Gut microbiota and systemic inflammation in patients with chronic heart failure
https://doi.org/10.18087/cardio.2020.5.n859
Abstract
Aim To study the interrelationship between intensity of chronic systemic inflammation (CSI) with severity of the condition and intestinal microbiocenosis parameters in patients with chronic heart failure (CHF).
Material and methods 47 hospitalized patients with symptomatic CHF were evaluated. The following parameters were determined: clinical condition; N-terminal pro-B-type natriuretic peptide (NT-proBNP). C-reactive protein (CRP); serum interleukins (IL) 6 and 10; and intestinal microbiocenosis composition by mass-spectrometry of microbial markers in whole blood. Microbiocenosis indexes were compared in the main group and in 38 outpatient patients with arterial hypertension and ischemic heart disease without CHF.
Results Direct, medium-power correlations were found between CRP and IL-6 concentrations and severity of clinical condition (NT-proBNP, ХСН stage, and edema severity) in patients with CHF. Most patients with CHF had lower numbers of bifido-, lacto-, propionic-, and eubacteria, and Clostridium (С.) ramosum and higher numbers of aspergillus. Among CHF patients, the highest indexes of endotoxemia, gram (-) bacteria, cocci, actinomycetes, and microfungi were observed in the group with NT-proBNP from 400 to 2000 pg/ml. Direct correlations were observed for amounts of C. hystolyticum, Pseudonocardia spp., and Aspergillus spp. with IL-6 and IL-10 and unidirectional inverse correlation were observed for these cytokines with Propionibacterium acnes and jensenii, Streptomyces spp., and Nocardia asteroides. In addition, IL-6 concentration was negatively correlated with contents of Staphylococcus aureus, C. difficile, C. ramosum, Eggerthella lenta, and Corynebacterium spp. and was positively correlated with C. propionicum, Moraxella spp. and Flavobacterium spp. Concentration of IL-6 directly correlated with the number of Eubacterium spp. and inversely correlated with numbers of Ruminicoccus spp. and Streptomyces farmamarensis. The amount of Streptomyces farmamarensis negatively correlated with CRP concentrations.
Conclusion The study results evidence the significance of intestinal microbial-tissue complex in the pathogenesis of CSI in CHF and allow suggesting this complex as a promising target for therapy.
About the Authors
A. A. VlasovRussian Federation
candidate of medical Sciences, senior researcher, 2801-1228
S. P. Salikova
Russian Federation
doctor of medical Sciences, associate Professor 2nd Department (Medical Postgraduate Therapy), 2012-8481
V. B. Grinevich
Russian Federation
doctor of medical Sciences, Professor, head of 2nd Department (Medical Postgraduate Therapy), 1178-0242
O. V. Bystrova
Russian Federation
candidate of chemical Sciences, senior researcher, 5123-4769
G. A. Osipov
Russian Federation
doctor of biological Sciences, Professor, leading researcher
M. E. Meshkova
Russian Federation
candidate of biological Sciences, lecturer of clinical biochemistry and laboratory diagnostics, 6465-3776
References
1. Cihakova D. Interleukin-10 stiffens the heart. Journal of Experimental Medicine. 2018;215(2):379–81. DOI: 10.1084/jem.20180049
2. Ptaszynska-Kopczynska K, Szpakowicz A, Marcinkiewicz-Siemion M, Lisowska A, Waszkiewicz E, Witkowski M et al. Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy. Archives of Medical Science. 2017;13(5):1069–77. DOI: 10.5114/aoms.2016.58635
3. Lovett DH, Mahimkar R, Raffai RL, Cape L, Zhu B-Q, Jin Z-Q et al. N-Terminal Truncated Intracellular Matrix Metalloproteinase-2 Induces Cardiomyocyte Hypertrophy, Inflammation and Systolic Heart Failure. PLoS ONE. 2013;8(7):e68154. DOI: 10.1371/journal.pone.0068154
4. Egorova E.N., Mazur V.V., Kalinkin M.N., Mazur E.S. Role of endotoxin and systemic inflammation in chronic heart failure pathogenesis. Russian Journal of Cardiology. 2012;17(3):25–7.
