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Probiotics as potential treatments to reduce myocardial remodelling and heart failure via the gut-heart axis: State-of-the-art review

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Abstract

Probiotics are considered to represent important modulators of gastrointestinal health through increased colonization of beneficial bacteria thus altering the gut microflora. Although these beneficial effects of probiotics are now widely recognized, emerging evidence suggests that alterations in the gut microflora also affect numerous other organ systems including the heart through a process generally referred to as the gut-heart axis. Moreover, cardiac dysfunction such as that seen in heart failure can produce an imbalance in the gut flora, known as dysbiosis, thereby further contributing to cardiac remodelling and dysfunction. The latter occurs by the production of gut-derived pro-inflammatory and pro-remodelling factors which exacerbate cardiac pathology. One of the key contributors to gut-dependent cardiac pathology is trimethylamine N-oxide (TMAO), a choline and carnitine metabolic by-product first synthesized as trimethylamine which is then converted into TMAO by a hepatic flavin-containing monooxygenase. The production of TMAO is particularly evident with regular western diets containing high amounts of both choline and carnitine. Dietary probiotics have been shown to reduce myocardial remodelling and heart failure in animal models although the precise mechanisms for these effects are not completely understood. A large number of probiotics have been shown to possess a reduced capacity to synthesize gut-derived trimethylamine and therefore TMAO thereby suggesting that inhibition of TMAO is a factor mediating the beneficial cardiac effects of probiotics. However, other potential mechanisms may also be important contributing factors. Here, we discuss the potential benefit of probiotics as effective therapeutic tools for attenuating myocardial remodelling and heart failure.

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References

  1. Cleland JGF, van Veldhuisen DJ, Ponikowski P (2019) The year in cardiology 2018: heart failure. Eur Heart J 40:651–661. https://doi.org/10.1093/eurheartj/ehz010

    Article  PubMed  Google Scholar 

  2. Inamdar AA, Inamdar AC (2016) Heart failure: Diagnosis, management and utilization. J Clin Med 5:62. https://doi.org/10.3390/jcm5070062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kim DH, Chien F-J, Eisen HJ (2017) Pharmacologic management for heart failure and emerging therapies. Curr Cardiol Rep 19:94. https://doi.org/10.1007/s11886-017-0899-x

    Article  PubMed  Google Scholar 

  4. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (2022) 2022 AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of cardiology/american heart association joint committee on clinical practice guidelines. Circulation 145:e876–e894. https://doi.org/10.1161/CIR.0000000000001062

    Article  PubMed  Google Scholar 

  5. Ziaeian B, Fonarow GC (2016) Epidemiology and aetiology of heart failure. Nat Rev Cardiol 13:368–378. https://doi.org/10.1038/nrcardio.2016.25

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tomasoni D, Fonarow GC, Adamo M, Anker SD, Butler J, Coats AJS, Filippatos G, Greene SJ, McDonagh TA, Ponikowski P, Rosano G, Seferovic P, Vaduganathan M, Voors AA, Metra M (2022) Sodium-glucose co-transporter 2 inhibitors as an early, first-line therapy in patients with heart failure and reduced ejection fraction. Eur J Heart Fail 24:431–441. https://doi.org/10.1002/ejhf.2397

    Article  CAS  PubMed  Google Scholar 

  7. Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, Devore AD, Yancy CW, Fonarow GC (2017) Heart Failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol 70:2476–2486. https://doi.org/10.1016/j.jacc.2017.08.074

    Article  PubMed  Google Scholar 

  8. Lancet T (2018) Heart failure: the need for improved treatment and care. The Lancet 392:451. https://doi.org/10.1016/S0140-6736(18)31737-9

    Article  Google Scholar 

  9. Rodrigues PG, Leite-Moreira AF, Falcão-Pires I (2016) Myocardial reverse remodeling: how far can we rewind? Am J Physiol Heart Circ Physiol 310:H1402–H1422. https://doi.org/10.1152/ajpheart.00696.2015

    Article  PubMed  Google Scholar 

  10. Bhatt AS, Ambrosy AP, Velazquez EJ (2017) Adverse remodeling and reverse remodeling after myocardial infarction. Curr Cardiol Rep 19:71. https://doi.org/10.1007/s11886-017-0876-4

    Article  PubMed  Google Scholar 

  11. Karmazyn M, Gan XT (2017) Treatment of the cardiac hypertrophic response and heart failure with ginseng, ginsenosides, and ginseng-related products. Can J Physiol Pharmacol 95:1170–1176. https://doi.org/10.1139/cjpp-2017-0092

    Article  CAS  PubMed  Google Scholar 

  12. Mashour NH, Lin GI, Frishman WH (1998) Herbal medicine for the treatment of cardiovascular disease: clinical considerations. Arch Int Med 158:2225–2234. https://doi.org/10.1001/archinte.158.20.2225

