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Intestinal Microbial-tissue Complex and Chronic Heart Failure (part 1): Pathogenesis

https://doi.org/10.20996/1819-6446-2021-06-12

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Abstract

Antigenic and metabolic integration of the intestinal microbiota into the homeostasis of the human body is a factor that claims to play a key role in the pathogenesis of cardiovascular diseases. It acquires special significance against the background of the decrease in blood circulation and congestion in the digestive system during chronic heart failure. Aim of the review is analysis and synthesis of studies results on the role of intestinal microbiocenosis in the pathogenesis of heart remodeling and chronic heart failure. The search for articles was conducted in databases eLIBRARY.RU and Medline for the key terms "gut microbiota (microbiome, microbiocenosis)", "dysbiosis (dysbacteriosis)", "excessive bacterial growth syndrome", "lipopolysaccharide (endotoxin)", "trimethylamine-N-oxide" in combination with the terms "heart failure", "myocardial remodeling", "myocardium" in Russian and English, respectively. We selected articles containing the results of clinical and experimental studies published from 1995 to 2020. Review articles were considered only on the subject of the cited original publications. Most researchers have established the relationship between chronic heart failure and dysfunction and changes in the qualitative and quantitative composition of intestinal microbiocenosis. As negative changes, it is customary to note the proliferation of gram-negative opportunistic bacteria with concomitant endotoxinemia and a decrease in the pool of commensal microbiota. The available data suggest that the participation of the intestinal microbial-tissue complex in the pathogenesis of chronic heart failure and heart remodeling is realized through the activation of a local and then systemic inflammatory response, accompanied by cardiodepressive action of pro-inflammatory cytokines and universal proliferation factors, an imbalance of matrix metalloproteinases and their inhibitors, the initiation of apoptosis, fibrosis, and loss of contractile myocardium. Besides, a decrease in the production of short-chain and polyunsaturated fatty acids and vitamins by the commensal microbiota may be associated with changes in the electrical properties of cardiomyocyte membranes, a decrease in the systolic function of the left ventricle of the heart, and an increase in the risk of sudden cardiac death. It's also shown that the direct cardiotoxic effect of microbial molecules (lipopolysaccharides, peptidoglycans, trimethylamine-N-oxide, etc.), which interact with the receptors of cardiomyocytes and microenvironment cells, can cause the development of myocardial remodeling and its dysfunction. Recent studies have established mechanisms of myocardial remodeling mediated by microbial molecules, which may be associated with new strategies for the treatment and prevention of heart failure.

About the Authors

A. A. Vlasov
33th Central research and testing Institute
Russian Federation

 

Andrey A. Vlasov - eLibrary SPIN 2801-1228

Volsk



S. P. Salikova
Military Medical Academy named after S.M. Kirov
Russian Federation

Svetlana P. Salikova - eLibrary SPIN 2012-8481

St. Petersburg



N. V. Golovkin
St. Petersburg City hospital of Saint George
Russian Federation

Nikita V. Golovkin

St. Petersburg



V. B. Grinevich
Military Medical Academy named after S.M. Kirov
Russian Federation

Vladimir B. Grinevich - eLibrary SPIN 1178-0242

St. Petersburg



References

1. Arutyunov GP, Kafarskaya LI, Bylova NA. Qualitative and quantitative indicators of the colon microflora in various functional classes of chronic heart failure. Russian Heart Failure Journal. 2005;5:176-80 (In Russ.)

2. Egorova EN, Kuzmina MI, Mazur VV, et al. Microbiocenosis and activity of the inflammatory process in the colon of the patients with chronic cardiac failure. Clinical Medicine. 2012;90(7):46-8. (In Russ.)

3. Niebauer J, Volk HD, Kemp M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999;353(9167):1838-42. DOI:10.1016/S0140-6736(98)09286-1.

4. Pasini E, Aquilani R, Testa C, et al. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016;4(3):220-7. DOI:10.1016/j.jchf.2015.10.009.

5. Ebner N, Földes G, Schomburg L, et al. Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure. J Mol Cell Cardiol. 2015;87:48-53. DOI:10.1016/j.yjmcc.2015.07.029.

