The Role of Intestinal Flora and Its Metabolites in Heart Failure

References

• Heart Failure Group of Chinese Society of Cardiology of Chinese Medical A, Chinese Heart Failure Association of Chinese Medical Doctor A and Editorial Board of Chinese Journal of C. 中国心力衰竭诊断和治疗指南 [Chinese guidelines for the diagnosis and treatment of heart failure 2018]. Zhonghua Xin Xue Guan Bing Za Zhi. 2018;46(46):760–789. Chinese. doi:10.3760/cma.j.issn.0253-3758.2018.10.004
   PubMedGoogle Scholar
• Maggioni AP, Dahlström U, Filippatos G, et al. EURObservational research programme: regional differences and 1-year follow-up results of the heart failure pilot survey (ESC-HF pilot). Eur J Heart Fail. 2013;15:808–817. doi:10.1093/eurjhf/hft050
   PubMed Web of Science ®Google Scholar
• Yuzefpolskaya M, Bohn B, Nasiri M, et al. Gut microbiota, endotoxemia, inflammation, and oxidative stress in patients with heart failure, left ventricular assist device, and transplant. J Heart Lung Transpl. 2020;39(880–890):880–890. doi:10.1016/j.healun.2020.02.004
   PubMedGoogle Scholar
• Maddox J. Immunology made accessible. Nature. 1984;310:183. doi:10.1038/310183a0
   PubMed Web of Science ®Google Scholar
• Pasini E, Aquilani R, Testa C, et al. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016;4:220–227. doi:10.1016/j.jchf.2015.10.009
   PubMed Web of Science ®Google Scholar
• Krack A, Richartz BM, Gastmann A, et al. Studies on intragastric PCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure. Eur J Heart Fail. 2004;6:403–407. doi:10.1016/j.ejheart.2004.03.002
   PubMed Web of Science ®Google Scholar
• Sandek A, Bjarnason I, Volk H-D, et al. Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure. Int J Cardiol. 2012;157:80–85. doi:10.1016/j.ijcard.2010.12.016
   PubMed Web of Science ®Google Scholar
• Sandek A, Bauditz J, Swidsinski A, et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1561–1569. doi:10.1016/j.jacc.2007.07.016
   PubMed Web of Science ®Google Scholar
• 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;8:635. doi:10.1038/s41598-017-18756-2
   PubMed Web of Science ®Google Scholar
• Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14:e1002533. doi:10.1371/journal.pbio.1002533
   PubMed Web of Science ®Google Scholar
• Willyard C. New human gene tally reignites debate. Nature. 2018;558:354–355. doi:10.1038/d41586-018-05462-w
   PubMed Web of Science ®Google Scholar
• Tran TTT, Cousin FJ, Lynch DB, et al. Prebiotic supplementation in frail older people affects specific gut microbiota taxa but not global diversity. Microbiome. 2019;7(1):39. doi:10.1186/s40168-019-0654-1
   PubMedGoogle Scholar
• Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65. doi:10.1038/nature08821
   PubMed Web of Science ®Google Scholar
• Vijay A, Astbury S, Le Roy C, Spector TD, Valdes AM. The prebiotic effects of omega-3 fatty acid supplementation: a six-week randomised intervention trial. Gut Microb. 2021;13:1. doi:10.1080/19490976.2020.1863133
   PubMed Web of Science ®Google Scholar
• Desai MS, Seekatz AM, Koropatkin NM, et al. Gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167:1. doi:10.1016/j.cell.2016.10.043
   PubMed Web of Science ®Google Scholar
• Vallance HD, Koochin A, Branov J, Rosen-Heath A, Bosdet T, Wang Z. Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine. Mol Genet Metab Rep. 2018;15:130–133. doi:10.1016/j.ymgmr.2018.04.005
   PubMed Web of Science ®Google Scholar
• Koeth RA, Lam-Galvez BR, Kirsop J, et al. l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J Clin Invest. 2019;129:373–387. doi:10.1172/JCI94601
   PubMed Web of Science ®Google Scholar
• Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10:167–177. doi:10.1016/j.cmet.2009.08.001
   PubMed Web of Science ®Google Scholar
• Downes M, Verdecia MA, Roecker AJ, et al. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 2003;11:1079–1092. doi:10.1016/S1097-2765(03)00104-7
   PubMed Web of Science ®Google Scholar
• Gesper M, Nonnast ABH, Kumowski N, Stoehr R, Schuett K. Gut-derived metabolite indole-3-propionic acid modulates mitochondrial function in cardiomyocytes and alters cardiac function. Front Med. 2021;8:648259. doi:10.3389/fmed.2021.648259
   Web of Science ®Google Scholar
• Baxter NT, Lesniak NA, Sinani H. The glucoamylase inhibitor acarbose has a diet-dependent and reversible effect on the murine gut microbiome. mSphere. 2019;4:1.
