Intestinal dysbiosis in heart failure - modulation of dysbiosis as a potential therapeutic target
DOI:
https://doi.org/10.12775/JEHS.2023.44.01.014Keywords
heart failure, gut microbiota, biomarkers of heart failure, intestinal dysbiosisAbstract
The last decade has provided extensive information on the human gut microbiota. The microorganisms populating the gastrointestinal tract play important roles in maintaining the body's homeostasis. It turns out that the intestinal microbiota can affect many diseases from various branches of medicine. The importance of the function of the microflora can also affect cardiovascular diseases (CVD), including heart failure (HF). The microflora influences among other things, nutrient digestion, vitamin production or the production of bioactive metabolites including trimethylamine/trimethylamine N-oxide, short-chain fatty acids and bile acids. Therefore, changes in the composition of the intestinal microflora, defined as dysbiosis, have become one of the key pathogenic factors in many diseases. There is emerging evidence of a strong correlation between gut microflora and the occurrence of cardiovascular disease. In patients with cardiovascular disease and corresponding risk factors, the composition and proportions of the intestinal microflora differed significantly from healthy subjects.
Differences in microbial composition and marked fluctuations in the levels of biomarkers such as TMAO, zonulin, LPS, SCFAs may become helpful in the diagnosis of cardiovascular diseases. For this reason, the intestinal microflora and its metabolic pathways have recently become the subject of numerous studies. A very important issue is the fact that it is possible to regulate the intestinal microflora through diet, the use of prebiotics, probiotics or influence through a much larger intervention - for example, fecal mass transplantation. These possibilities have become new strategies in the treatment of HF. The main purpose of this review is to summarize recent studies that illustrate the complex interactions between the microbiome and the occurrence of HF.
Conclusions. The gut microbiota is a complex ecosystem of microorganisms that live in the human gut. The gut microbiota plays an important role in maintaining the body's health, including the cardiovascular system. Dysbiosis, or an imbalance in the gut microbiota, has been linked to the development of heart failure. Gut microbiota metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids, can have harmful effects on the heart. Diet, probiotics, and fecal microbiota transplantation (FMT) are all potential interventions for improving gut microbiota and reducing the risk of heart failure. More research is needed to fully understand the role of gut microbiota in heart failure and to develop effective treatment strategies.
References
Francisqueti-Ferron FV, Nakandakare-Maia ET, Siqueira JS, Ferron AJT, Vieira TA, Bazan SGZ, et al. The role of gut dysbiosis-associated inflammation in heart failure. Rev Assoc Médica Bras 2022;68:1120–4. https://doi.org/10.1590/1806-9282.20220197
Kitai T, Kirsop J, Tang WHW. Exploring the Microbiome in Heart Failure. Curr Heart Fail Rep 2016;13:103–9. https://doi.org/10.1007/s11897-016-0285-9
Li L, Zhong S, Cheng B, Qiu H, Hu Z. Cross-Talk between Gut Microbiota and the Heart: A New Target for the Herbal Medicine Treatment of Heart Failure? Evid Based Complement Alternat Med 2020;2020:1–9. https://doi.org/10.1155/2020/9097821
Lupu VV, Adam Raileanu A, Mihai CM, Morariu ID, Lupu A, Starcea IM, et al. The Implication of the Gut Microbiome in Heart Failure. Cells 2023;12:1158. https://doi.org/10.3390/cells12081158.
Kowalczyk B, Czyż R, Kaźmierska B. Niewydolność Serca - Definicja, Klasyfikacja, Epidemiologia, Objawy I Leczenie = Heart Failure - Definition, Classification, Epidemiology, Symptoms And Treatment. 2016. https://doi.org/10.5281/ZENODO.168089
Murphy SP, Ibrahim NE, Januzzi JL. Heart Failure With Reduced Ejection Fraction: A Review. JAMA 2020;324:488. https://doi.org/10.1001/jama.2020.10262
Wu J, Zheng H, Liu X, Chen P, Zhang Y, Luo J, et al. Prognostic Value of Secreted Frizzled-Related Protein 5 in Heart Failure Patients With and Without Type 2 Diabetes Mellitus. Circ Heart Fail 2020;13:e007054. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007054.
