Mechanistic Review on the Role of Gut Microbiota in the Pathology of
Cardiovascular Diseases

Iqra      Usman; Aamir      Anwar; Shivang      Shukla; Priya      Pathak
doi:10.2174/011871529X310857240607103028
Abstract

Cardiovascular diseases (CVDs), which stand as the primary contributors to illness and death on a global scale, include vital risk factors like hyperlipidemia, hypertension, diabetes, and smoking, to name a few. However, conventional cardiovascular risk factors offer only partial insight into the complexity of CVDs. Lately, a growing body of research has illuminated that the gut microbiome and its by-products are also of paramount importance in the initiation and progression of CVDs. The gastrointestinal tract houses trillions of microorganisms, commonly known as gut microbiota, that metabolize nutrients, yielding substances like trimethylamine-N-oxide (TMAO), bile acids (BAs), short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and so on. Strategies aimed at addressing these microbes and their correlated biological pathways have shown promise in the management and diagnosis of CVDs. This review offers a comprehensive examination of how the gut microbiota contributes to the pathogenesis of CVDs, particularly atherosclerosis, hypertension, heart failure (HF), and atrial fibrillation (AF), explores potential underlying mechanisms, and highlights emerging therapeutic prospects in this dynamic domain.
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Graphical Abstract

[1]
Wong, N.D.; Budoff, M.J.; Ferdinand, K.; Graham, I.M.; Michos, E.D.; Reddy, T.; Shapiro, M.D.; Toth, P.P. Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement. Am. J. Prev. Cardiol.,  2022, 10, 100335.
 [http://dx.doi.org/10.1016/j.ajpc.2022.100335] [PMID: 35342890]

[2]
Frąk, W.; Wojtasińska, A.; Lisińska, W.; Młynarska, E.; Franczyk, B.; Rysz, J. Pathophysiology of cardiovascular diseases: New insights into molecular mechanisms of atherosclerosis, arterial hypertension, and coronary artery disease. Biomedicines,  2022, 10(8), 1938.
 [http://dx.doi.org/10.3390/biomedicines10081938] [PMID: 36009488]

[3]
Francula-Zaninovic, S.; Nola, I.A. Management of measurable variable cardiovascular disease’ risk factors. Curr. Cardiol. Rev.,  2018, 14(3), 153-163.
 [http://dx.doi.org/10.2174/1573403X14666180222102312] [PMID: 29473518]

[4]
Mazmanian, S.K.; Liu, C.H.; Tzianabos, A.O.; Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell,  2005, 122(1), 107-118.
 [http://dx.doi.org/10.1016/j.cell.2005.05.007] [PMID: 16009137]

[5]
Desai, D.; Desai, A.; Jamil, A.; Csendes, D.; Gutlapalli, S.D.; Prakash, K.; Swarnakari, K.M.; Bai, M.; Manoharan, M.P.; Raja, R.; Khan, S. Re-defining the gut heart axis: A systematic review of the literature on the role of gut microbial dysbiosis in patients with heart failure. Cureus,  2023, 15(2), e34902.
 [http://dx.doi.org/10.7759/cureus.34902] [PMID: 36938237]

[6]
Robinson, C.J.; Bohannan, B.J.M.; Young, V.B. From structure to function: the ecology of host-associated microbial communities. Microbiol. Mol. Biol. Rev.,  2010, 74(3), 453-476.
 [http://dx.doi.org/10.1128/MMBR.00014-10] [PMID: 20805407]

[7]
Paster, B.J.; Boches, S.K.; Galvin, J.L.; Ericson, R.E.; Lau, C.N.; Levanos, V.A.; Sahasrabudhe, A.; Dewhirst, F.E. Bacterial diversity in human subgingival plaque. J. Bacteriol.,  2001, 183(12), 3770-3783.
 [http://dx.doi.org/10.1128/JB.183.12.3770-3783.2001] [PMID: 11371542]

[8]
Canfora, E.E.; Meex, R.C.R.; Venema, K.; Blaak, E.E. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat. Rev. Endocrinol.,  2019, 15(5), 261-273.
 [http://dx.doi.org/10.1038/s41574-019-0156-z] [PMID: 30670819]

