; 13: 175.

64. Ren Y.D., Ye Z.S., Yang L.Z., et al. Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy. Hepatology. 2017; 65 (5): 1765–8.

65. Solov’eva O.I., Simanenkov V.I., Suvorov A.N., Ermolenko E.I., Shumihina I.A., Svirido D.A. The use of probiotics and autoprobiotics in the treatment of irritable bowel syndrome. Eksperimental’naya i klinicheskaya gastoenterologiya [Experimental and Clinical Gastroenterology]. 2017; 7 (143): 115–20. (in Russian)

CHIEF EDITOR
CHIEF EDITOR
Yushchuk Nikolay Dmitrievich
Academician of the Russian Academy of Sciences, Professor, head of the Infectious Diseases and Epidemiology Department, President of the Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Board member of the National Scientific Infectiologists? Society.
Вскрытие
Medicine today

II Всероссийская конференция с международным участием "Воспаление глаза" 12 ноября 2022 года, Москва Воспалительные заболевания глаза - широко распространенная и многогранная проблема, с которой может столкнуться в своей практике любой специалист. Найти оптимальные алгоритмы...

Масштабное событие в области дерматовенерологии и косметологии - II конференция InteDeCo 2022 "Интегративная дерматовенерология и косметология. Новые стандарты взаимодействия" - состоится 16-17 декабря 2022 года. Программа мероприятия пройдет на современной...

VIII Московский Городской Съезд педиатров с межрегиональным и международным участием "Трудный диагноз в педиатрии" Приглашаем педиатров, детских эндокринологов, реаниматологов, гинекологов, неонатологов, кардиологов, хирургов, урологов, психологов, специалистов по лучевой...


Journals of «GEOTAR-Media»