Jia Q, Li H, Zhou H, Zhang X, Zhang A, Xie Y, et al. Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure. Cardiovasc Ther 2019;2019:1–10. https://doi.org/10.1155/2019/5164298
Mu F, Tang M, Guan Y, Lin R, Zhao M, Zhao J, et al. Knowledge Mapping of the Links Between the Gut Microbiota and Heart Failure: A Scientometric Investigation (2006–2021). Front Cardiovasc Med 2022;9:882660. https://doi.org/10.3389/fcvm.2022.882660
Kitai T, Tang WHW. Gut microbiota in cardiovascular disease and heart failure. Clin Sci 2018;132:85–91. https://doi.org/10.1042/CS20171090
Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med 2016;8:51. https://doi.org/10.1186/s13073-016-0307-y
Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLOS Biol 2016;14:e1002533. https://doi.org/10.1371/journal.pbio.1002533
Hufnagl K, Pali-Schöll I, Roth-Walter F, Jensen-Jarolim E. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin Immunopathol 2020;42:75–93. https://doi.org/10.1007/s00281-019-00775-y
Ramakrishna BS. Role of the gut microbiota in human nutrition and metabolism: Role of the gut microbiota. J Gastroenterol Hepatol 2013;28:9–17. https://doi.org/10.1111/jgh.12294
Kataoka K. The intestinal microbiota and its role in human health and disease. J Med Investig JMI 2016;63:27–37. https://doi.org/10.2152/jmi.63.27
Panek-Jeziorna M, Mulak A. The role of bile acids in the pathogenesis of bowel diseases. Postępy Hig Med Dośw 2017;71:0–0. https://doi.org/10.5604/01.3001.0010.3852
Jandhyala SM. Role of the normal gut microbiota. World J Gastroenterol 2015;21:8787. https://doi.org/10.3748/wjg.v21.i29.8787
Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med 2016;22:713–22. https://doi.org/10.1038/nm.4142
Brown JM, Hazen SL. The Gut Microbial Endocrine Organ: Bacterially Derived Signals Driving Cardiometabolic Diseases. Annu Rev Med 2015;66:343–59. https://doi.org/10.1146/annurev-med-060513-093205.
Caesar R, Nygren H, Orešič M, Bäckhed F. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism. J Lipid Res 2016;57:474–81. https://doi.org/10.1194/jlr.M065847
Zakład Biochemii i Żywienia Człowieka, Pomorski Uniwersytet Medyczny w Szczecinie, Szczecin, Polska, Skonieczna-Żydecka K, Łoniewski I, Zakład Biochemii i Żywienia Człowieka, Pomorski Uniwersytet Medyczny w Szczecinie, Szczecin, Polska, Maciejewska D, Zakład Biochemii i Żywienia Człowieka, Pomorski Uniwersytet Medyczny w Szczecinie, Szczecin, Polska, et al. Intestinal microbiota and nutrients as determinants of nervous system function. Part I. Gastrointestinal microbiota. Aktual Neurol 2017;17:181–8. https://doi.org/10.15557/AN.2017.0020
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. Sci Rep 2018;8:635. https://doi.org/10.1038/s41598-017-18756-2
Wang Z, Cai Z, Ferrari MW, Liu Y, Li C, Zhang T, et al. The Correlation between Gut Microbiota and Serum Metabolomic in Elderly Patients with Chronic Heart Failure. Mediators Inflamm 2021;2021:1–13. https://doi.org/10.1155/2021/5587428
Hayashi T, Yamashita T, Takahashi T, Tabata T, Watanabe H, Gotoh Y, et al. Uncovering the Role of Gut Microbiota in Amino Acid Metabolic Disturbances in Heart Failure Through Metagenomic Analysis. Front Cardiovasc Med 2021;8:789325. https://doi.org/10.3389/fcvm.2021.789325
Luedde M, Winkler T, Heinsen F-A, Rühlemann MC, Spehlmann ME, Bajrovic A, et al. Heart failure is associated with depletion of core intestinal microbiota: The intestinal microbiome in heart failure. ESC Heart Fail 2017;4:282–90. https://doi.org/10.1002/ehf2.12155
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:e0174099. https://doi.org/10.1371/journal.pone.0174099
Li L, Zhong S, Hu S, Cheng B, Qiu H, Hu Z. Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats. BMC Microbiol 2021;21:141. https://doi.org/10.1186/s12866-021-02202-5
