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https://doi.org/10.14300/mnnc.2021.16052

Metabolic integration of the «gut – liver»: theoretical basis of interaction and therapeutic prospects

[Reviews]
Alina Alekseevna Shevandova; Irina Ivanovna Fomochkina; Anatoly Vladimirovich Kubyshkin; Leya Evgenievna Sorokina; Andrey Ivanovich Gordienko; Aleksandr Andreevich Gorbunov; Tatiana Pavlovna Makalish; Ksenia Andreevna Yurchenko;

Recently, the role of intestinal microbiota in maintaining metabolic and immunological homeostasis has received increasing attention. Many studies have reported a close association between intestinal ecosystem dysbiosis and the development of several pathological processes, including autoimmune, metabolic, and malignant diseases. Because there is a steady increase in the numbers of patients with liver diseases, future studies of the function of the gut-liver axis will be important. The relationship between the liver and intestines occurs through bidirectional signal exchange via metabolic, epigenetic, and neuroendocrine mechanisms. The quantitative and qualitative characteristics of the intestinal microflora can affect intestinal permeability and the translocation of endotoxins, as well as control the activity of Kupffer cells and the transcriptional activation of many proinflammatory genes and cytokines in the liver through the production of various metabolites. The normalization of intestinal microflora might be a promising method for the treatment and prevention of socially significant liver diseases.

