Comparative analysis of the composition of intestinal microbiome in patients with liver diseases

Authors

DOI:

https://doi.org/10.15587/2519-8025.2020.192721

Keywords:

intestinal dysbiosis, nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C

Abstract

Aim: to analyze the composition of the intestinal microbiome in patients with liver diseases of various etiologies.

Materials and methods: 128 patients of different sexes with pathological liver lesions were examined. The diagnosis of diseases was carried out using laboratory and instrumental methods of research. The study of the composition of microbiota in qualitative and quantitative indicators was carried out using standard bacteriological methods. The statistical analysis was performed using Student's t-test. Differences in indicators were considered significant at P<0.05.

Results: the comparative analysis of the composition of the intestinal microbiocenosis of patients with various liver diseases showed significant drops in the titers of symbiotic bacteria: lactobacilli to 100–104 CFU/ml, bifidobacteria to 105–108 CFU/ml, enterococci to 105–106 CFU/ml and typical E. coli to 103–106 CFU/ml, as well as an increase in the number of opportunistic microorganisms: Candida to 104–109 CFU/ml, hemolytic E. coli to 107–109 CFU/ml, Staphylococcus spp. to 104–106 CFU/ml, Klebsiella spp. and Enterobacter spp. to 106–108 CFU/ml. According to the degree of colonization of associative and conditionally pathogenic microbiota of the intestinal tract, significant fluctuations in the deviations of indicators were recorded in women and men with non-alcoholic steatohepatitis, alcoholic hepatitis and hepatitis C.

Conclusions: the study revealed the significant imbalance of microbiome of the gastrointestinal tract: there was a tendency to increase the quantitative and qualitative indicators of the content of representatives of the opportunistic microbiota against the background of decreasing titers of symbiotic microorganisms. The most significant deviations in the composition of the intestinal microbiome were observed in patients with hepatitis C. The differences in the microbial landscape of the intestine of patients of different sex with liver diseases are shown, which was mentioned in the changing relationship of individual members of the intestinal microbiota

Author Biographies

Vladyslav Martynov, Oles Honchar Dnipro National University Gagarina ave., 72, Dnipro, Ukraine, 49010

Department of Microbiology, Virology and Biotechnology

Viktoriia Havryliuk, Oles Honchar Dnipro National University Gagarina ave., 72, Dnipro, Ukraine, 49010

PhD, Associate Professor

Department of Microbiology, Virology and Biotechnology

Tetiana Skliar, Oles Honchar Dnipro National University Gagarina ave., 72, Dnipro, Ukraine, 49010

PhD, Associate Professor

Department of Microbiology, Virology and Biotechnology

Iryna Sokolova, Oles Honchar Dnipro National University Gagarina ave., 72, Dnipro, Ukraine, 49010