Tang WHW, Kitai T, Hazen SL. Gut Microbiota in Cardiovascular Health and Disease. Circ Res 2017;120:1183–96. https://doi.org/10.1161/CIRCRESAHA.117.309715
Gątarek P, Kałużna-Czaplińska J. Trimethylamine N-oxide (TMAO) in human health. EXCLI J 20Doc301 ISSN 1611-2156 2021. https://doi.org/10.17179/EXCLI2020-3239
Bhargava S, Merckelbach E, Noels H, Vohra A, Jankowski J. Homeostasis in the Gut Microbiota in Chronic Kidney Disease. Toxins 2022;14:648. https://doi.org/10.3390/toxins14100648
Falony G, Vieira-Silva S, Raes J. Microbiology Meets Big Data: The Case of Gut Microbiota–Derived Trimethylamine. Annu Rev Microbiol 2015;69:305–21. https://doi.org/10.1146/annurev-micro-091014-104422
Koeth RA, Levison BS, Culley MK, Buffa JA, Wang Z, Gregory JC, et al. γ-Butyrobetaine Is a Proatherogenic Intermediate in Gut Microbial Metabolism of L-Carnitine to TMAO. Cell Metab 2014;20:799–812. https://doi.org/10.1016/j.cmet.2014.10.006
Yazaki Y, Aizawa K, Israr MZ, Negishi K, Salzano A, Saitoh Y, et al. Ethnic differences in association of outcomes with trimethylamine N‐oxide in acute heart failure patients. ESC Heart Fail 2020;7:2373–8. https://doi.org/10.1002/ehf2.12777
Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. The Lancet 2000;355:1518–9. https://doi.org/10.1016/S0140-6736(00)02169-3
Carpes LS, Nicoletto BB, Canani LH, Rheinhemer J, Crispim D, Souza GC. Could serum zonulin be an intestinal permeability marker in diabetes kidney disease? PLOS ONE 2021;16:e0253501. https://doi.org/10.1371/journal.pone.0253501
Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Research 2020;9:69. https://doi.org/10.12688/f1000research.20510.1
Yu W, Jiang Y, Xu H, Zhou Y. The Interaction of Gut Microbiota and Heart Failure with Preserved Ejection Fraction: From Mechanism to Potential Therapies. Biomedicines 2023;11:442. https://doi.org/10.3390/biomedicines11020442.
Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol 2020;11:25. https://doi.org/10.3389/fendo.2020.00025
Imran M, Ehrhardt CJ, Bertino MF, Shah MR, Yadavalli VK. Chitosan Stabilized Silver Nanoparticles for the Electrochemical Detection of Lipopolysaccharide: A Facile Biosensing Approach for Gram-Negative Bacteria. Micromachines 2020;11:413. https://doi.org/10.3390/mi11040413
Yamashita T, Yoshida N, Emoto T, Saito Y, Hirata K. Two Gut Microbiota-Derived Toxins Are Closely Associated with Cardiovascular Diseases: A Review. Toxins 2021;13:297. https://doi.org/10.3390/toxins13050297
Niebauer J, Volk H-D, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. The Lancet 1999;353:1838–42. https://doi.org/10.1016/S0140-6736(98)09286-1
Al-Rubaye H, Perfetti G, Kaski J-C. The Role of Microbiota in Cardiovascular Risk: Focus on Trimethylamine Oxide. Curr Probl Cardiol 2019;44:182–96. https://doi.org/10.1016/j.cpcardiol.2018.06.005
Moludi J, Maleki V, Jafari‐Vayghyan H, Vaghef‐Mehrabany E, Alizadeh M. Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics. Clin Exp Pharmacol Physiol 2020;47:927–39. https://doi.org/10.1111/1440-1681.13250
Zmora N, Suez J, Elinav E. You are what you eat: diet, health and the gut microbiota. Nat Rev Gastroenterol Hepatol 2019;16:35–56. https://doi.org/10.1038/s41575-018-0061-2
Rinninella, Cintoni, Raoul, Lopetuso, Scaldaferri, Pulcini, et al. Food Components and Dietary Habits: Keys for a Healthy Gut Microbiota Composition. Nutrients 2019;11:2393. https://doi.org/10.3390/nu11102393
García-Montero C, Fraile-Martínez O, Gómez-Lahoz AM, Pekarek L, Castellanos AJ, Noguerales-Fraguas F, et al. Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota–Immune System Interplay. Implications for Health and Disease. Nutrients 2021;13:699. https://doi.org/10.3390/nu13020699
Merra G, Noce A, Marrone G, Cintoni M, Tarsitano MG, Capacci A, et al. Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients 2020;13:7. https://doi.org/10.3390/nu13010007