6. Oliveira AJM, Farias LD, Mafra V, Cota J. The angiotensin converting enzyme 2 (ACE2), gut microbiota, and cardiovascular health. Protein Pept Lett. 2017;24(9):827-32. DOI:10.2174/0929866524666170728145333.

7. Grinevich VB, Sas EI, Efimov OI, Denisov NL. The role of gut microbial-tissue complex in development of chronic system inflammation and insulin-resistance in patients with non-alcoholic fatty liver disease. Bulletin of the St. Petersburg Medical Academy of Postgraduate Education. 2010;2(4):19-24 (In Russ.)

8. Polsinelli VB, Sinha A, Shah SJ. Visceral congestion in heart failure: right ventricular dysfunction, splanchnic hemodynamics, and the intestinal microenvironment. Curr Heart Fail Rep. 2017;14(6):519-28. DOI:10.1007/s11897-017-0370-8.

9. Tang WH. We are not alone: understanding the contributions of intestinal microbial communities and the congested gut in heart failure. JACC Heart Fail. 2016;4(3):228-9. DOI:10.1016/j.jchf.2015.12.004.

10. Arutyunov GP, Kafarskaya LI, Savelov NA, et al. Chronic heart failure: structural and microbiological changes in the colon. Ter Arkhiv. 2007;79(2):31-7 (In Russ.)

11. Arutyunov GP, Kostyukevich OI, Serov RA, et al. Morphofunctional changes in the small intestine in patients with chronic cardiac failure. Ter Arkhiv. 2004;76(2):40-4 (In Russ.)

12. Verbitskaya VS, Korpacheva OV, Khramykh TP. Dysfunction of small intestine mucosa in posttraumatic period of cardiac contusion. Polytrauma. 2011;3:84-8 (In Russ.)

13. Yue C, Ma B, Zhao Y, et al. Lipopolysaccharide-induced bacterial translocation is intestine sitespecific and associates with intestinal mucosal inflammation. Inflammation. 2012;35(6):1880-8. DOI:10.1007/s10753-012-9510-1.

14. Arutyunov GP, Kostyukevich OI, Rylova NV, et al. Collagen accumulation and dysfunctional mucosal barrier of the small intestine in patients with chronic heart failure. Intern J Cardiol. 2008;125(2):240-5. DOI:10.1016/j.ijcard.2007.11.103.

15. Falchuk EL, Markov AG. The study of barrier characteristics of peyer’s patches epithelium in rats. Vestnik of St. Petersburg University. Series 3. Biology. 2015;3:75-86 (In Russ.)

16. Anker SD, Egerer KR, Volk HD, et al. Elevated soluble CD14 receptors and altered cytokines in chronic heart failure. Am J Cardiol. 1997;79(10):1426-30. DOI:10.1016/s0002-9149(97)00159-8.

17. Hill DA, Artis D. Intestinal bacteria and the regulation of immune cell homeostasis. Annu Rev Immunol. 2010;28:623-67. DOI:10.1146/annurev-immunol-030409-101330.

18. Podoprigora GI, Kafarskaya LI, Bainov NA, Shkoporov AN. Bacterial Translocation from intestine: microbiological, immunological and pathophysiological aspects. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk. 2015;70(6):640-50 (In Russ.)

19. Betge S, Stingl M, Pfister W, et al. Investigation of bacterial translocation in chronic ischemic heart failure in the rat. Clin Lab. 2015;61(1-2):93-100. DOI:10.7754/clin.lab.2014.140719.

20. Zolotova NA, Akhrieva KhM, Zayratyants OV. Epithelial barrier of the colon in health and patients with ulcerative colitis. Experimental and Clinical Gastroenterology. 2019;162(2):4-13 (In Russ.) DOI:10.31146/1682-8658-ecg-162-2-4-13.

21. Ivashkin KV, Shirokova EN, Ivashkin VT, et al. Myocardial Contractile Function in Patients with Liver Cirrhosis and Syndrome of Bacterial Overgrowth Syndrome. Kardiologiia. 2019;59(4):67-73 (In Russ.) DOI:10.18087/cardio.2019.4.10252.

22. Krack A, Sharma R, Figulla HR, Anker SD. The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J. 2005;26(22):2368-74. DOI:10.1093/eurheartj/ehi389.