   Google Scholar
• Di Iorio BR, Rocchetti MT, De Angelis M, Cosola C, Marzocco S, Di Micco L. Nutritional therapy modulates intestinal microbiota and reduces serum levels of total and free indoxyl sulfate and p-cresyl sulfate in chronic kidney disease (medika study). J Clin Med. 2019;8:1. doi:10.3390/jcm8091424
   Web of Science ®Google Scholar
• Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA. 2013;110(11):4410–4415. doi:10.1073/pnas.1215927110
   PubMed Web of Science ®Google Scholar
• Carrillo-Salinas FJ, Anastasiou M, Ngwenyama N, et al. Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner. Gut Microb. 2020;12:1–20. doi:10.1080/19490976.2020.1823801
   PubMed Web of Science ®Google Scholar
• Kelly CJ, Zheng L, Campbell EL, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial hif augments tissue barrier function. Cell Host Microbe. 2015;17:662–671. doi:10.1016/j.chom.2015.03.005
   PubMed Web of Science ®Google Scholar
• Vijay A, Astbury S, Panayiotis L, Marques FZ, Spector TD. Dietary interventions reduce traditional and novel cardiovascular risk markers by altering the gut microbiome and their metabolites. Front Cardiovasc Med. 2021;8:691564. doi:10.3389/fcvm.2021.691564
   PubMed Web of Science ®Google Scholar
• Tang TWH, Chen H-C, Chen C-Y, et al. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation. 2019;139:647–659. doi:10.1161/CIRCULATIONAHA.118.035235
   PubMed Web of Science ®Google Scholar
• Poll BG, Xu J, Jun S, et al. Acetate, a short-chain fatty acid, acutely lowers heart rate and cardiac contractility along with blood pressure. J Pharmacol Exp Ther. 2021;377:39–50. doi:10.1124/jpet.120.000187
   PubMed Web of Science ®Google Scholar
• Gupta N, Buffa JA, Roberts AB, et al. Targeted inhibition of gut microbial trimethylamine N-oxide production reduces renal tubulointerstitial fibrosis and functional impairment in a murine model of chronic kidney disease. Arterioscler Thromb Vasc Biol. 2020;40:1239–1255. doi:10.1161/ATVBAHA.120.314139
   PubMed Web of Science ®Google Scholar
• Koren O, Spor A, Felin J, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci USA. 2011;108(Suppl 1):4592–4598. doi:10.1073/pnas.1011383107
   PubMed Web of Science ®Google Scholar
• Yu H, Li L, Deng Y, et al. The relationship between the number of stenotic coronary arteries and the gut microbiome in coronary heart disease patients. Front Cell Infect Microbiol. 2022;12:903828. doi:10.3389/fcimb.2022.903828
   PubMed Web of Science ®Google Scholar
• Suzuki T, Yazaki Y, Voors AA, et al. Association with outcomes and response to treatment of trimethylamine N-oxide in heart failure: results from BIOSTAT-CHF. Eur J Heart Fail. 2019;21:877–886. doi:10.1002/ejhf.1338
   PubMed Web of Science ®Google Scholar
• Tang WHW, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM. 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. 2014;64:1908–1914. doi:10.1016/j.jacc.2014.02.617
   PubMed Web of Science ®Google Scholar
• Trøseid M, Ueland T, Hov JR, et al. Microbiota-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure. J Intern Med. 2015;277:717–726. doi:10.1111/joim.12328
   PubMed Web of Science ®Google Scholar
• Rhee EP, Clish CB, Ghorbani A, et al. A combined epidemiologic and metabolomic approach improves CKD prediction. J Am Soc Nephrol. 2013;24:1330–1338. doi:10.1681/ASN.2012101006
   PubMed Web of Science ®Google Scholar
• Tang WHW, Wang Z, Kennedy DJ, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116:448–455. doi:10.1161/CIRCRESAHA.116.305360
   PubMed Web of Science ®Google Scholar
• Zhang W, Miikeda A, Zuckerman J, et al. Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice. Sci Rep. 2021;11:518. doi:10.1038/s41598-020-80063-0
   PubMed Web of Science ®Google Scholar
• Wan Y, Yuan J, Li J, et al. Unconjugated and secondary bile acid profiles in response to higher-fat, lower-carbohydrate diet and associated with related gut microbiota: a 6-month randomized controlled-feeding trial. Clin Nutr. 2020;39:395–404. doi:10.1016/j.clnu.2019.02.037
   PubMed Web of Science ®Google Scholar
• Mayerhofer CCK, Ueland T, Broch K, et al. Increased secondary/primary bile acid ratio in chronic heart failure. J Card Fail. 2017;23:666–671. doi:10.1016/j.cardfail.2017.06.007
   PubMed Web of Science ®Google Scholar
• Bishop-Bailey D, Walsh DT, Warner TD. Expression and activation of the farnesoid X receptor in the vasculature. Proc Natl Acad Sci USA. 2004;101:3668–3673. doi:10.1073/pnas.0400046101
   PubMed Web of Science ®Google Scholar