    Article  CAS  Google Scholar 

  13. Puebla-Barragan S, Reid G (2019) Forty-five-year evolution of probiotic therapy. Microb Cell 6:184–196. https://doi.org/10.15698/mic2019.04.673

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mackowiak PA (2013) Recycling Metchnikoff: probiotics, the intestinal microbiome and the quest for long life. Front Public Health 1:52. https://doi.org/10.3389/fpubh.2013.00052

    Article  PubMed  PubMed Central  Google Scholar 

  15. Krawczyk RT, Banaszkiewicz A (2021) Dr. Józef Brudziński - the true “Father of probiotics.” Benef Microbes 12:211–213. https://doi.org/10.3920/BM2020.0201

    Article  CAS  PubMed  Google Scholar 

  16. Ozen M (2015) Dinleyici EC (2015) The history of probiotics: the untold story. Benef Microbes 6:159–165. https://doi.org/10.3920/BM2014.0103

    Article  CAS  PubMed  Google Scholar 

  17. Gasbarrini G, Bonvicini F, Gramenzi A (2016) Probiotics History. J Clin Gastroenterol 50 Suppl 2. Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13–15, 2015:S116-S119. https://doi.org/10.1097/MCG.0000000000000697

  18. Santacroce L, Charitos IA, Bottalico L (2019) A successful history: probiotics and their potential as antimicrobials. Expert Rev Anti Infect Ther 17:635–645. https://doi.org/10.1080/14787210.2019.1645597

    Article  CAS  PubMed  Google Scholar 

  19. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME (2014) Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11:506–514. https://doi.org/10.1038/nrgastro.2014.66

    Article  PubMed  Google Scholar 

  20. Gibson GR, Probert HM, Loo JV, Rastall RA, Roberfroid MB (2004) Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev 17:259–275. https://doi.org/10.1079/NRR200479

    Article  CAS  PubMed  Google Scholar 

  21. Valcheva R, Dieleman LA (2016) Prebiotics: Definition and protective mechanisms. Best Pract Res Clin Gastroenterol 30:27–37. https://doi.org/10.1016/j.bpg.2016.02.008

    Article  CAS  PubMed  Google Scholar 

  22. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, Berenjian A, Ghasemi Y (2019) Prebiotics: Definition, types, sources, mechanisms, and clinical applications. Foods 8:92. https://doi.org/10.3390/foods8030092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Swanson KS, Gibson GR, Hutkins R, Reimer RA, Reid G, Verbeke K, Scott KP, Holscher HD, Azad MB, Delzenne NM, Sanders ME (2020) The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol 17:687–701. https://doi.org/10.1038/s41575-020-0344-2

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA (2019) Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol 16:605–616. https://doi.org/10.1038/s41575-019-0173-3(Authorcorrection.In:NatRevGastroenterolHepatol(2019)16:642)

    Article  PubMed  Google Scholar 

  25. Zagórska A, Marcinkowska M, Jamrozik M, Wiśniowska B, Paśko P (2020) From probiotics to psychobiotics - the gut-brain axis in psychiatric disorders. Benef Microbes 11:717–732. https://doi.org/10.3920/BM2020.0063

    Article  PubMed  Google Scholar 

  26. Gazerani P (2019) Probiotics for Parkinson’s Disease. Int J Mol Sci 20:4121. https://doi.org/10.3390/ijms20174121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang L, Guo MJ, Gao Q, Yang JF, Yang L, Pang XL, Xiang XJ (2018) The effects of probiotics on total cholesterol: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 97:e9679. https://doi.org/10.1097/MD.0000000000009679

    Article  CAS  PubMed  Google Scholar 

  28. Gómez-Guzmán M, Toral M, Romero M, Jiménez R, Galindo P, Sánchez M, Zarzuelo MJ, Olivares M, Gálvez J, Duarte J (2015) Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res 59:2326–2336. https://doi.org/10.1002/mnfr.201500290

    Article  CAS  PubMed  Google Scholar 

  29. Robles-Vera I, Toral M, de la Visitación N, Sánchez M, Gómez-Guzmán M, Romero M, Yang T, Izquierdo-Garcia JL, Jiménez R, Ruiz-Cabello J, Guerra-Hernández E, Raizada MK, Pérez-Vizcaíno F, Duarte J (2020) Probiotics prevent dysbiosis and the rise in blood pressure in genetic hypertension: Role of short-chain fatty acids. Mol Nutr Food Res 64:e1900616. https://doi.org/10.1002/mnfr.201900616