23. Sandek A, Swidsinski A, Schroedl W, et al. Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia. J Am Coll Cardiol. 2014;64(11):1092-102. DOI:10.1016/j.jacc.2014.06.1179.

24. Anikhovskaya IA, Salakhov IM, Yakovlev MYu. Intestinal endotoxin and stress adaptation and aging. Bulletin of RANS. 2016;1:19-24 (In Russ.)

25. Kubyshkina NA, Gaivoronskaya VV, Apchel VYa. Endotoxin-induced alterations of functional activity of lymphatic vessels. Bulletin of the Russian Military Medical ACADEMY. 2014;3(47):155-9 (In Russ.)

26. Pankova MN, Lobov GI. The inhibitory effect of IL-1β on the contractile activity of smooth muscle capsule lymph nodes. Regionarnoe Krovoobraŝenie i Mikrocirkulâciâ. 2013;12(3):53-6 (In Russ.)

27. Lobov GI, Pan’kova MN. Atrial Natriuretic Peptide Inhibits Spontaneous Contractile Activity of Lymph Nodes Bulletin of Experimental Biology and Medicine. 2016;161(2):221-3 (In Russ.)

28. Nalban N, Sangaraju R, Alavala S, et al. Arbutin Attenuates Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting TLR-4/NF-κB Pathway in Mice. Cardiovasc Toxicol. 2020;20(3):235-48. DOI:10.1007/s12012-019-09548-3.

29. Meng YY, Liu Y, Hu ZF, et al. Sanguinarine Attenuates Lipopolysaccharide-induced Inflammation and Apoptosis by Inhibiting the TLR4/NF-κB Pathway in H9c2 Cardiomyocytes. Curr Med Sci. 2018;38(2):204-11. DOI:10.1007/s11596-018-1867-4.

30. Magi S, Nasti AA, Gratteri S, et al. Gram-negative endotoxin lipopolysaccharide induces cardiac hypertrophy: detrimental role of Na(+)-Ca(2+) exchanger. Eur J Pharmacol. 2015;746:31-40. DOI:10.1016/j.ejphar.2014.10.054.

31. Liu M, Mao C, Li J, et al. Effects of the Activin A-Follistatin system on myocardial cell apoptosis through the endoplasmic reticulum stress pathway in heart failure. Int J Mol Sci. 2017;18(2):374. DOI:10.3390/ijms18020374.

32. Gnauck A, Lentle RG, Kruger MC. Chasing a ghost? - Issues with the determination of circulating levels of endotoxin in human blood. Crit Rev Clin Lab Sci. 2016;53(3):197-215. DOI:10.3109/10408363.2015.1123215.

33. Xu X, Hicks C, Li Y, et al. Purified cell wall from the probiotic bacterium Lactobacillus gasseri activates systemic inflammation and; at higher doses; produces lethality in a rat model. Crit Care. 2014;18(4):R140. DOI:10.1186/cc13966.

34. Barros J.P, Gautier T, Sali W, et al. Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay. J. Lipid. Res. 2015;56(7):1363-69. DOI:10.1194/jlr.D059725.

35. Panchenko LF, Moiseev VS, Pirozhkov SV, et al. Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure. Kardiologiia. 2015;3:41-8 (In Russ.)

36. Nordgren L, Sörensen S. Symptoms experienced in the last six months of life in patients with endstage heart failure. Eur. J. Cardiovasc. Nurs. 2003;2(3):213-17. DOI:10.1016/S1474-5151(03)00059-8.

37. Staller K, Khalili H, Kuo B. Constipation prophylaxis reduces length of stay in elderly hospitalized heart failure patients with home laxative use. J Gastroenterol Hepatol. 2015;30(11):1596-602. DOI:10.1111/jgh.13011.

38. Kalinkin MN, Osadchiy VA, Bukanova TYu. Clinical and morphological features of inflammatory and atrophic lesions of gastroduodenal zone in elderly patients with congestive heart failure associated with coronary artery disease and role of microcirculation, heamostasis and gastric secretion disorders in their development. Clinical Gerontology. 2015;21(3-4):18-23 (In Russ.)

39. Karpukhin OYu, Shakurov AF, Koporulina MO. Level of endotoxin as a criterion of severity of chronic constipation and efficiency of its treatment. Practical Medicine. 2014;5(81):58-61 (In Russ.)