• Xu M, Shen Y, Cen M, et al. Modulation of the gut microbiota-farnesoid X receptor axis improves deoxycholic acid-induced intestinal inflammation in mice. J Crohns Colitis. 2021;15:1197–1210. doi:10.1093/ecco-jcc/jjab003
   PubMedGoogle Scholar
• Ryan PM, Stanton C, Caplice NM. Bile acids at the cross-roads of gut microbiome-host cardiometabolic interactions. Diabetol Metab Syndr. 2017;9:102. doi:10.1186/s13098-017-0299-9
   PubMed Web of Science ®Google Scholar
• Xu J, Li X, Zhang F, et al. Integrated UPLC-Q/TOF-MS technique and MALDI-MS to study of the efficacy of yixinshu capsules against heart failure in a rat model. Front Pharmacol. 2019;6(10):1474. doi:10.3389/fphar.2019.01474
   Google Scholar
• Liu S, Pi Z, Liu Z, Song F, Liu S. Fecal metabolomics based on mass spectrometry to investigate the mechanism of qishen granules against isoproterenol-induced chronic heart failure in rats. J Sep Sci. 2020;43(23):4305–4313. doi:10.1002/jssc.202000622
   PubMed Web of Science ®Google Scholar
• von Haehling S, Schefold JC, Jankowska EA, et al. Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial. J Am Coll Cardiol. 2012;59(6):585–592. doi:10.1016/j.jacc.2011.10.880
   PubMed Web of Science ®Google Scholar
• Purcell NH, Tang G, Yu C, Mercurio F, DiDonato JA, Lin A. Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc Natl Acad Sci USA. 2001;98(12):6668–6673. doi:10.1073/pnas.111155798
   PubMed Web of Science ®Google Scholar
• Eblimit Z, Thevananther S, Karpen SJ, Taegtmeyer H, Moore DD, Adorini L. TGR5 activation induces cytoprotective changes in the heart and improves myocardial adaptability to physiologic, inotropic, and pressure-induced stress in mice. Cardiovasc Ther. 2018;36(5):e12462. doi:10.1111/1755-5922.12462
   PubMed Web of Science ®Google Scholar
• Aronov PA, Luo FJG, Plummer NS, Quan Z, Holmes S. Colonic contribution to uremic solutes. J Am Soc Nephrol. 2011;22:1769–1776. doi:10.1681/ASN.2010121220
   PubMed Web of Science ®Google Scholar
• Lekawanvijit S, Adrahtas A, Kelly DJ, Kompa AR, Wang BH, Krum H. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Eur Heart J. 2010;31(14):1771–1779. doi:10.1093/eurheartj/ehp574
   PubMed Web of Science ®Google Scholar
• Yisireyili M, Shimizu H, Saito S, Enomoto A, Nishijima F, Niwa T. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats. Life Sci. 2013;92(24–26):1180–1185. doi:10.1016/j.lfs.2013.05.008
   PubMed Web of Science ®Google Scholar
• Camacho O, Rosales MC, Shafi T, Fullman J, Plummer NS. Effect of a sustained difference in hemodialytic clearance on the plasma levels of p-cresol sulfate and indoxyl sulfate. Nephrol Dial Transplant. 2016;31:1335–1341. doi:10.1093/ndt/gfw100
   PubMed Web of Science ®Google Scholar
• Yang K, Xu X, Nie L, et al. Indoxyl sulfate induces oxidative stress and hypertrophy in cardiomyocytes by inhibiting the AMPK/UCP2 signaling pathway. Toxicol Lett. 2015;234:110–119. doi:10.1016/j.toxlet.2015.01.021
   PubMed Web of Science ®Google Scholar
• Yang K, Wang C, Nie L, et al. Klotho protects against indoxyl sulphate-induced myocardial hypertrophy. J Am Soc Nephrol. 2015;26:2434–2446. doi:10.1681/ASN.2014060543
   PubMed Web of Science ®Google Scholar
• Yazaki Y, Salzano A, Nelson CP, et al. Geographical location affects the levels and association of trimethylamine N-oxide with heart failure mortality in BIOSTAT-CHF: a post-hoc analysis. Eur J Heart Fail. 2019;21:1291–1294. doi:10.1002/ejhf.1550
   PubMed Web of Science ®Google Scholar
• Liyanage T, Ninomiya T, Wang A, et al. Effects of the Mediterranean diet on cardiovascular outcomes-a systematic review and meta-analysis. PLoS One. 2016;11:e0159252. doi:10.1371/journal.pone.0159252
   PubMed Web of Science ®Google Scholar
• Wang Z, Bergeron N, Levison BS, et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J. 2019;40:583–594. doi:10.1093/eurheartj/ehy799
   PubMed Web of Science ®Google Scholar
• Wang G, Kong B, Shuai W, Fu H, Jiang X, Huang H. 3,3-Dimethyl-1-butanol attenuates cardiac remodeling in pressure-overload-induced heart failure mice. J Nutr Biochem. 2020;78:108341. doi:10.1016/j.jnutbio.2020.108341
   PubMed Web of Science ®Google Scholar
• Conraads VM, Jorens PG, De Clerck LS, et al. Selective intestinal decontamination in advanced chronic heart failure: a pilot trial. Eur J Heart Fail. 2004;6:483–491. doi:10.1016/j.ejheart.2003.12.004
   PubMed Web of Science ®Google Scholar
• Kim ES, Yoon BH, Lee SM, et al. Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency. Exp Mol Med. 2022;54:103–114. doi:10.1038/s12276-022-00728-w
   PubMed Web of Science ®Google Scholar
• Hu X-F, Zhang W-Y, Wen Q, et al. Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition. Pharmacol Res. 2019;139:412–421.