    Article  CAS  PubMed  Google Scholar 

  30. Kong CY, Li ZM, Mao YQ, Chen HL, Hu W, Han B, Wang LS (2021) Probiotic yogurt blunts the increase of blood pressure in spontaneously hypertensive rats via remodeling of the gut microbiota. Food Funct 12:9773–9783. https://doi.org/10.1039/d1fo01836a

    Article  CAS  PubMed  Google Scholar 

  31. do Nascimento LCP, de Souza EL, de Luna Freire MO, de Andrade Braga V, de Albuqeurque TMR, Lagranha CJ, de Brito Alves JL (2022) Limosilactobacillus fermentum prevents gut-kidney oxidative damage and the rise in blood pressure in male rat offspring exposed to a maternal high-fat diet. J Dev Orig Health Dis 13: 719–726. doi:https://https://doi.org/10.1017/S2040174422000198. Erratum in: J Dev Orig Health Dis (2022) 13: 817. PMID: 35437140

  32. Robles-Vera I, de la Visitación N, Toral M, Sánchez M, Romero M, Gómez-Guzmán M, Yang T, Izquierdo-García JL, Guerra-Hernández E, Ruiz-Cabello J, Raizada MK, Pérez-Vizcaíno F, Jiménez R, Duarte J (2020) Probiotic Bifidobacterium breve prevents DOCA-salt hypertension. FASEB J 34:13626–13640. https://doi.org/10.1096/fj.202001532R

    Article  CAS  PubMed  Google Scholar 

  33. Ganesh BP, Nelson JW, Eskew JR, Ganesan A, Ajami NJ, Petrosino JF, Bryan RM Jr, Durgan DJ (2018) Prebiotics, probiotics, and acetate supplementation prevent hypertension in a model of obstructive sleep apnea. Hypertension 72:1141–1150. https://doi.org/10.1161/HYPERTENSIONAHA.118.11695

    Article  CAS  PubMed  Google Scholar 

  34. Chi C, Li C, Wu D, Buys N, Wang W, Fan H, Sun J (2020) Effects of probiotics on patients with hypertension: a systematic review and meta-analysis. Curr Hypertens Rep 225:34. https://doi.org/10.1007/s11906-020-01042-4

    Article  Google Scholar 

  35. Nagatomo Y, Tang WH (2015) Intersections between microbiome and heart failure: revisiting the gut hypothesis. J Card Fail 21:973–980. https://doi.org/10.1016/j.cardfail.2015.09.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kamo T, Akazawa H, Suzuki JI, Komuro I (2017) Novel concept of a heart-gut axis in the pathophysiology of heart failure. Korean Circ J 47:663–669. https://doi.org/10.4070/kcj.2017.0028

    Article  PubMed  PubMed Central  Google Scholar 

  37. Tang WHW, Bäckhed F, Landmesser U, Hazen SL (2019) Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol 73:2089–2105. https://doi.org/10.1016/j.jacc.2019.03.024

    Article  PubMed  PubMed Central  Google Scholar 

  38. Luedde M, Winkler T, Heinsen FA, Rühlemann MC, Spehlmann ME, Bajrovic A, Lieb W, Franke A, Ott SJ, Frey N (2017) Heart failure is associated with depletion of core intestinal microbiota. ESC Heart Fail 4:282–290. https://doi.org/10.1002/ehf2.12155

    Article  PubMed  PubMed Central  Google Scholar 

  39. Li L, Zhong SJ, Hu SY, Cheng B, Qiu H, Hu ZX (2021) Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats. BMC Microbiol 21:141. https://doi.org/10.1186/s12866-021-02202-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mamic P, Chaikijurajai T, Tang WHW (2021) Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review. J Mol Cell Cardiol 152:105–117. https://doi.org/10.1016/j.yjmcc.2020.12.001

    Article  CAS  PubMed  Google Scholar 

  41. Sandek A, Swidsinski A, Schroedl W, Watson A, Valentova M, Herrmann R, Scherbakov N, Cramer L, Rauchhaus M, Grosse-Herrenthey A, Krueger M, von Haehling S, Doehner W, Anker SD, Bauditz J (2014) Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia. J Am Coll Cardiol 64:1092–1102. https://doi.org/10.1016/j.jacc.2014.06.1179

    Article  PubMed  Google Scholar 

  42. Arutyunov GP, Kostyukevich OI, Serov RA, Rylova NV, Bylova NA (2008) Collagen accumulation and dysfunctional mucosal barrier of the small intestine in patients with chronic heart failure. Int J Cardiol 125:240–245. https://doi.org/10.1016/j.ijcard.2007.11.103

    Article  PubMed  Google Scholar 

  43. Tang TWH, Chen HC, Chen CY, Yen CYT, Lin CJ, Prajnamitra RP, Chen LL, Ruan SC, Lin JH, Lin PJ, Lu HH, Kuo CW, Chang CM, Hall AD, Vivas EI, Shui JW, Chen P, Hacker TA, Rey FE, Kamp TJ, Hsieh PCH (2019) Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation 139:647–659. https://doi.org/10.1161/CIRCULATIONAHA.118.035235