5. Li X, Sun Y, Zhang X, Wang J. Reductions in gut microbiota‑derived metabolite trimethylamine N‑oxide in the circulation may ameliorate myocardial infarction‑induced heart failure in rats, possibly by inhibiting interleukin‑8 secretion. Molecular Medicine Reports. 2019;20(1):779–86. DOI: 10.3892/mmr.2019.10297
6. Ebner N, Földes G, Schomburg L, Renko K, Springer J, Jankowska EA et al. Lipopolysaccharide responsiveness is an independent predictor of death in patients with chronic heart failure. Journal of Molecular and Cellular Cardiology. 2015;87:48–53. DOI: 10.1016/j.yjmcc.2015.07.029
7. Arutyunov G.P., Kafarskaya L.I., Bylova N.A., Chernyavskaya T.K., Pokrovsky Yu.A., Korsunskaya M.I. et al. Qualitative and quantitative parameters of large intestinal microflora in different functional classes of chronic heart failure. Russian Heart Failure Journal. 2005;4(5):176– 80.
8. Pasini E, Aquilani R, Testa C, Baiardi P, Angioletti S, Boschi F et al. Pathogenic Gut Flora in Patients With Chronic Heart Failure. JACC: Heart Failure. 2016;4(3):220–7. DOI: 10.1016/j.jchf.2015.10.009
9. Zhou X, Li J, Guo J, Geng B, Ji W, Zhao Q et al. Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction. Microbiome. 2018;6(1):66. DOI: 10.1186/s40168-018-0441-4
10. Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S et al. Altered Intestinal Function in Patients With Chronic Heart Failure. Journal of the American College of Cardiology. 2007;50(16):1561–9. DOI: 10.1016/j.jacc.2007.07.016
11. Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H 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
12. Osipov G.A., Boyko N.B., Novikova V.P., Grinevich V.B., Fedosova N.F., Tsekh O.M. et al. Method of mass spectrometry of microbial markers as a way to assess the wall-to-wall intestinal microbiota in diseases of the digestive system. -SPb.: Levsha;2013. - 96 p.
13. Gheorghiade M, Follath F, Ponikowski P, Barsuk JH, Blair JEA, Cleland JG et al. Assessing and grading congestion in acute heart failure: a scientific statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. European Journal of Heart Failure. 2010;12(5):423–33. DOI: 10.1093/eurjhf/hfq045
14. Kurbanov R.D., Kurbanov N.A., Abdullaev T.A., Tsoy I.A., Akhmatov Ya.R. Morpho-functional parameters of the heart and features of immunity shifts in patients with chronic heart failure induced by dilated cardiomyopathy. Russian Heart Failure Journal. 2014;15(2):76–82.
15. Khamitova K.A., Chepurnaya A.N., Nikulicheva V.I., Safuanova G.Sh. Content of cytokine inflammatory markers in patients with chronic heart failure caused by cardiomyopathy. Acta Biomedica Scientifica. 2017;2(3):48–54.
16. Wang J-H, Zhao L, Pan X, Chen N-N, Chen J, Gong Q-L et al. Hypoxia- stimulated cardiac fibroblast production of IL-6 promotes myocardial fibrosis via the TGF-β1 signaling pathway. Laboratory Investigation. 2016;96(8):839–52. DOI: 10.1038/labinvest.2016.65
17. Podoprigora G.I., Kafarskaya L.I., Baynov N.A., Shkoporov A.N. Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects. Annals of the Russian academy of medical sciences. 2015;70(6):640–50. DOI: 10.15690/vramn564
18. Cui X, Ye L, Li J, Jin L, Wang W, Li S et al. Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients. Scientific Reports. 2018;8(1):635. DOI: 10.1038/s41598-017-18756-2
19. Kubyshkina N.A., Gaivoronskaya V.V., Apchel V.Ya. Endotoxin-induced alterations of functional activity of lymphatic vessels. Bulletin of the Russian Military Medical Academy. 2014;3(47):155–9.
20. Lobov G.I., Pankova M.N. Atrial Natriuretic Peptide Inhibits Spontaneous Contractile Activity of Lymph Nodes. Bulletin of Experimental Biology and Medicine. 2016;161(2):177–80.