[9]
Kim, S.; Jazwinski, S.M. The gut microbiota and healthy aging: A mini-review. Gerontology,  2018, 64(6), 513-520.
 [http://dx.doi.org/10.1159/000490615] [PMID: 30025401]

[10]
Kumar, D.; Mukherjee, S.S.; Chakraborty, R.; Roy, R.R.; Pandey, A.; Patra, S.; Dey, S. The emerging role of gut microbiota in cardiovascular diseases. Indian Heart J.,  2021, 73(3), 264-272.
 [http://dx.doi.org/10.1016/j.ihj.2021.04.008] [PMID: 34154741]

[11]
Eckburg, P. B.; Bik, E. M.; Bernstein, C. N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S. R.; Nelson, K. E.; Relman, D. A. Microbiology: Diversity of the human intestinal microbial flora. Science,  2005, 308(5728), 1635-1638.
 [http://dx.doi.org/10.1126/science.1110591]

[12]
Tang, W.H.W.; Kitai, T.; Hazen, S.L. Gut microbiota in cardiovascular health and disease. Circ. Res.,  2017, 120(7), 1183-1196.
 [http://dx.doi.org/10.1161/CIRCRESAHA.117.309715] [PMID: 28360349]

[13]
Byndloss, M.X.; Olsan, E.E.; Rivera-Chávez, F.; Tiffany, C.R.; Cevallos, S.A.; Lokken, K.L.; Torres, T.P.; Byndloss, A.J.; Faber, F.; Gao, Y.; Litvak, Y.; Lopez, C.A.; Xu, G.; Napoli, E.; Giulivi, C.; Tsolis, R.M.; Revzin, A.; Lebrilla, C.B.; Bäumler, A.J. Microbiota-activated PPAR-γ signaling inhibits dysbiotic enterobacteriaceae expansion. Science,  2017, 357(6351), 570-575.
 [http://dx.doi.org/10.1126/science.aam9949]

[14]
Gill, S.R.; Pop, M.; DeBoy, R. T.; Eckburg, P.B.; Turnbaugh, P.J.; Samuel, B.S.; Gordon, J.I.; Relman, D.A.; Fraser-Liggett, C.M.; Nelson, K.E. Metagenomic analysis of the human distal gut microbiome. Science,  2006, 312(5778), 1355-1359.
 [http://dx.doi.org/10.1126/science.1124234]

[15]
O’Hara, A.M.; Shanahan, F. The gut flora as a forgotten organ. EMBO Rep.,  2006, 7(7), 688-693.
 [http://dx.doi.org/10.1038/sj.embor.7400731] [PMID: 16819463]

[16]
Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; Mende, D.R.; Li, J.; Xu, J.; Li, S.; Li, D.; Cao, J.; Wang, B.; Liang, H.; Zheng, H.; Xie, Y.; Tap, J.; Lepage, P.; Bertalan, M.; Batto, J.M.; Hansen, T.; Le Paslier, D.; Linneberg, A.; Nielsen, H.B.; Pelletier, E.; Renault, P.; Sicheritz-Ponten, T.; Turner, K.; Zhu, H.; Yu, C.; Li, S.; Jian, M.; Zhou, Y.; Li, Y.; Zhang, X.; Li, S.; Qin, N.; Yang, H.; Wang, J.; Brunak, S.; Doré, J.; Guarner, F.; Kristiansen, K.; Pedersen, O.; Parkhill, J.; Weissenbach, J.; Bork, P.; Ehrlich, S.D.; Wang, J.; Antolin, M.; Artiguenave, F.; Blottiere, H.; Borruel, N.; Bruls, T.; Casellas, F.; Chervaux, C.; Cultrone, A.; Delorme, C.; Denariaz, G.; Dervyn, R.; Forte, M.; Friss, C.; Van De Guchte, M.; Guedon, E.; Haimet, F.; Jamet, A.; Juste, C.; Kaci, G.; Kleerebezem, M.; Knol, J.; Kristensen, M.; Layec, S.; Le Roux, K.; Leclerc, M.; Maguin, E.; Melo Minardi, R.; Oozeer, R.; Rescigno, M.; Sanchez, N.; Tims, S.; Torrejon, T.; Varela, E.; De Vos, W.; Winogradsky, Y.; Zoetendal, E. A human gut microbial gene catalogue established by metagenomic sequencing. Nature,  2010, 464(7285), 59-65.
 [http://dx.doi.org/10.1038/nature08821] [PMID: 20203603]