40. Cui X, Ye L, Li J, et al. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Sci Rep. 2018;8(1):635. DOI:10.1038/s41598-017-18756-2.

41. Simbirtseva AS, Bylova NA, Arutyunov AG, et al. Prognostic role of body composition in patients with pneumonia associated with decompensated CHF. Kardiologiia. 2017;57(S2):343-50 (In Russ.) DOI:10.18087/cardio.2392.

42. Sandek A, Bauditz J, Swidsinski A, et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50(16):1561-9. DOI:10.1016/j.jacc.2007.07.016.

43. Sandek A, Bjarnason I, Volk HD, et al. Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure. Int J Cardiol. 2012;157(1):80-5. DOI:10.1016/j.ijcard.2010.12.016.

44. Schaufelberger M, Ekman I, Björnsson E, et al. Intestinal paracellular permeability is not affected in chronic congestive heart failure. Eur J Heart Fail. 2007;9(6-7):574-8. DOI:10.1016/j.ejheart.2007.02.005.

45. Zamolodchikova TS, Shoibonov BB, Tolpygo SM. Local rennin angiotensin system of small intestine. Eksperimentalnaya i Klinicheskaya Gastroenterologiya. 2015;124(12):97-104 (In Russ.)

46. Poleshchuk EO. Enhancing the effects of adrenaline on heart activity under the influence of intestinal endotoxin. News of Medical and Biological Sciences. 2010;2(3):46-50 (In Russ.)

47. Nagatomo Y, Tang WHW. Intersections between microbiome and heart failure: revisiting the gut hypothesis. J Card Fail. 2015;21(12):973-80. DOI:10.1016/j.cardfail.2015.09.017.

48. Kamo T, Akazawa H, Suda W, et al. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS One. 2017;12(3):e0174099. DOI:10.1371/journal.pone.0174099.

49. Osipov GA, Novikova VP, eds. Method of mass spectrometry of microbial markers as a method for assessing the parietal intestinal microbiota in diseases of the diges-tive system: Teaching-methodical manual. Saint Petersburg: Levsha; 2013 (In Russ.)

50. Marsinkevich EV, Gavrilenya AD. Effect of probiotics on the colon microflora of rats in chronic heart failure. Problems of Health and Ecology. 2013;3(37):114-17 (In Russ.)

51. Bykova NA, Kafarskaya LI, Chernaya ZA. Role of Cl. dificile in development of systemic inflammation in frequently hospitalized patients with CHF. Journal of heart failure. 2011;12(1):31-5. (In Russ.)

52. Mamic P, Heidenreich PA, Hedlin H, et al. Hospitalized patients with heart failure and common bacterial infections: a nationwide analysis of concomitant Clostridium difficile infection rates and inhospital mortality. J Card Fail. 2016;22(11):891-900. DOI:10.1016/j.cardfail.2016.06.005.

53. Tuovinen, E, Keto J, Nikkilä J, et al. Cytokine response of human mononuclear cells induced by intestinal Clostridium species. Anaerobe. 2013;19:70-6. DOI:10.1016/j.anaerobe.2012.11.002.

54. Elikowski W, Małek-Elikowska M, Lisiecka M, Mozer-Lisewska I. Fatal course of takotsubo cardiomyopathy in a female with recurrent Clostridium difficile infection. Pol Merkur Lekar. 2017;42(252):56-9.

55. Henke MT, Kenny DJ, Cassilly CD, et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proceedings of the National Academy of Sciences. 2019;116(26):12672-7. DOI:10.1073/pnas.1904099116.

56. Ivashkin VT, Kashukh YA. Impact of L-carnitine and phosphatidylcholine containing products on the proatherogenic metabolite TMAO production and gut microbiome changes in patients with coronary artery disease. Voprosy Pitaniya. 2019;88(4):25-33 (In Russ.) DOI:10.24411/0042-8833-2019-10038.

57. Zhou X, Jin M, Liu L, et al. Trimethylamine-N-oxide and cardiovascular outcomes in patients with chronic heart failure after myocardial infarction. ESC Heart Fail. 2020;7(1):188-93. DOI:10.1002/ehf2.12552.