21. Betge S, Stingl M, Pfister W, Figulla H-R, Jung C. Investigation of Bacterial Translocation in Chronic Ischemic Heart Failure in the Rat. Clinical Laboratory. 2015;61(1–2):93–100. DOI: 10.7754/Clin.Lab.2014.140719
22. Pinilla-Vera M, Xiong Z, Zhao Y, Zhao J, Donahoe MP, Barge S et al. Full Spectrum of LPS Activation in Alveolar Macrophages of Healthy Volunteers by Whole Transcriptomic Profiling. PLOS ONE. 2016;11(7):e0159329. DOI: 10.1371/journal.pone.0159329
23. Conaway EA, de Oliveira DC, McInnis CM, Snapper SB, Horwitz BH. Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation. The Journal of Immunology. 2017;198(7):2906–15. DOI: 10.4049/jimmunol.1601781
24. Wang F, Liu J, Weng T, Shen K, Chen Z, Yu Y et al. The Inflammation Induced by Lipopolysaccharide can be Mitigated by Short-chain Fatty Acid, Butyrate, through Upregulation of IL-10 in Septic Shock. Scandinavian Journal of Immunology. 2017;85(4):258–63. DOI: 10.1111/sji.12515
25. Larsen JM, Musavian HS, Butt TM, Ingvorsen C, Thysen AH, Brix S. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology. Immunology. 2015;144(2):333–42. DOI: 10.1111/imm.12376
26. Bylova N.A., Kafarskaya L.I., Chernaya Z.A. Role of Cl. dificile in development of systemic inflammation in frequently hospitalized patients with CHF. Russian Heart Failure Journal. 2011;12(1):31–5.
27. Tuovinen E, Keto J, Nikkilä J, Mättö J, Lähteenmäki K. Cytokine response of human mononuclear cells induced by intestinal Clostridium species. Anaerobe. 2013;19:70–6. DOI: 10.1016/j.anaerobe.2012.11.002
28. Elikowski W, Małek-Elikowska M, Lisiecka M, Mozer-Lisewska I. Fatal course of takotsubo cardiomyopathy in a female with recurrent Clostridium difficile infection. Polski Merkuriusz Lekarski. 2017;42(252):256–9. PMID: 28662012
29. Sato T, Watanabe K, Kumada H, Toyama T, Tani-Ishii N, Hamada N. Peptidoglycan of Actinomyces naeslundii induces inflammatory cytokine production and stimulates osteoclastogenesis in alveolar bone resorption. Archives of Oral Biology. 2012;57(11):1522–8. DOI: 10.1016/j.archoralbio.2012.07.012
30. Punsmann S, Liebers V, Stubel H, Brüning T, Raulf-Heimsoth M. Determination of inflammatory responses to Aspergillus versicolor and endotoxin with human cryo-preserved blood as a suitable tool. International Journal of Hygiene and Environmental Health. 2013;216(4):402–7. DOI: 10.1016/j.ijheh.2012.11.001
31. Sawamura A, Okumura T, Hiraiwa H, Aoki S, Kondo T, Ichii T et al. Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy. Journal of Cardiology. 2017;69(6):888–94. DOI: 10.1016/j.jjcc.2016.08.012
32. Rabah H, Rosa do Carmo F, Jan G. Dairy Propionibacteria: Versatile Probiotics. Microorganisms. 2017;5(2):24. DOI: 10.3390/microorganisms5020024
33. Ali A, Khajuria A, Sidiq T, Kumar A, Thakur NL, Naik D et al. Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene from the marine derived Streptomyces sp. Immunology Letters. 2013;150(1–2):79–86. DOI: 10.1016/j.imlet.2012.09.001
Review
For citations:
Vlasov A.A., Salikova S.P., Grinevich V.B., Bystrova O.V., Osipov G.A., Meshkova M.E. Gut microbiota and systemic inflammation in patients with chronic heart failure. Kardiologiia. 2020;60(5):74–82. https://doi.org/10.18087/cardio.2020.5.n859