[17]
DeGruttola, A.K.; Low, D.; Mizoguchi, A.; Mizoguchi, E. Current understanding of dysbiosis in disease in human and animal models. Inflamm. Bowel Dis.,  2016, 22(5), 1137-1150.
 [http://dx.doi.org/10.1097/MIB.0000000000000750] [PMID: 27070911]

[18]
Thomas, R.M.; Jobin, C. Microbiota in pancreatic health and disease: The next frontier in microbiome research. Nat. Rev. Gastroenterol. Hepatol.,  2020, 17(1), 53-64.
 [http://dx.doi.org/10.1038/s41575-019-0242-7] [PMID: 31811279]

[19]
Wu, J.; Guo, Y.; Lu, X.; Huang, F.; Lv, F.; Wei, D.; Shang, A.; Yang, J.; Pan, Q.; Jiang, B.; Yu, J.; Cao, H.; Li, L. Th1/Th2 cells and associated cytokines in acute hepatitis E and related acute liver failure. J. Immunol. Res.,  2020, 2020, 1-8.
 [http://dx.doi.org/10.1155/2020/6027361] [PMID: 33294465]

[20]
Cui, D.; Tang, Y.; Jiang, Q.; Jiang, D.; Zhang, Y.; Lv, Y.; Xu, D.; Wu, J.; Xie, J.; Wen, C.; Lu, L. Follicular helper T cells in the immunopathogenesis of SARS-COV-2 infection. Front. Immunol.,  2021, 12, 731100.
 [http://dx.doi.org/10.3389/fimmu.2021.731100] [PMID: 34603308]

[21]
Yatsunenko, T.; Rey, F.E.; Manary, M.J.; Trehan, I.; Dominguez-Bello, M.G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R.N.; Anokhin, A.P.; Heath, A.C.; Warner, B.; Reeder, J.; Kuczynski, J.; Caporaso, J.G.; Lozupone, C.A.; Lauber, C.; Clemente, J.C.; Knights, D.; Knight, R.; Gordon, J.I. Human gut microbiome viewed across age and geography. Nature,  2012, 486(7402), 222-227.
 [http://dx.doi.org/10.1038/nature11053] [PMID: 22699611]

[22]
Hageman, J.H.J.; Keijer, J.; Dalsgaard, T.K.; Zeper, L.W.; Carrière, F.; Feitsma, A.L.; Nieuwenhuizen, A.G. Free fatty acid release from vegetable and bovine milk fat-based infant formulas and human milk during two-phase in vitro digestion. In: Food Func; , 2019; 10, pp. 2102-2113.
 [http://dx.doi.org/10.1039/C8FO01940A]

[23]
Panth, N.; Dias, C.B.; Wynne, K.; Singh, H.; Garg, M.L. Medium-chain fatty acids lower postprandial lipemia: A randomized crossover trial. Clin. Nutr.,  2020, 39(1), 90-96.
 [http://dx.doi.org/10.1016/j.clnu.2019.02.008] [PMID: 30824268]

[24]
Cummings, J.H.; Macfarlane, G.T. The control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol.,  1991, 70(6), 443-459.
 [http://dx.doi.org/10.1111/j.1365-2672.1991.tb02739.x] [PMID: 1938669]

[25]
Brown, J.M.; Hazen, S.L. Microbial modulation of cardiovascular disease. Nat. Rev. Microbiol.,  2018, 16(3), 171-181.
 [http://dx.doi.org/10.1038/nrmicro.2017.149] [PMID: 29307889]