PhD, Associate Professor

Department of Microbiology, Virology and Biotechnology

References

  1. Compare, D., Coccoli, P., Rocco, A., Nardone, O. M., De Maria, S., Cartenì, M., Nardone, G. (2012). Gut–liver axis: The impact of gut microbiota on non alcoholic fatty liver disease. Nutrition, Metabolism and Cardiovascular Diseases, 22 (6), 471–476. doi: http://doi.org/10.1016/j.numecd.2012.02.007
  2. Trukhan, D. I., Viktorova, I. A., Safonov, A. D. (2019). Bolezni pecheni. Saint-Peterburg, 239.
  3. Loomba, R., Sanyal, A. J. (2013). The global NAFLD epidemic. Nature Reviews Gastroenterology & Hepatology, 10 (11), 686–690. doi: http://doi.org/10.1038/nrgastro.2013.171
  4. Aron-Wisnewsky, J., Gaborit, B., Dutour, A., Clement, K. (2013). Gut microbiota and non-alcoholic fatty liver disease: new insights. Clinical Microbiology and Infection, 19 (4), 338–348. doi: http://doi.org/
  5. Gangarapu, V., Yildiz, K., Tuzun Ince, A., Baysal, B. (2014). Role of gut microbiota: Obesity and NAFLD. The Turkish Journal of Gastroenterology, 25 (2), 133–140. doi: http://doi.org/
  6. Miele, L., Valenza, V., La Torre, G., Montalto, M., Cammarota, G., Ricci, R. et. al. (2009). Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology, 49 (6), 1877–1887. doi: http://doi.org/10.1002/hep.22848
  7. Zhu, L., Baker, S. S., Gill, C., Liu, W., Alkhouri, R., Baker, R. D., Gill, S. R. (2013). Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH. Hepatology, 57 (2), 601–609. doi: http://doi.org/10.1002/hep.26093
  8. Lieber, C. S. (1993). Aetiology and pathogenesis of alcoholic liver disease. Baillière’s Clinical Gastroenterology, 7 (3), 581–608. doi: http://doi.org/10.1016/0950-3528(93)90003-b
  9. Hartmann, P., Seebauer, C. T., Schnabl, B. (2015). Alcoholic Liver Disease: The Gut Microbiome and Liver Cross Talk. Alcoholism: Clinical and Experimental Research, 39 (5), 763–775. doi: http://doi.org/10.1111/acer.12704
  10. Aly, A. M., Adel, A., El-Gendy, A. O., Essam, T. M., & Aziz, R. K. (2016). Gut microbiome alterations in patients with stage 4 hepatitis C. Gut Pathogens, 8 (1). doi: http://doi.org/10.1186/s13099-016-0124-2
  11. EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. (2016). Journal of Hepatology, 64 (6), 1388–1402. doi: http://doi.org/10.1016/j.jhep.2015.11.004
  12. EASL Clinical Practical Guidelines: Management of Alcoholic Liver Disease (2012). Journal of Hepatology, 57 (2), 399–420. doi: http://doi.org/10.1016/j.jhep.2012.04.004
  13. Brenner, D. J., Krieg, N. R., Staley, J. T. (Eds.). (2005). Bergey’s Manual of Systematic Bacteriology. Boston: Springer. doi: http://doi.org/10.1007/0-387-29298-5
  14. Backhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A. et. al. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences, 101 (44), 15718–15723. doi: http://doi.org/10.1073/pnas.0407076101
  15. Drenick, E. J., Fisler, J., Johnson, D. (1982). Hepatic Steatosis After Intestinal Bypass—Prevention and Reversal by Metronidazole, Irrespective of Protein-Calorie Malnutrition. Gastroenterology, 82 (3), 535–548. doi: http://doi.org/10.1016/s0016-5085(82)80403-4
  16. Cope, K., Risby, T., Diehl, A. M. (2000). Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis. Gastroenterology, 119 (5), 1340–1347. doi: http://doi.org/10.1053/gast.2000.19267
  17. Baker, S. S., Baker, R. D., Liu, W., Nowak, N. J., Zhu, L. (2010). Role of Alcohol Metabolism in Non-Alcoholic Steatohepatitis. PLoS ONE, 5 (3), e9570. doi: http://doi.org/10.1371/journal.pone.0009570
  18. Lichtman, S. N., Keku, J., Schwab, J. H., Sartor, R. B. (1991). Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology, 100 (2), 513–519. doi: http://doi.org/10.1016/0016-5085(91)90224-9
  19. Yokota, A., Fukiya, S., Islam, K. B. M. S., Ooka, T., Ogura, Y., Hayashi, T. et. al. (2012). Is bile acid a determinant of the gut microbiota on a high-fat diet? Gut Microbes, 3 (5), 455–459. doi: http://doi.org/10.4161/gmic.21216
  20. Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A. et. al. (2012). Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature, 487 (7405), 104–108. doi: http://doi.org/10.1038/nature11225
  21. Turnbaugh, P. J. (2012). Fat, bile and gut microbes. Nature, 487 (7405), 47–48. doi: http://doi.org/10.1038/487047a
  22. Machado, M. V., Cortez-Pinto, H. (2012). Gut microbiota and nonalcoholic fatty liver disease. Annals of Hepatology, 11 (4), 440–449. doi: http://doi.org/10.1016/s1665-2681(19)31457-7
  23. Tremaroli, V., Bäckhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature, 489 (7415), 242–249. doi: http://doi.org/10.1038/nature11552