    Article  CAS  PubMed  Google Scholar 

  44. Hardin SJ, Singh M, Eyob W, Molnar JC, Homme RP, George AK, Tyagi SC (2019) Diet-induced chronic syndrome, metabolically transformed trimethylamine-N-oxide, and the cardiovascular functions. Rev Cardiovasc Med 20:121–128. https://doi.org/10.31083/j.rcm.2019.03.518

    Article  PubMed  Google Scholar 

  45. Din AU, Hassan A, Zhu Y, Yin T, Gregersen H, Wang G (2019) Amelioration of TMAO through probiotics and its potential role in atherosclerosis. Appl Microbiol Biotechnol 103:9217–9228. https://doi.org/10.1007/s00253-019-10142-4

    Article  CAS  PubMed  Google Scholar 

  46. Witkowski M, Weeks TL, Hazen SL (2020) Gut microbiota and cardiovascular disease. Circ Res 127:553–570. https://doi.org/10.1161/CIRCRESAHA.120.316242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vourakis M, Mayer G, Rousseau G (2021) The role of gut microbiota on cholesterol metabolism in atherosclerosis. Int J Mol Sci 22:8074. https://doi.org/10.3390/ijms22158074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Duttaroy AK (2021) Role of gut microbiota and their metabolites on atherosclerosis, hypertension and human blood platelet function: A review. Rev Nutr 13:144. https://doi.org/10.3390/nu13010144

    Article  CAS  Google Scholar 

  49. Zeisel SH, Warrier M (2017) Trimethylamine N-oxide, the microbiome, and heart and kidney disease. Ann Rev Nutr 37:157–181. https://doi.org/10.1146/annurev-nutr-071816-064732

    Article  CAS  Google Scholar 

  50. Boutagy NE, Neilson AP, Osterberg KL, Smithson AT, Englund TR, Davy BM, Hulver MW, Davy KP (2015) Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet. Obesity (Silver Spring) 23:2357–2363. https://doi.org/10.1002/oby.21212

    Article  CAS  PubMed  Google Scholar 

  51. Chen K, Zheng X, Feng M, Li D, Zhang H (2017) Gut microbiota-dependent metabolite trimethylamine N-oxide contributes to cardiac dysfunction in western diet-induced obese mice. Front Physiol 8:139. https://doi.org/10.3389/fphys.2017.00139

    Article  PubMed  PubMed Central  Google Scholar 

  52. Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115:1285–1295. https://doi.org/10.1161/CIRCULATIONAHA.106.652859

    Article  PubMed  Google Scholar 

  53. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376. https://doi.org/10.1038/288373a0

    Article  CAS  PubMed  Google Scholar 

  54. Fleming I, Busse R (1999) NO: the primary EDRF. J Mol Cell Cardiol 31:5–14. https://doi.org/10.1006/jmcc.1998.0839

    Article  CAS  PubMed  Google Scholar 

  55. Sun X, Jiao X, Ma Y, Liu Y, Zhang L, He Y, Chen Y (2016) Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem Biophys Res Commun 481:63–70. https://doi.org/10.1016/j.bbrc.2016.11.017

    Article  CAS  PubMed  Google Scholar 

  56. Querio G, Antoniotti S, Geddo F, Levi R, Gallo MP (2022) Trimethylamine N-oxide (TMAO) impairs purinergic induced intracellular calcium increase and nitric oxide release in endothelial cells. Int Journal Mol Sci 23:3982. https://doi.org/10.3390/ijms23073982

    Article  CAS  Google Scholar 

  57. Li T, Chen Y, Gua C, Li X (2017) Elevated circulating trimethylamine N-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Front Physiol 8:350. https://doi.org/10.3389/fphys.2017.00350

    Article  PubMed  PubMed Central  Google Scholar 

  58. Li Z, Wu Z, Yan J, Liu H, Liu Q, Deng Y, Ou C, Chen M (2019) Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis. Lab Invest 99:346–357. https://doi.org/10.1038/s41374-018-0091-y

    Article  CAS  PubMed  Google Scholar 

  59. Schultz Jel J, Witt SA, Glascock BJ, Nieman ML, Reiser PJ, Nix SL, Kimball TR, Doetschman T (2002) TGF-β1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J Clin Invest 109:787–796. https://doi.org/10.1172/JCI14190