[26]
Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA,  2014, 111(6), 2247-2252.
 [http://dx.doi.org/10.1073/pnas.1322269111] [PMID: 24390544]

[27]
Lu, Y.; Zhang, Y.; Zhao, X.; Shang, C.; Xiang, M.; Li, L.; Cui, X. Microbiota-derived short-chain fatty acids: Implications for cardiovascular and metabolic disease. Front. Cardiovasc. Med.,  2022, 9, 900381.
 [http://dx.doi.org/10.3389/fcvm.2022.900381] [PMID: 36035928]

[28]
Kummen, M.; Mayerhofer, C.C.K.; Vestad, B.; Broch, K.; Awoyemi, A.; Storm-Larsen, C.; Ueland, T.; Yndestad, A.; Hov, J.R.; Trøseid, M. Gut microbiota signature in heart failure defined from profiling of 2 independent cohorts. J. Am. Coll. Cardiol.,  2018, 71(10), 1184-1186.
 [http://dx.doi.org/10.1016/j.jacc.2017.12.057] [PMID: 29519360]

[29]
Trøseid, M.; Andersen, G.Ø.; Broch, K.; Hov, J.R. The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions. EBioMedicine,  2020, 52, 102649.
 [http://dx.doi.org/10.1016/j.ebiom.2020.102649] [PMID: 32062353]

[30]
Shakespear, M.R.; Halili, M.A.; Irvine, K.M.; Fairlie, D.P.; Sweet, M.J. Histone deacetylases as regulators of inflammation and immunity. Trends Immunol.,  2011, 32(7), 335-343.
 [http://dx.doi.org/10.1016/j.it.2011.04.001] [PMID: 21570914]

[31]
Cleophas, M.C.P.; Ratter, J.M.; Bekkering, S.; Quintin, J.; Schraa, K.; Stroes, E.S.; Netea, M.G.; Joosten, L.A.B. Effects of oral butyrate supplementation on inflammatory potential of circulating peripheral blood mononuclear cells in healthy and obese males. Sci. Rep.,  2019, 9(1), 775.
 [http://dx.doi.org/10.1038/s41598-018-37246-7] [PMID: 30692581]

[32]
Anshory, M.; Effendi, R.M.R.A.; Kalim, H.; Dwiyana, R.F.; Suwarsa, O.; Nijsten, T.E.C.; Nouwen, J.L.; Thio, H.B. Butyrate properties in immune-related diseases: Friend or foe? Fermentation,  2023, 9(3), 205.
 [http://dx.doi.org/10.3390/fermentation9030205]

[33]
Virendra, S.A.; Kumar, A.; Chawla, P.A.; Mamidi, N. Development of heterocyclic ppar ligands for potential therapeutic applications. Pharmaceutics,  2022, 14(10), 2139.
 [http://dx.doi.org/10.3390/pharmaceutics14102139] [PMID: 36297575]

[34]
Lin, Y.; Wang, Y.; Li, P. PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases. Front. Endocrinol.,  2022, 13, 1074911.
 [http://dx.doi.org/10.3389/fendo.2022.1074911] [PMID: 36589809]

[35]
Ansquer, J.C. The PPAR System in Diabetes In: Lipoproteins in Diabetes Mellitus; Springer, 2023. 
 [http://dx.doi.org/10.1007/978-3-031-26681-2_6]

[36]
Hafidi, M.E.; Buelna-Chontal, M.; Sánchez-Muñoz, F.; Carbó, R. Adipogenesis: A necessary but harmful strategy. Int. J. Mol. Sci.,  2019, 20(15), 3657.
 [http://dx.doi.org/10.3390/ijms20153657] [PMID: 31357412]

[37]
Korsten, S.G.P.J.; Vromans, H.; Garssen, J.; Willemsen, L.E.M. Butyrate protects barrier integrity and suppresses immune activation in a caco-2/pbmc co-culture model while hdac inhibition mimics butyrate in restoring cytokine-induced barrier disruption. Nutrients,  2023, 15(12), 2760.
 [http://dx.doi.org/10.3390/nu15122760] [PMID: 37375664]

