Mikrobiol. Z. 2022; 84(3):51-59.
doi: https://doi.org/10.15407/microbiolj84.03.051

Dependence of Intestinal Microbiota Composition on Distribution and Activity
of Adipose Tissue in Nonalcoholic Fatty Liver Disease

G.D. Fadieienko, I.E. Kushnir, V.M. Chernova, T.A. Solomentseva, Ya.V. Nikiforova,
O.H. Kurinna, V.Yu. Galchynska, T.N. Bondar

Malaya National Institute of Therapy, NAMS of Ukraine
2а Liubovi Maloi Ave., Kharkiv, 61039, Ukraine

Nonalcoholic fatty liver disease (NAFLD) pathogenesis displays a close relation with intestinal dysbiosis. Thus, the aim of this study was to investigate the intestinal microbiota (IM) composition and to determine the correlation of changes in its main phylotypes with the amount and activity of adipose tissue in NAFLD patients. Methods. The prospective study enrolled 114 NAFLD patients with metabolic disorders and 30 healthy subjects as the control group. Along with routine examination, the authors assessed intestinal microbiota composition by identifying total bacterial DNA and DNA of Bacteroidetes, Firmicutes, and Actinobacteria by means of a quantitative real-time PCR. Results. NAFLD patients showed a signifi cant decrease in the relative amount of Bacteroidetes with a simultaneous increase in the Firmicutes and an increase in Firmicutes/Bacteroidetes ratio compared with healthy subjects (p<0.05). NAFLD patients with concomitant overweight and obesity displayed a more significant imbalance of IM with an increase in the Firmicutes/Bacteroidetes ratio due to the inhibition of Bacteroidetes, compared with patients of normal body mass index. The revealed changes in the main phylotypes of IM in the examined patients were proven linked not only to an increase in body weight but also to the amount and activity of visceral adipose tissue. Furthermore, deviations in the gut microbiota composition had an impact on the formation and severity of steatosis. Conclusions. The study revealed an imbalance of IM in NAFLD patients. Further research in gut microbiota will help to elucidate their role in NAFLD pathogenesis and to lay a foundation for the development of individualized treatment.

Keywords: Nonalcoholic fatty liver disease, Bacteroidetes, Firmicutes, Actinobacteria.

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  1. Llorente C, Schnabl B. The gut microbiota and liver disease. Cellular and molecular gastroenterology and hepatology. 2015; 1(3):275—84. https://doi.org/10.1016/j.jcmgh.2015.04.003
  2. Ma J, Zhou Q, Li H. Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and Th erapy. Nutrients. 2017; 9(10). https://doi.org/10.3390/nu9101124
  3. He J, Yang XF. Gut microbiota and nonalcoholic fatty liver disease. World Chin J Dig. 2017; 25:5. https://doi.org/10.11569/wcjd.v25.i27.2480
  4. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World journal of gastroenterology. 2015; 21(29):8787—803. https://doi.org/10.3748/wjg.v21.i29.8787
  5. Macpherson AJ, de Agüero MG, Ganal-Vonarburg SC. How nutrition and the maternal microbiota shape the neonatal immune system. Nature reviews Immunology. 2017; 17(8):508—17. https://doi.org/10.1038/nri.2017.58
  6. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, et al. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms. 2019; 7(1). https://doi.org/10.3390/microorganisms7010014
  7. Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014; 146(6):1449—58. https://doi.org/10.1053/j.gastro.2014.01.052
  8. Suk KT, Kim DJ. Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease. Expert review of gastroenterology & hepatology. 2019; 13(3):193—204. https://doi.org/10.1080/17474124.2019.1569513
  9. Brandl K, Kumar V, Eckmann L. Gut-liver axis at the frontier of host-microbial interactions. American journal of physiology Gastrointestinal and liver physiology. 2017; 312(5):G413—G9. https://doi.org/10.1152/ajpgi.00361.2016
  10. Quesada-Vázquez S, Aragonès G, Del Bas JM, Escoté X. Diet, Gut Microbiota and Non-Alcoholic Fatty Liver Disease: Th ree Parts of the Same Axis. Cells. 2020; 9(1). https://doi.org/10.3390/cells9010176
  11. Schroeder BO, Bäckhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nature medicine. 2016; 22(10):1079—89. https://doi.org/10.1038/nm.4185
  12. Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology (Baltimore, Md). 2013; 58(1):120—7. https://doi.org/10.1002/hep.26319
  13. Zhang C, Zhang M, Pang X, Zhao Y, Wang L, Zhao L. Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. The ISME journal. 2012; 6(10):1848—57. https://doi.org/10.1038/ismej.2012.27
  14. Amato MC, Giordano C, Galia M, Criscimanna A, Vitabile S, Midiri M, et al. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes care. 2010; 33(4):920—2. https://doi.org/10.2337/dc09-1825
  15. Bacchetti De Gregoris T, Aldred N, Clare AS, Burgess JG. Improvement of phylum- and class-specifi c primers for real-time PCR quantification of bacterial taxa. Journal of microbiological methods. 2011; 86(3):351—6. https://doi.org/10.1016/j.mimet.2011.06.010
  16. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. Jama. 2015; 313(22):2263—73. https://doi.org/10.1001/jama.2015.5370
  17. Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, et al. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clinical gastroenterology and hepatology: the official clinical practice. Journal of the American Gastroenterological Association. 2013; 11(7):868—75.e1—3. https://doi.org/10.1016/j.cgh.2013.02.015
  18. Zmora N, Zeevi D, Korem T, Segal E, Elinav E. Taking it Personally: Personalized Utilization of the Human Microbiome in Health and Disease. Cell host & microbe. 2016; 19(1):12—20. https://doi.org/10.1016/j.chom.2015.12.016
  19. Suárez M, Boqué N, Del Bas JM, Mayneris-Perxachs J, Arola L, Caimari A. Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease. Nutrients. 2017; 9(10). https://doi.org/10.3390/nu9101052
  20. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006; 444(7122):1022—3. https://doi.org/10.1038/4441022a
  21. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012; 486(7402):222—7. https://doi.org/10.1038/nature11053
  22. Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology (Baltimore, Md). 2016; 63(3):764—75. https://doi.org/10.1002/hep.28356
  23. Guohong L, Qingxi Z, Hongyun W. Characteristics of intestinal bacteria with fatty liver diseases and cirrhosis. Annals of hepatology. 2019; 18(6):796—803. https://doi.org/10.1016/j.aohep.2019.06.020
  24. Wieland A, Frank DN, Harnke B, Bambha K. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Alimentary pharmacology & therapeutics. 2015; 42(9):1051–63. https://doi.org/10.1111/apt.13376