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References:
1. Turnbaugh P. J., Ley R. E., Hamady M., Fraserliggett C. M., Knight R. [et al.] The human microbiome project. Nature. 2007;449(7164):804-10. https://doi.org/10.1038/nature06244
2. O’Hara A. M., Shanahan F. The gut flora as a forgotten organ. EMBO. 2006;7:688-693. https://doi.org/10.1038/sj.embor.7400731
3. Marchesi J. R., Ravel J. The vocabulary of microbiome research: a proposal. Microbiome. 2015;3:31-35. https://doi.org/10.1186/s40168-015-0094-5
4. Zoetendal E. G., Rajilic-Stojanovic M., de Vos W. M. High through put diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008;57:1605-1615. https://doi.org/10.1136/gut.2007.133603
5. Arora T., Bäckhed F. The gut microbiota and metabolic disease: current understanding and future perspectives. Journal of Internal Medicine. 2016;280(4):339-349. https://doi.org/10.1111/joim.12508
6. Cresci G. A., Bawden E. Gut Microbiome: What We Do and Don’t Know. Nutrition in Clinical Practice. 2015;30(6):734-46. https://doi.org/10.1177/0884533615609899
7. Poluektova E. A., Ljashenko O. S., Shifrin O. S., Sheptulin A. A., Ivashkin V. T. Modern methods for studying the microflora of the human gastrointestinal tract. Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii. – Russian journal of Gastroenterology, Hepatology, Coloproctology. 2014;24(2):85-91.
8. Landman C., Qmvrain E. Gut microbiota: Description, role and pathophysiologic implications. La Revue de Médecine Interne. 2016;37(6):418-423. https://doi.org/10.1016/j.revmed.2015.12.012
9. Shi N., Li N., Duan X., Niu H. Interaction between the gut microbiome and mucosal immune system. Military Medical Research. 2017;4:14. https://doi.org/10.1186/s40779-017-0122-9
10. Guarner F., Malagelada J. R. Gut flora in health and disease. Lancet. 2003;361(9356):512-519. https://doi.org/10.1016/S0140-6736(03)12489-0
11. Boulangè C. L., Neves A. L., Chilloux J. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Medicine. 2016;68:42-63. https://doi.org/10.1186/s13073-016-0303-2
12. Maynard C., Weinkove D. The Gut Microbiota and Ageing. Sub-cellular biochemistry. 2018;90:351-371. https://doi.org/10.1007/978-981-13-2835-0_12
13. Milosevic I., Vujovic A., Barac A., Djelic M., Korac M. [et al.] Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. International journal of molecular sciences. 2019;20(2):395. https://doi.org/10.3390/ijms20020395
14. Federico A., Dallio M., Caprio G. G., Ormando V. M., Loguercio C. Gut microbiota and the liver. Minerva Gastroenterologica e Dietologica. 2017;63(4):385-398. https://doi.org/10.23736/S1121-421X.17.02375-3
15. Seki E., Schnabl B. Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut. The Journal of Physiology. 2012;590(3):447-458. https://doi.org/10.1113/jphysiol.2011.219691
16. Seo Y. S., Shab V. H. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension. Clinical and Molecular Hepatology. 2012;18(4):337-346. https://doi.org/10.3350/cmh.2012.18.4.337
17. Boursier J., Mueller O., Barret M., Machado M., Fizanne L. [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. 2016;63(3):764-75. https://doi.org/10.1002/hep.28356
18. Bajaj J. S., Heuman D. M., Hylemon P. B., Fisher A. R., Sikaroodi M. [et al.] Altered profile of human gut microbiome is associated with cirrhosis and its complications. Journal of Hepatology. 2014;60:940-7. https://doi.org/10.1016/j.jhep.2013.12.019
19. Delzenne N. M., Knudsen C., Beaumont M., Rodriguez J., Neyrinck A. M. [et al.] Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut-liver axis. The Proceedings of the Nutrition Society. 2019;78(3):319-328. https://doi.org/10.1017/S0029665118002756
20. Michail S., Lin M., Frey M. R., Fanter R., Paliy O. [et al.] Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease. FEMS Microbiology Ecology. 2015;91(2):1-9. https://doi.org/10.1093/femsec/fiu002
21. Raman M., Ahmed I., Gillevet P. M. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology. 2013;11(7):868-75. https://doi.org/10.1016/j.cgh.2013.02.015
22. Grat M., Wronka K. M., Krasnodębski M. Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis. Transplantation Proceedings. 2016;48:1687-1691. https://doi.org/10.1016/j.transproceed.2016.01.077
23. Xie G., Wang X., Zhao A. Sex-dependent effects on gut microbiota regulate hepatic carcinogenic outcomes. Scientific Reports. 2017;7:45232. https://doi.org/10.1038/srep45232
24. Schoeler M., Caesar R. Dietary lipids, gut microbiota and lipid metabolism. Reviews in Endocrine & Metabolic Disorders. 2019;20(4):461-472. https://doi.org/10.1007/s11154-019-09512-0
25. Paul B., Barnes S., Demark-Wahnefried W. Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases. Clinical Epigenetics. 2015;7:112-129. https://doi.org/10.1186/s13148-015-0144-7
26. Thaiss C. A., Zmora N., Levy M., Elinav E. The microbiome and innate immunity. Nature. 2016;535(7610):65-74. https://doi.org/10.1038/nature18847