[38]
Matheus, V.A.; Oliveira, R.B.; Maschio, D.A.; Tada, S.F.S.; Soares, G.M.; Mousovich-Neto, F.; Costa, R.G.; Mori, M.A.; Barbosa, H.C.L.; Collares-Buzato, C.B. Butyrate restores the fat/lean mass ratio balance and energy metabolism and reinforces the tight junction-mediated intestinal epithelial barrier in prediabetic mice independently of its anti-inflammatory and epigenetic actions. J. Nutr. Biochem.,  2023, 120, 109409.
 [http://dx.doi.org/10.1016/j.jnutbio.2023.109409] [PMID: 37364792]

[39]
Amiri, P.; Hosseini, S.A.; Roshanravan, N.; Saghafi-Asl, M.; Tootoonchian, M. The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial. Trials,  2023, 24(1), 489.
 [http://dx.doi.org/10.1186/s13063-022-06891-9] [PMID: 37528450]

[40]
Turchi, R.; Sciarretta, F.; Ceci, V.; Tiberi, M.; Audano, M.; Pedretti, S.; Panebianco, C.; Nesci, V.; Pazienza, V.; Ferri, A.; Carotti, S.; Chiurchiù, V.; Mitro, N.; Lettieri-Barbato, D.; Aquilano, K. Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich’s ataxia mouse model. iScience,  2023, 26(10), 107713.
 [http://dx.doi.org/10.1016/j.isci.2023.107713] [PMID: 37701569]

[41]
Lima, T.I.; Guimarães, D.; Sponton, C.H.; Bajgelman, M.C.; Palameta, S.; Toscaro, J.M.; Reis, O.; Silveira, L.R. Essential role of the PGC‐1α/PPARβ axis in Ucp3 gene induction. J. Physiol.,  2019, 597(16), 4277-4291.
 [http://dx.doi.org/10.1113/JP278006] [PMID: 31228206]

[42]
Hong, J.; Jia, Y.; Pan, S.; Jia, L.; Li, H.; Han, Z.; Cai, D.; Zhao, R. Butyrate alleviates high fat diet-induced obesity through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle of mice. Oncotarget,  2016, 7(35), 56071-56082.
 [http://dx.doi.org/10.18632/oncotarget.11267] [PMID: 27528227]

[43]
Fusco, R.; Siracusa, R.; Genovese, T.; Cuzzocrea, S.; Di Paola, R. Focus on the role of NLRP3 inflammasome in diseases. Int. J. Mol. Sci.,  2020, 21(12), 4223.
 [http://dx.doi.org/10.3390/ijms21124223] [PMID: 32545788]

[44]
Henao-Mejia, J.; Elinav, E.; Jin, C.; Hao, L.; Mehal, W.Z.; Strowig, T.; Thaiss, C.A.; Kau, A.L.; Eisenbarth, S.C.; Jurczak, M.J.; Camporez, J.P.; Shulman, G.I.; Gordon, J.I.; Hoffman, H.M.; Flavell, R.A. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature,  2012, 482(7384), 179-185.
 [http://dx.doi.org/10.1038/nature10809] [PMID: 22297845]

[45]
Mridha, A.R.; Wree, A.; Robertson, A.A.B.; Yeh, M.M.; Johnson, C.D.; Van Rooyen, D.M.; Haczeyni, F.; Teoh, N.C.H.; Savard, C.; Ioannou, G.N.; Masters, S.L.; Schroder, K.; Cooper, M.A.; Feldstein, A.E.; Farrell, G.C. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J. Hepatol.,  2017, 66(5), 1037-1046.
 [http://dx.doi.org/10.1016/j.jhep.2017.01.022] [PMID: 28167322]

[46]
Zambetti, L.P.; Mortellaro, A. NLRPS, microbiota, and gut homeostasis: Unravelling the connection. J. Pathol.,  2014, 233(4), 321-330.
 [http://dx.doi.org/10.1002/path.4357] [PMID: 24740681]