Aleixandre A, Miguel M. Dietary fiber and blood pressure control. Food Funct 2016;7:1864–71. https://doi.org/10.1039/C5FO00950B
Berger S, Raman G, Vishwanathan R, Jacques PF, Johnson EJ. Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 2015;102:276–94. https://doi.org/10.3945/ajcn.114.100305
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559–63. https://doi.org/10.1038/nature12820
Kim K-A, Gu W, Lee I-A, Joh E-H, Kim D-H. High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway. PLoS ONE 2012;7:e47713. https://doi.org/10.1371/journal.pone.0047713
Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 2017;551:585–9. https://doi.org/10.1038/nature24628
Guan X, Sun Z. The Role of Intestinal Flora and Its Metabolites in Heart Failure. Infect Drug Resist 2023; Volume 16:51–64. https://doi.org/10.2147/IDR.S390582
Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol 2019;16:605–16. https://doi.org/10.1038/s41575-019-0173-3
Gerritsen J, Smidt H, Rijkers GT, De Vos WM. Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr 2011;6:209–40. https://doi.org/10.1007/s12263-011-0229-7
Oniszczuk A, Oniszczuk T, Gancarz M, Szymańska J. Role of Gut Microbiota, Probiotics and Prebiotics in the Cardiovascular Diseases. Molecules 2021;26:1172. https://doi.org/10.3390/molecules26041172
Gan XT, Ettinger G, Huang CX, Burton JP, Haist JV, Rajapurohitam V, et al. Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat. Circ Heart Fail 2014;7:491–9. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000978
Vlasov AA, Shperling MI, Terkin DA, Bystrova OV, Osipov GA, Salikova SP, et al. Effect of Prebiotic Complex on Gut Microbiota and Endotoxemia in Female Rats with Modeled Heart Failure. Bull Exp Biol Med 2020;168:435–8. https://doi.org/10.1007/s10517-020-04726-8
Conraads VM, Jorens PG, De Clerck LS, Van Saene HK, Ieven MM, Bosmans JM, et al. Selective intestinal decontamination in advanced chronic heart failure: a pilot trial. Eur J Heart Fail 2004;6:483–91. https://doi.org/10.1016/j.ejheart.2003.12.004
Ma C, Han M, Heinrich B, Fu Q, Zhang Q, Sandhu M, et al. Gut microbiome–mediated bile acid metabolism regulates liver cancer via NKT cells. Science 2018;360:eaan5931. https://doi.org/10.1126/science.aan5931
Wong AYS, Root A, Douglas IJ, Chui CSL, Chan EW, Ghebremichael-Weldeselassie Y, et al. Cardiovascular outcomes associated with use of clarithromycin: population based study. BMJ 2016:h6926. https://doi.org/10.1136/bmj.h6926
Korpela K, Salonen A, Virta LJ, Kekkonen RA, Forslund K, Bork P, et al. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun 2016;7:10410. https://doi.org/10.1038/ncomms10410
Reijnders D, Goossens GH, Hermes GDA, Neis EPJG, van der Beek CM, Most J, et al. Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial. Cell Metab 2016;24:63–74. https://doi.org/10.1016/j.cmet.2016.06.016
Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile Colitis. N Engl J Med 1994;330:257–62. https://doi.org/10.1056/NEJM199401273300406
Jie Z, Xia H, Zhong S-L, Feng Q, Li S, Liang S, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun 2017;8:845. https://doi.org/10.1038/s41467-017-00900-1
Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol 2016;13:508–16. https://doi.org/10.1038/nrgastro.2016.98
Baunwall SMD, Lee MM, Eriksen MK, Mullish BH, Marchesi JR, Dahlerup JF, et al. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis. EClinicalMedicine 2020;29–30:100642. https://doi.org/10.1016/j.eclinm.2020.100642
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Joanna Osiak, Łukasz Wołowiec, Xawery Żukow, Dagmara Fydrych, Albert Jasniak, Kinga Gawłowska, Agata Staniewska, Grzegorz Grześk
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 356
Number of citations: 0