  24. Abu-Shanab, A., Quigley, E. M. M. (2010). The role of the gut microbiota in nonalcoholic fatty liver disease. Nature Reviews Gastroenterology & Hepatology, 7 (12), 691–701. doi: http://doi.org/10.1038/nrgastro.2010.172
  25. Casafont Morencos, F., de Las Heras Castaño, G., Martín Ramos, L., López Arias, M. J., Ledesma, F., Pons Romero, F. (1996). Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Digestive Diseases and Sciences, 41 (3), 552–556. doi: http://doi.org/10.1007/bf02282340
  26. Mutlu, E., Keshavarzian, A., Engen, P., Forsyth, C. B., Sikaroodi, M., Gillevet, P. (2009). Intestinal Dysbiosis: A Possible Mechanism of Alcohol-Induced Endotoxemia and Alcoholic Steatohepatitis in Rats. Alcoholism: Clinical and Experimental Research, 3 3(10), 1836–1846. doi: http://doi.org/10.1111/j.1530-0277.2009.01022.x
  27. Canesso, M. C. C., Lacerda, N. L., Ferreira, C. M., Gonçalves, J. L., Almeida, D., Gamba, C. et. al. (2014). Comparing the effects of acute alcohol consumption in germ-free and conventional mice: the role of the gut microbiota. BMC Microbiology, 14 (1). doi: http://doi.org/10.1186/s12866-014-0240-4
  28. Bajaj, J. S., Heuman, D. M., Hylemon, P. B., Sanyal, A. J., White, M. B., Monteith, P. et. al. (2014). Altered profile of human gut microbiome is associated with cirrhosis and its complications. Journal of Hepatology, 60 (5), 940–947. doi: http://doi.org/10.1016/j.jhep.2013.12.019
  29. Leclercq, S., Matamoros, S., Cani, P. D., Neyrinck, A. M., Jamar, F., Stärkel, P. et. al. (2014). Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. Proceedings of the National Academy of Sciences, 111 (42), E4485–E4493. doi: http://doi.org/10.1073/pnas.1415174111
  30. Bajaj, J. S., Ridlon, J. M., Hylemon, P. B., Thacker, L. R., Heuman, D. M., Smith, S. et. al. (2012). Linkage of gut microbiome with cognition in hepatic encephalopathy. American Journal of Physiology-Gastrointestinal and Liver Physiology, 302 (1), G168–G175. doi: http://doi.org/10.1152/ajpgi.00190.2011
  31. Liu, Q., Duan, Z. P., Ha, D. K., Bengmark, S., Kurtovic, J., Riordan, S. M. (2004). Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology, 39 (5), 1441–1449. doi: http://doi.org/10.1002/hep.20194
  32. Gupta, A., Dhiman, R. K., Kumari, S., Rana, S., Agarwal, R., Duseja, A., Chawla, Y. (2010). Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy. Journal of Hepatology, 53 (5), 849–855. doi: http://doi.org/10.1016/j.jhep.2010.05.017
  33. Chari, S., Teyssen, S., Singer, M. V. (1993). Alcohol and gastric acid secretion in humans. Gut, 34 (6), 843–847. doi: http://doi.org/10.1136/gut.34.6.843
  34. Dinoso, V. P. (1972). Gastric secretion and gastric mucosal morphology in chronic alcoholics. Archives of Internal Medicine, 130 (5), 715–719. doi: http://doi.org/10.1001/archinte.130.5.715
  35. Shindo, K., Machida, M., Miyakawa, K., Fukumura, M. (1993) A syndrome of cirrhosis, achlorhydria, small intestinal bacterial overgrowth, and fat malabsorption. American Journal of Gastroenterology, 88, 2084–2091.
  36. Yan, A. W., E. Fouts, D., Brandl, J., Stärkel, P., Torralba, M., Schott, E. et. al. (2010). Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology, 53 (1), 96–105. doi: http://doi.org/10.1002/hep.24018
  37. Hartmann, P., Chen, P., Wang, H. J., Wang, L., McCole, D. F., Brandl, K. et. al. (2013). Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology, 58 (1), 108–119. doi: http://doi.org/10.1002/hep.26321
  38. Hetta, H. F. (2014). Gut immune response in the presence of hepatitis C virus infection. World Journal of Immunology, 4 (2), 52. doi: http://doi.org/10.5411/wji.v4.i2.52
  39. Mantis, N. J., Rol, N., Corthésy, B. (2011). Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunology, 4 (6), 603–611. doi: http://doi.org/10.1038/mi.2011.41
  40. Haro, C., Rangel-Zúñiga, O. A., Alcalá-Díaz, J. F., Gómez-Delgado, F., Pérez-Martínez, P., Delgado-Lista, J. et. al. (2016). Intestinal Microbiota Is Influenced by Gender and Body Mass Index. PLOS ONE, 11 (5), e0154090. doi: http://doi.org/10.1371/journal.pone.0154090

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Published

2020-04-30

How to Cite

Martynov, V., Havryliuk, V., Skliar, T., & Sokolova, I. (2020). Comparative analysis of the composition of intestinal microbiome in patients with liver diseases. ScienceRise: Biological Science, (2 (23), 15–22. https://doi.org/10.15587/2519-8025.2020.192721

Issue

No. 2 (23) (2020)

Section

Biological Sciences

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Copyright (c) 2020 Владислав Олександрович Мартинов, Вікторія Григорівна Гаврилюк, Тетяна Володимирівна Скляр, Ірина Євгенівна Соколова

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