[47]
Wen, H.; Ting, J.P.Y.; O’Neill, L.A.J. A role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation? Nat. Immunol.,  2012, 13(4), 352-357.
 [http://dx.doi.org/10.1038/ni.2228] [PMID: 22430788]

[48]
Inserra, A.; Rogers, G.B.; Licinio, J.; Wong, M.L. The microbiota‐inflammasome hypothesis of major depression. BioEssays,  2018, 40(9), 1800027.
 [http://dx.doi.org/10.1002/bies.201800027] [PMID: 30004130]

[49]
Poznyak, A.V.; Melnichenko, A.A.; Wetzker, R.; Gerasimova, E.V.; Orekhov, A.N. NLPR3 inflammasomes and their significance for atherosclerosis. Biomedicines,  2020, 8(7), 205.
 [http://dx.doi.org/10.3390/biomedicines8070205] [PMID: 32664349]

[50]
Liu, H.; Zhuang, J.; Tang, P.; Li, J.; Xiong, X.; Deng, H. The role of the gut microbiota in coronary heart disease. Curr. Atheroscler. Rep.,  2020, 22(12), 77.
 [http://dx.doi.org/10.1007/s11883-020-00892-2] [PMID: 33063240]

[51]
Feng, Y.; Wang, Y.; Wang, P.; Huang, Y.; Wang, F. Short-chain fatty acids manifest stimulative and protective effects on intestinal barrier function through the inhibition of nlrp3 inflammasome and autophagy. Cell. Physiol. Biochem.,  2018, 49(1), 190-205.
 [http://dx.doi.org/10.1159/000492853] [PMID: 30138914]

[52]
Yuan, X.; Wang, L.; Bhat, O.M.; Lohner, H.; Li, P.L. Differential effects of short chain fatty acids on endothelial Nlrp3 inflammasome activation and neointima formation: Antioxidant action of butyrate. Redox Biol.,  2018, 16, 21-31.
 [http://dx.doi.org/10.1016/j.redox.2018.02.007] [PMID: 29475132]

[53]
Xu, M.; Jiang, Z.; Wang, C.; Li, N.; Bo, L.; Zha, Y.; Bian, J.; Zhang, Y.; Deng, X. Acetate attenuates inflammasome activation through GPR43-mediated Ca2+-dependent NLRP3 ubiquitination. Exp. Mol. Med.,  2019, 51(7), 1-13.
 [http://dx.doi.org/10.1038/s12276-019-0276-5] [PMID: 31337751]

[54]
Chen, Y.; Xu, C.; Huang, R.; Song, J.; Li, D.; Xia, M. Butyrate from pectin fermentation inhibits intestinal cholesterol absorption and attenuates atherosclerosis in apolipoprotein E-deficient mice. J. Nutr. Biochem.,  2018, 56, 175-182.
 [http://dx.doi.org/10.1016/j.jnutbio.2018.02.011] [PMID: 29574331]

[55]
Aguilar, E.C.; Leonel, A.J.; Teixeira, L.G.; Silva, A.R.; Silva, J.F.; Pelaez, J.M.N.; Capettini, L.S.A.; Lemos, V.S.; Santos, R.A.S.; Alvarez-Leite, J.I. Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation. Nutr. Metab. Cardiovasc. Dis.,  2014, 24(6), 606-613.
 [http://dx.doi.org/10.1016/j.numecd.2014.01.002] [PMID: 24602606]

[56]
Li, H.; Gao, Z.; Zhang, J.; Ye, X.; Xu, A.; Ye, J.; Jia, W. Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3. Diabetes,  2012, 61(4), 797-806.
 [http://dx.doi.org/10.2337/db11-0846] [PMID: 22338096]

[57]
Li, M.; van Esch, B.C.A.M.; Henricks, P.A.J.; Garssen, J.; Folkerts, G. Time and concentration dependent effects of short chain fatty acids on lipopolysaccharide- or tumor necrosis factor α-induced endothelial activation. Front. Pharmacol.,  2018, 9(MAR), 233.
 [http://dx.doi.org/10.3389/fphar.2018.00233] [PMID: 29615908]