    Article  PubMed  Google Scholar 

  60. Li X, Fan Z, Cui J, Li D, Lu J, Cui X, Xie L, Wu Y, Lin Q, Li Y (2022) Trimethylamine N-oxide in heart failure: a meta-analysis of prognostic value. Front Cardiovasc Med 9:817396. https://doi.org/10.3389/fcvm.2022.817396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Tang WH, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, Wu Y, Hazen SL (2014) Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol 64:1908–1914. https://doi.org/10.1016/j.jacc.2014.02.617

    Article  CAS  PubMed  Google Scholar 

  62. Salzano A, Cassambai S, Yazaki Y, Israr MZ, Bernieh D, Wong M, Suzuki T (2022) The gut axis involvement in heart failure: focus on trimethylamine N-oxide. Cardiol Clin 40:161–169. https://doi.org/10.1016/j.ccl.2021.12.004

    Article  PubMed  Google Scholar 

  63. Israr MZ, Zhan H, Salzano A, Voors AA, Cleland JG, Anker SD, Metra M, van Veldhuisen DJ, Lang CC, Zannad F, Samani NJ, Ng LL, Suzuki T, BIOSTAT-CHF investigators (2022) Surrogate markers of gut dysfunction are related to heart failure severity and outcome-from the BIOSTAT-CHF consortium. Am Heart J 248:108–119. https://doi.org/10.1016/j.ahj.2022.03.002

    Article  CAS  PubMed  Google Scholar 

  64. Konieczny R, Żurawska-Płaksej E, Kaaz K, Czapor-Irzabek H, Bombała W, Mysiak A, Kuliczkowski W (2022) All-cause mortality and trimethylamine-N-oxide levels in patients with cardiovascular disease. Cardiology 147:443–452. https://doi.org/10.1159/000525972

    Article  CAS  PubMed  Google Scholar 

  65. Zong X, Fan Q, Yang Q, Pan R, Zhuang L, Xi R, Zhang R, Tao R (2022) Trimethyllysine, a trimethylamine N-oxide precursor, predicts the presence, severity, and prognosis of heart failure. Front Cardiovasc Med 9:907997. https://doi.org/10.3389/fcvm.2022.907997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wang G, Kong B, Shuai W, Fu H, Jiang X, Huang H (2020) 3,3-Dimethyl-1-butanol attenuates cardiac remodeling in pressure-overload-induced heart failure mice. J Nutr Biochem 78:108341. https://doi.org/10.1016/j.jnutbio.2020.108341

    Article  CAS  PubMed  Google Scholar 

  67. Organ CL, Otsuka H, Bhushan S, Wang Z, Bradley J, Trivedi R, Polhemus DJ, Tang WH, Wu Y, Hazen SL, Lefer DJ (2016) Choline diet and its gut microbe-derived metabolite, trimethylamine N-oxide, exacerbate pressure overload-induced heart failure. Circ Heart Fail 9:e002314. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002314

    Article  CAS  PubMed  Google Scholar 

  68. Zou D, Li Y, Sun G (2021) Attenuation of circulating trimethylamine N-oxide prevents the progression of cardiac and renal dysfunction in a rat model of chronic cardiorenal syndrome. Front Pharmacol 12:751380. https://doi.org/10.3389/fphar.2021.751380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yuzefpolskaya M, Bohn B, Javaid A, Mondellini GM, Braghieri L, Pinsino A, Onat D, Cagliostro B, Kim A, Takeda K, Naka Y, Farr M, Sayer GT, Uriel N, Nandakumar R, Mohan S, Colombo PC, Demmer RT (2021) Levels of trimethylamine N-oxide remain elevated long term after left ventricular assist device and heart transplantation and are independent from measures of inflammation and gut dysbiosis. Circ Heart Fail 14:e007909. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007909

    Article  PubMed  PubMed Central  Google Scholar 

  70. Yoshida Y, Shimizu I, Shimada A, Nakahara K, Yanagisawa S, Kubo M, Fukuda S, Ishii C, Yamamoto H, Ishikawa T, Kano K, Aoki J, Katsuumi G, Suda M, Ozaki K, Yoshida Y, Okuda S, Ohta S, Okamoto S, Minokoshi Y, Oda K, Sasaoka T, Abe M, Sakimura K, Kubota Y, Yoshimura N, Kajimura S, Zuriaga M, Walsh K, Soga T, Minamino T (2022) Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism. Sci Rep 12:14883. https://doi.org/10.1038/s41598-022-19245-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Li X, Sun Y, Zhang X, Wang J (2019) 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. Mol Med Rep 20:779–786. https://doi.org/10.3892/mmr.2019.10297

    Article  CAS  PubMed  Google Scholar 

  72. Massagué J, Wotton D (2000) Transcriptional control by the TGF-β/Smad signaling system. EMBO J 19:1745–1754. https://doi.org/10.1093/emboj/19.8.1745