   PubMed Web of Science ®Google Scholar
• DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-resistant bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019;381:2043–2050. doi:10.1056/NEJMoa1910437
   PubMed Web of Science ®Google Scholar
• Lam V, Su J, Koprowski S, et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26:1727–1735. doi:10.1096/fj.11-197921
   PubMed Web of Science ®Google Scholar
• Gan XT, Ettinger G, Huang CX, et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7:491–499.
   PubMed Web of Science ®Google Scholar
• Johnson LP, Walton GE, Psichas A, Frost GS, Gibson G, Barraclough T. Prebiotics modulate the effects of antibiotics on gut microbial diversity and functioning in vitro. Nutrients. 2015;7:4480–4497. doi:10.3390/nu7064480
   PubMed Web of Science ®Google Scholar
• Roberts AB, Gu X, Buffa JA, et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat Med. 2018;24:1407–1417. doi:10.1038/s41591-018-0128-1
   PubMed Web of Science ®Google Scholar
• Wang Z, Roberts AB, Buffa JA, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell. 2015;163:1585–1595. doi:10.1016/j.cell.2015.11.055
   PubMed Web of Science ®Google Scholar
• Asanuma H, Chung H, Ito S, et al. AST-120, an adsorbent of uremic toxins, improves the pathophysiology of heart failure in conscious dogs. Cardiovasc Drugs Ther. 2019;33:277–286. doi:10.1007/s10557-019-06875-z
   PubMed Web of Science ®Google Scholar
• Beale AL, O’Donnell JA, Nakai ME, et al. The gut microbiome of heart failure with preserved ejection fraction. J Am Heart Assoc. 2021;10:e020654. doi:10.1161/JAHA.120.020654
   PubMed Web of Science ®Google Scholar
• Li L, Zhong S-J, Hu S-Y, Cheng B, Qiu H, Hu Z-X. Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats. BMC Microbiol. 2021;21:141. doi:10.1186/s12866-021-02202-5
   PubMed Web of Science ®Google Scholar
• Kummen M, Mayerhofer C, Vestad B, et al. Gut microbiota signature in heart failure defined from profiling of 2 independent cohorts. J Am Coll Cardiol. 2018;71:1184–1186. doi:10.1016/j.jacc.2017.12.057
   PubMed Web of Science ®Google Scholar
• Deng F, Zhang L-Q, Wu H, et al. Propionate alleviates myocardial ischemia-reperfusion injury aggravated by Angiotensin II dependent on caveolin-1/ACE2 axis through GPR41. Int J Biol Sci. 2022;18:858–872. doi:10.7150/ijbs.67724
   PubMed Web of Science ®Google Scholar
• Tayyeb JZ, Popeijus HE, Mensink RP, Konings MCJM, Mokhtar FBA, Plat J. Short-chain fatty acids (except hexanoic acid) lower NF-kB transactivation, which rescues inflammation-induced decreased apolipoprotein A-I transcription in HepG2 cells. Int J Mol Sci. 2020;22:21. doi:10.3390/ijms22010021
   PubMedGoogle Scholar
• Oh TJ, Sul WJ, Oh HN, Lee Y-K, Lim HL, Choi SH. Butyrate attenuated fat gain through gut microbiota modulation in db/db mice following dapagliflozin treatment. Sci Rep. 2019;9:20300. doi:10.1038/s41598-019-56684-5
   PubMed Web of Science ®Google Scholar