[58]
Finn, A.V.; Nakano, M.; Polavarapu, R.; Karmali, V.; Saeed, O.; Zhao, X.; Yazdani, S.; Otsuka, F.; Davis, T.; Habib, A.; Narula, J.; Kolodgie, F.D.; Virmani, R. Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J. Am. Coll. Cardiol.,  2012, 59(2), 166-177.
 [http://dx.doi.org/10.1016/j.jacc.2011.10.852] [PMID: 22154776]

[59]
Tayyeb, J.Z.; Popeijus, H.E.; Mensink, R.P.; Konings, M.C.J.M.; Mokhtar, F.B.A.; 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, 21(14), 5088.
 [http://dx.doi.org/10.3390/ijms21145088] [PMID: 32708494]

[60]
Kasahara, K.; Krautkramer, K.A.; Org, E.; Romano, K.A.; Kerby, R.L.; Vivas, E.I.; Mehrabian, M.; Denu, J.M.; Bäckhed, F.; Lusis, A.J.; Rey, F.E. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat. Microbiol.,  2018, 3(12), 1461-1471.
 [http://dx.doi.org/10.1038/s41564-018-0272-x] [PMID: 30397344]

[61]
Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J.R.; Pfeffer, K.; Coffer, P.J.; Rudensky, A.Y. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature,  2013, 504(7480), 451-455.
 [http://dx.doi.org/10.1038/nature12726] [PMID: 24226773]

[62]
Aguilar, E.C.; Santos, L.C.; Leonel, A.J.; de Oliveira, J.S.; Santos, E.A.; Navia-Pelaez, J.M.; da Silva, J.F.; Mendes, B.P.; Capettini, L.S.A.; Teixeira, L.G.; Lemos, V.S.; Alvarez-Leite, J.I. Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells. J. Nutr. Biochem.,  2016, 34, 99-105.
 [http://dx.doi.org/10.1016/j.jnutbio.2016.05.002] [PMID: 27261536]

[63]
Eblimit, Z.; Thevananther, S.; Karpen, S.J.; Taegtmeyer, H.; Moore, D.D.; Adorini, L.; Penny, D.J.; Desai, M.S. TGR 5 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.
 [http://dx.doi.org/10.1111/1755-5922.12462] [PMID: 30070769]

[64]
Tang, T.T.; Yuan, J.; Zhu, Z.F.; Zhang, W.C.; Xiao, H.; Xia, N.; Yan, X.X.; Nie, S.F.; Liu, J.; Zhou, S.F.; Li, J.J.; Yao, R.; Liao, M.Y.; Tu, X.; Liao, Y.H.; Cheng, X.; Regulatory, T. Regulatory T cells ameliorate cardiac remodeling after myocardial infarction. Basic Res. Cardiol.,  2012, 107(1), 232.
 [http://dx.doi.org/10.1007/s00395-011-0232-6] [PMID: 22189560]

[65]
Nagatomo, Y.; Tang, W.H.W. Intersections between microbiome and heart failure: Revisiting the gut hypothesis. J. Card. Fail.,  2015, 21(12), 973-980.
 [http://dx.doi.org/10.1016/j.cardfail.2015.09.017] [PMID: 26435097]

[66]
Tang, T.W.H.; Chen, H.C.; Chen, C.Y.; Yen, C.Y.T.; Lin, C.J.; Prajnamitra, R.P.; Chen, L.L.; Ruan, S.C.; Lin, J.H.; Lin, P.J.; Lu, H.H.; Kuo, C.W.; Chang, C.M.; Hall, A.D.; Vivas, E.I.; Shui, J.W.; Chen, P.; Hacker, T.A.; Rey, F.E.; Kamp, T.J.; Hsieh, P.C.H. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation,  2019, 139(5), 647-659.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035235] [PMID: 30586712]