    Article  PubMed  PubMed Central  Google Scholar 

  73. Huc T, Drapala A, Gawrys M, Konop M, Bielinska K, Zaorska E, Samborowska E, Wyczalkowska-Tomasik A, Pączek L, Dadlez M, Ufnal M (2018) Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats. Am J Physiol Heart Circ Physiol 315:H1805–H1820. https://doi.org/10.1152/ajpheart.00536.2018

    Article  CAS  PubMed  Google Scholar 

  74. Marques FZ, Mackay CR, Kaye DM (2018) Beyond gut feelings: how the gut microbiota regulates blood pressure. Nat Rev Cardiol 15:20–32. https://doi.org/10.1038/nrcardio.2017.120

    Article  PubMed  Google Scholar 

  75. Naqvi S, Asar TO, Kumar V, Al-Abbasi FA, Alhayyani S, Kamal MA, Anwar F (2021) A cross-talk between gut microbiome, salt and hypertension. Biomed Pharmacother 134:111156. https://doi.org/10.1016/j.biopha.2020.111156

    Article  CAS  PubMed  Google Scholar 

  76. Liu G, Cheng J, Zhang T, Shao Y, Chen X, Han L, Zhu R, Wu B (2022) Inhibition of microbiota-dependent trimethylamine N-oxide production ameliorates high salt diet-induced sympathetic excitation and hypertension in rats by attenuating central neuroinflammation and oxidative stress. Front Pharmacol 13:856914. https://doi.org/10.3389/fphar.2022.856914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Qiu L, Yang D, Tao X, Yu J, Xiong H, Wei H (2017) Enterobacter aerogenes ZDY01 attenuates choline-induced trimethylamine N-oxide levels by remodeling gut microbiota in mice. J Microbiol Biotechnol 27:1491–1499. https://doi.org/10.4014/jmb.1703.03039

    Article  CAS  PubMed  Google Scholar 

  78. Qiu L, Tao X, Xiong H, Yu J, Wei H (2018) Lactobacillus plantarum ZDY04 exhibits a strain-specific property of lowering TMAO via the modulation of gut microbiota in mice. Food Funct 9:4299–4309. https://doi.org/10.1039/c8fo00349a

    Article  CAS  PubMed  Google Scholar 

  79. Wang Q, Guo M, Liu Y, Xu M, Shi L, Li X, Zhao J, Zhang H, Wang G, Chen W (2022) Bifidobacterium breve and Bifidobacterium longum attenuate choline-induced plasma trimethylamine N-oxide production by modulating gut microbiota in mice. Nutrients 14:1222. https://doi.org/10.3390/nu14061222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Tungsanga S, Panpetch W, Bhunyakarnjanarat T, Udompornpitak K, Katavetin P, Chancharoenthana W, Chatthanathon P, Somboonna N, Tungsanga K, Tumwasorn S, Leelahavanichkul A (2022) Uremia-induced gut barrier defect in 5/6 nephrectomized mice is worsened by Candida administration through a synergy of uremic toxin, lipopolysaccharide, and (1➔3)-β-D-glucan, but is attenuated by Lacticaseibacillus rhamnosus L34. Int J Mol Sci 23:2511. https://doi.org/10.3390/ijms23052511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Miao L, Du J, Chen Z, Shi D, Qu H (2021) Effects of microbiota-driven therapy on circulating trimethylamine-N-oxide metabolism: A systematic review and meta-analysis. Front Cardiovasc Med 8:710567. https://doi.org/10.3389/fcvm.2021.710567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Koppinger MP, Lopez-Pier MA, Skaria R, Harris PR, Konhilas JP (2020) Lactobacillus reuteri attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow. Am J Physiol Heart Circ Physiol 319:H32–H41. https://doi.org/10.1152/ajpheart.00569.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Danilo CA, Constantopoulos E, McKee LA, Chen H, Regan JA, Lipovka Y, Lahtinen S, Stenman LK, Nguyen TV, Doyle KP, Slepian MJ, Khalpey ZI, Konhilas JP (2017) Bifidobacterium animalis subsp. lactis 420 mitigates the pathological impact of myocardial infarction in the mouse. Benef Microbes 8:257–269. https://doi.org/10.3920/BM2016.0119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Rafiee P, Gross GJ, Salzman NH, Baker JE (2012) Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J 26:1727–1735. https://doi.org/10.1096/fj.11-197921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Stone GW, Selker HP, Thiele H, Patel MR, Udelson JE, Ohman EM, Maehara A, Eitel I, Granger CB, Jenkins PL, Nichols M, Ben-Yehuda O (2016) Relationship between infarct size and outcomes following primary PCI: Patient-level analysis from 10 randomized trials. J Am Coll Cardiol 67:1674–1683. https://doi.org/10.1016/j.jacc.2016.01.069