58. Hayashi T, Yamashita T, Watanabe H, et al. Gut Microbiome and Plasma Microbiome-Related Metabolites in Patients With Decompensated and Compensated Heart Failure. Circ J. 2018;83(1):182-92. DOI:10.1253/circj.CJ-18-0468.

59. Hoyles L, Jiménez-Pranteda ML, Chilloux J, et al. Metabolic retroconversion of trimethylamine-Noxide and the gut microbiota. Microbiome. 2018;6(1):73. DOI:10.1186/s40168-018-0461-0.

60. Kashukh EA, Poluektova EA, Kudryavtseva AV, et al. Effect of Rifaximin and a Multi-Strain Probiotic on the Intestinal Microbiome and Cardiovascular Risk Indicators in Patients with Coronary Heart Disease. The Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(4):38-49 (In Russ.) DOI:10.22416/1382-4376-2019-29-4-38-49.

61. Yang W, Zhang S, Zhu J, et al. Gut microbe-derived metabolite trimethylamine N-oxide accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis. J Mol Cell Cardiol. 2019;134:119-30. DOI:10.1016/j.yjmcc.2019.07.004.

62. Li Z, Wu Z, Yan J et al. Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis. Lab Invest. 2019;99(3):346-57. DOI:10.1038/s41374-018-0091-y.

63. Nurgeldyeva MD, Khodjakuli BG. Features of atherogenesis at sensitivity increase to Candida albicans. Eurasian Heart Journal. 2013;1:70-5. (In Russ.)

64. Martsynkevich E.V., Soltanov V.V. Effect of administration of probiotics on the morphological and functional status of heart and colon of the rats. Vesti of the National Academy of Sciences of Belarus. Medical Science Series. 2016;2:23-9 (In Russ.)

65. Sawamura A, Okumura T, Hiraiwa H, et al. Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy. J Cardiol. 2017;69(6):888-94. DOI:10.1016/j.jjcc.2016.08.012.

66. Zaglieva SS, Mammaev SN, Zagliev SG. Interconnection cytokines and infectious factors in patients with chronic heart failure due to coronary heart disease. Bulletin of the Dagestan State Medical Academy. 2013;1(6):28-33 (In Russ.)

67. Kruchinkina EV, Ryabova TR, Rogovskaya YuV, et al. The incidence and profile of cardiotropic viral antigens in the myocardium in patients with decompensated chronic heart failure with systolic dysfunction of ischemic origin. The Siberian Medical Journal. 2017;32(1):46-9 (In Russ.)

68. Carding SR, Davis N, Hoyles L. Review article: the human intestinal virome in health and disease. Aliment Pharmacol Ther. 2017;46(9):800-15. DOI:10.1111/apt.14280.

69. Wang F, Liu J, Weng T, et al. The inflammation induced by lipopolysaccharide can be mitigated by short-chain fatty acid, butyrate, through upregulation of IL-10 in septic shock. Scand J Immunol. 2017;4:258-63. DOI:10.1111/sji.12515.

70. Wang C, Xiong B, Huang J. The Role of Omega3 Polyunsaturated Fatty Acids in Heart Failure: A MetaAnalysis of Randomised Controlled Trials. Nutrients. 2016;9(1):E18. DOI:10.3390/nu9010018.

71. Hennessy AA, Barrett E, Ross RP, et al. The production of conjugated α-linolenic, γ-linolenic and stearidonic acids by strains of bifidobacteria and propionibacteria. Lipids. 2012;47(3):313-27. DOI:10.1007/s11745-011-3636-z.

72. Wall R, Ross RP, Shanahan F, et al. Impact of administered bifidobacterium on murine host fatty acid composition. Lipids. 2010;45:429-36. DOI:10.1007/s11745-010-3410-7.

73. Patterson E, O'Doherty RM, Murphy EF, et al. Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice. Br J Nutr. 2014;111(11):1905-17. DOI:10.1017/S0007114514000117.


For citation:


Vlasov A.A., Salikova S.P., Golovkin N.V., Grinevich V.B. Intestinal Microbial-tissue Complex and Chronic Heart Failure (part 1): Pathogenesis. Rational Pharmacotherapy in Cardiology. 2021;17(3):462-469. (In Russ.) https://doi.org/10.20996/1819-6446-2021-06-12

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