27. Carbajo-Pescador S., Porras D., García-Mediavilla M. V., Martínez-Flórez S., Juarez-Fernández M. [et al.] Beneficial effects of exercise on gut microbiota functionality and barrier integrity, and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease. Disease models & mechanisms. 2019;12(5):dmm039206. https://doi.org/10.1242/dmm.039206
28. Xu R., Aruhan, Xiu L., Sheng S., Liang Y., Zhang H. [et al.] Exopolysaccharides from Lactobacillus buchneri TCP016 Attenuate LPS- and d-GalN-Induced Liver Injury by Modulating the Gut Microbiota. Journal of agricultural and food chemistry. 2019;67(42):11627-11637. https://doi.org/10.1021/acs.jafc.9b04323
29. Li R., Zhou R., Wang H., Li W., Pan M. [et al.] Gut microbiota-stimulated cathepsin K secretion mediates TLR4-dependent M2 macrophage polarization and promotes tumor metastasis in colorectal cancer. Cell Death & Differentiation. 2019;26(11):2447-2463. https://doi.org/10.1038/s41418-019-0312-y
30. Liu D., Zhang Y., Liu Y., Hou L., Li S. [et al.] Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway. Experimental and Clinical Endocrinology & Diabetes. 2018;126(8):513-520. https://doi.org/10.1055/s-0043-125066
31. Law K., Brunt E. M. Nonalcoholic fatty liver disease. Clinics in Liver Disease. 2010;14(4):591-604. https://doi.org/10.1016/j.cld.2010.07.006
32. Park E. J., Lee J. H., Yu G. Y. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010;140:197-208. https://doi.org/10.1016/j.cell.2009.12.052
33. Szabo G., Lippai D. Molecular hepatic carcinogenesis: impact of inflammation. Digestive Diseases. 2012;30(3):243-8. https://doi.org/10.1159/000336913
34. Shiffka S. J., Kane M. A., Swaan P. W. Planar bile acids in health and disease. Biochimica et Biophysica Acta. Biomembranes. 2017;1859(11):2269-2276. https://doi.org/10.1016/j.bbamem.2017.08.019
35. Dawson Р. A., Karpen S. J. Intestinal transport and metabolism of bile acids. Journal of Lipid Research. 2015;56(6):1085-99. https://doi.org/10.1194/jlr.R054114
36. Ridlon J. M., Harris S. C., Bhowmik S., Kang D. J., Hylemon P. B. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes. 2016;7(1):22-39. https://doi.org/10.1080/19490976.2015.1127483
37. McGlone E. R., Bloom S. R. Bile acids and the metabolic syndrome. Annals of clinical biochemistry. 2019;56(3):326-337. https://doi.org/10.1177/0004563218817798
38. Jung D., Podvinec M., Meyer U. A., Mangelsdorf D. J., Fried M. [et al.] Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology. 2002;122(7):1954-66. https://doi.org/10.1053/gast.2002.33583
39. Norlin M., Andersson U., Björkhem I., Wikvall K. Oxysterol 7 alpha-hydroxylase activity by cholesterol 7 alpha-hydroxylase (CYP7A). The Journal of biological chemistry. 2000;275(44):34046-53. https://doi.org/10.1074/jbc.M002663200
40. Russell D. W. The enzymes, regulation, and genetics of bile acid synthesis. Annual Review of Biochemistry. 2003;72(1):137-74. https://doi.org/10.1146/annurev.biochem.72.121801.161712
41. Bai X., Dong F., Yang G. Influences of sterol regulatory element binding protein-1c silencing on glucose production in HepG2 cells treated with free fatty acid. Lipids in Health and Disease. 2019;18:89. https://doi.org/10.1186/s12944-019-1026-3
42. Ji Y., Yin Y., Li Z., Zhang W. Gut Microbiota-Derived Components and Metabolites in the Progression of Non-Alcoholic Fatty Liver Disease. Nutrients. 2019;11(8):1712. https://doi.org/10.3390/nu11081712
43. Suk K. T., Kim D. J. 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
44. Keitel V., Görg B., Bidmon H. J., Zemtsova I., Spomer L. [et al.] The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain. Glia. 2010;58(15):1794-805. https://doi.org/10.1002/glia.21049
45. Keitel V., Häussinger D. Role of TGR5 (GPBAR1) in Liver Disease. Seminars in Liver Disease. 2018;38(4):333-339. https://doi.org/10.1055/s-0038-1669940
46. Alemi F., Poole D. P., Chiu J., Schoonjans K., Cattaruzza F. [et al.] The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology. 2013;144(1):145-54. https://doi.org/10.1053/j.gastro.2012.09.055
47. Deutschmann K., Reich M., Klindt C., Dröge C., Spomer L. [et al.] Bile acid receptors in the biliary tree: TGR5 in physiology and disease. Biochimica et Biophysica Acta. Molecular Basis of Disease. 2018;1864:1319-1325. https://doi.org/10.1016/j.bbadis.2017.08.021
48. Ma C., Han M., Heinrich B., Fu Q., Zhang Q. [et al.] Gut microbiome – mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 2018;360(6391):5931. https://doi.org/10.1126/science.aan5931
49. Geissmann F., Cameron T. O., Sidobre S., Manlongat N., Kronenberg M. [et al.] Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biology. 2005;3(4):113. https://doi.org/10.1371/journal.pbio.0030113

Keywords: intestinal microbiota, intestinal microflora, gut-liver metabolic axis, non-alcoholic fatty liver disease, irrhosis, hepatocellular carcinoma