    Article  PubMed  Google Scholar 

  86. Selker HP, Udelson JE, Ruthazer R, D’Agostino RB, Nichols M, Ben-Yehuda O, Eitel I, Granger CB, Jenkins P, Maehara A, Patel MR, Ohman EM, Thiele H, Stone GW (2017) Relationship between therapeutic effects on infarct size in acute myocardial infarction and therapeutic effects on 1-year outcomes: A patient-level analysis of randomized clinical trials. Am Heart J 188:18–25. https://doi.org/10.1016/j.ahj.2017.02.028

    Article  PubMed  Google Scholar 

  87. Cookson TA (2021) Bacterial-induced blood pressure reduction: Mechanisms for the treatment of hypertension via the gut. Front Cardiovasc Med 8:721393. https://doi.org/10.3389/fcvm.2021.721393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Yan D, Sun Y, Zhou X, Si W, Liu J, Li M, Wu M (2022) Regulatory effect of gut microbes on blood pressure. Animal Model Exp Med. https://doi.org/10.1002/ame2.12233

    Article  PubMed  PubMed Central  Google Scholar 

  89. Höcht C, Allo MA, Polizio AH, Morettón MA, Carranza A, Chiappetta DA, Choi MR (2022) New and developing pharmacotherapies for hypertension. Expert Rev Cardiovasc Ther 20:647–666. https://doi.org/10.1080/14779072.2022.2105204

    Article  CAS  PubMed  Google Scholar 

  90. Gan XT, Ettinger G, Huang CX, Burton JP, Haist JV, Rajapurohitam V, Sidaway JE, Martin G, Gloor GB, Swann JR, Reid G, Karmazyn M (2014) Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail 7:491–499. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000978

    Article  PubMed  Google Scholar 

  91. Karmazyn M, Gan XT, Rajapurohitam V (2013) The potential contribution of circulating and locally produced leptin to cardiac hypertrophy and failure. Can J Physiol Pharmacol 91:883–888. https://doi.org/10.1139/cjpp-2013-0057

    Article  CAS  PubMed  Google Scholar 

  92. Park M, Sweeney G (2013) Direct effects of adipokines on the heart: focus on adiponectin. Heart Fail Rev 18:631–644. https://doi.org/10.1007/s10741-012-9337-8

    Article  CAS  PubMed  Google Scholar 

  93. Ten Hove M, Chan S, Lygate C, Monfared M, Boehm E, Hulbert K, Watkins H, Clarke K, Neubauer S (2005) Mechanisms of creatine depletion in chronically failing rat heart. J Mol Cell Cardiol 38:309–313. https://doi.org/10.1016/j.yjmcc.2004.11.016

    Article  CAS  PubMed  Google Scholar 

  94. Neubauer S, Remkes H, Spindler M, Horn M, Wiesmann F, Prestle J, Walzel B, Ertl G, Hasenfuss G, Wallimann T (1999) Downregulation of the Na+-creatine cotransporter in failing human myocardium and in experimental heart failure. Circulation 100:1847–1850. https://doi.org/10.1161/01.cir.100.18.1847

    Article  CAS  PubMed  Google Scholar 

  95. Huxtable RJ (1993) Taurine and the heart. Cardiovasc Res 27:1136–1137. https://doi.org/10.1093/cvr/27.6.1136a

    Article  CAS  PubMed  Google Scholar 

  96. Schaffer SW, Jong CJ, Ramila KC, Azuma J (2010) Physiological roles of taurine in heart and muscle. J Biomedical Sci. https://doi.org/10.1186/1423-0127-17-S1-S2

    Article  Google Scholar 

  97. Azuma M, Takahashi K, Fukuda T, Ohyabu Y, Yamamoto I, Kim S, Iwao H, Schaffer SW, Azuma J (2000) Taurine attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac myocytes. Eu J Pharmacol 403:181–188. https://doi.org/10.1016/s0014-2999(00)00483-0

    Article  CAS  Google Scholar 

  98. Liu J, Ai Y, Niu X, Shang F, Li Z, Liu H, Li W, Ma W, Chen R, Wei T, Li X, Li X (2020) Taurine protects against cardiac dysfunction induced by pressure overload through SIRT1-p53 activation. Chem Biol Interact 317:108972. https://doi.org/10.1016/j.cbi.2020.108972

    Article  CAS  PubMed  Google Scholar 

  99. Bkaily G, Simon Y, Normand A, Jazzar A, Najibeddine H, Khalil A, Jacques D (2022) Short-Communication: Short-term treatment with taurine prevents the development of cardiac hypertrophy and early death in hereditary cardiomyopathy of the hamster and is sex-dependent. Nutrients 14:3287. https://doi.org/10.3390/nu14163287

    Article  PubMed  PubMed Central  Google Scholar 

  100. Beyranvand MR, Khalafi MK, Roshan VD, Choobineh S, Parsa SA, Piranfar MA (2011) Effect of taurine supplementation on exercise capacity of patients with heart failure. J Cardiol 57:333–337. https://doi.org/10.1016/j.jjcc.2011.01.007

    Article  PubMed  Google Scholar 

  101. Ettinger G, Burton JP, Gloor GB, Reid G (2017) Lactobacillus rhamnosus GR-1 attenuates induction of hypertrophy in cardiomyocytes but not through secreted protein MSP-1 (p75). PLoS ONE 12:e0168622. https://doi.org/10.1371/journal.pone.0168622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Chiang CJ, Chao YP, Ali A, Day CH, Ho TJ, Wang PN, Lin SC, Padma VV, Kuo WW, Huang CY (2021) Probiotic Escherichia coli Nissle inhibits IL-6 and MAPK-mediated cardiac hypertrophy during STZ-induced diabetes in rats. Benef Microbes 12:283–293. https://doi.org/10.3920/BM2020.0094

    Article  CAS  PubMed  Google Scholar 

  103. Chiang CJ, Tsai BC, Lu TL, Chao YP, Day CH, Ho TJ, Wang PN, Lin SC, Padma VV, Kuo WW, Huang CY (2021) Diabetes-induced cardiomyopathy is ameliorated by heat-killed Lactobacillus reuteri GMNL-263 in diabetic rats via the repression of the toll-like receptor 4 pathway. Eur J Nutr 60:3211–3223. https://doi.org/10.1007/s00394-020-02474-z

    Article  CAS  PubMed  Google Scholar 

  104. Hu Y, Pan Z, Huang Z, Li Y, Han N, Zhuang X, Peng H, Gao Q, Wang Q, Yang Lee BJ, Zhang H, Yang R, Bi Y, Xu ZZ (2022) Gut microbiome-targeted modulations regulate metabolic profiles and alleviate altitude-related cardiac hypertrophy in rats. Microbiol Spectr 10:e0105321. https://doi.org/10.1128/spectrum.01053-21

    Article  PubMed  Google Scholar 

  105. Dronkers TMG, Ouwehand AC, Rijkers GT (2020) Data on global analysis of clinical trials with probiotics. Data Brief 32:106269. https://doi.org/10.1016/j.dib.2020.106269

    Article  PubMed  PubMed Central  Google Scholar 

  106. Costanza AC, Moscavitch SD, Faria Neto HC, Mesquita ET (2015) Probiotic therapy with Saccharomyces boulardii for heart failure patients: a randomized, double-blind, placebo-controlled pilot trial. Int J Cardiol 179:348–350. https://doi.org/10.1016/j.ijcard.2014.11.034

    Article  PubMed  Google Scholar 

  107. Moludi J, Saiedi S, Ebrahimi B, Alizadeh M, Khajebishak Y, Ghadimi SS (2021) Probiotics supplementation on cardiac remodeling following myocardial infarction: a single-center double-blind clinical study. J Cardiovasc Transl Res 14:299–307. https://doi.org/10.1007/s12265-020-10052-1

    Article  PubMed  Google Scholar 

  108. Awoyemi A, Mayerhofer C, Felix AS, Hov JR, Moscavitch SD, Lappegård KT, Hovland A, Halvorsen S, Halvorsen B, Gregersen I, Svardal A, Berge RK, Hansen SH, Götz A, Holm K, Aukrust P, Åkra S, Seljeflot I, Solheim S, Lorenzo A, Gullestad L, Trøseid M, Broch K (2021) Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial. EBioMedicine 70:103511. https://doi.org/10.1016/j.ebiom.2021.103511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Matin SS, Shidfar F, Naderi N, Amin A, Hosseini-Baharanchi FS, Dehnad A (2022) The effect of synbiotic consumption on serum NTproBNP, hsCRP and blood pressure in patients with chronic heart failure: A randomized, triple-blind, controlled trial. Front Nutr 8:822498. https://doi.org/10.3389/fnut.2021.822498

    Article  CAS  Google Scholar 

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Funding

Studies cited from the authors’ laboratory were supported by a grant (MOP 62764) from the Canadian Institutes of Health Research. MK held a Canada Research Chair in Experimental Cardiology during the course of those studies.

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  1. Department of Pharmacology and Physiology, University of Western Ontario, London, ON, N6G 2X6, Canada

    Morris Karmazyn & Xiaohong Tracey Gan

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Karmazyn, M., Gan, X.T. Probiotics as potential treatments to reduce myocardial remodelling and heart failure via the gut-heart axis: State-of-the-art review. Mol Cell Biochem 478, 2539–2551 (2023). https://doi.org/10.1007/s11010-023-04683-6

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