[67]
Beale, A.L.; O’Donnell, J.A.; Nakai, M.E.; Nanayakkara, S.; Vizi, D.; Carter, K.; Dean, E.; Ribeiro, R.V.; Yiallourou, S.; Carrington, M.J.; Marques, F.Z.; Kaye, D.M. The gut microbiome of heart failure with preserved ejection fraction. J. Am. Heart Assoc.,  2021, 10(13), e020654.
 [http://dx.doi.org/10.1161/JAHA.120.020654] [PMID: 34212778]

[68]
Zhou, M.; Li, D.; Xie, K.; Xu, L.; Kong, B.; Wang, X.; Tang, Y.; Liu, Y.; Huang, H. The short-chain fatty acid propionate improved ventricular electrical remodeling in a rat model with myocardial infarction. Food Funct.,  2021, 12(24), 12580-12593.
 [http://dx.doi.org/10.1039/D1FO02040D] [PMID: 34813637]

[69]
Carley, A.N.; Maurya, S.K.; Fasano, M.; Wang, Y.; Selzman, C.H.; Drakos, S.G.; Lewandowski, E.D. Short-chain fatty acids outpace ketone oxidation in the failing heart. Circulation,  2021, 143(18), 1797-1808.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052671] [PMID: 33601938]

[70]
Muralitharan, R.R.; Jama, H.A.; Xie, L.; Peh, A.; Snelson, M.; Marques, F.Z. Microbial peer pressure. Hypertension,  2020, 76(6), 1674-1687.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14473] [PMID: 33012206]

[71]
Zhang, J.; Zuo, K.; Fang, C.; Yin, X.; Liu, X.; Zhong, J.; Li, K.; Li, J.; Xu, L.; Yang, X. Altered synthesis of genes associated with short-chain fatty acids in the gut of patients with atrial fibrillation. BMC Genom.,  2021, 22(1), 634.
 [http://dx.doi.org/10.1186/s12864-021-07944-0] [PMID: 34465304]

[72]
Nie, K.; Ma, K.; Luo, W.; Shen, Z.; Yang, Z.; Xiao, M.; Tong, T.; Yang, Y.; Wang, X. Roseburia intestinalis: A beneficial gut organism from the discoveries in genus and species. Front. Cell. Infect. Microbiol.,  2021, 11, 757718.
 [http://dx.doi.org/10.3389/fcimb.2021.757718] [PMID: 34881193]

[73]
Brown, A.J.; Goldsworthy, S.M.; Barnes, A.A.; Eilert, M.M.; Tcheang, L.; Daniels, D.; Muir, A.I.; Wigglesworth, M.J.; Kinghorn, I.; Fraser, N.J.; Pike, N.B.; Strum, J.C.; Steplewski, K.M.; Murdock, P.R.; Holder, J.C.; Marshall, F.H.; Szekeres, P.G.; Wilson, S.; Ignar, D.M.; Foord, S.M.; Wise, A.; Dowell, S.J. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem.,  2003, 278(13), 11312-11319.
 [http://dx.doi.org/10.1074/jbc.M211609200] [PMID: 12496283]

[74]
Gruppen, E.G.; Garcia, E.; Connelly, M.A.; Jeyarajah, E.J.; Otvos, J.D.; Bakker, S.J.L.; Dullaart, R.P.F. TMAO is associated with mortality: Impact of modestly impaired renal function. Sci. Rep.,  2017, 7(1), 13781.
 [http://dx.doi.org/10.1038/s41598-017-13739-9] [PMID: 29061990]

[75]
Roberts, A.B.; Gu, X.; Buffa, J.A.; Hurd, A.G.; Wang, Z.; Zhu, W.; Gupta, N.; Skye, S.M.; Cody, D.B.; Levison, B.S.; Barrington, W.T.; Russell, M.W.; Reed, J.M.; Duzan, A.; Lang, J.M.; Fu, X.; Li, L.; Myers, A.J.; Rachakonda, S.; DiDonato, J.A.; Brown, J.M.; Gogonea, V.; Lusis, A.J.; Garcia-Garcia, J.C.; Hazen, S.L. Development of a gut microbe–targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med.,  2018, 24(9), 1407-1417.
 [http://dx.doi.org/10.1038/s41591-018-0128-1] [PMID: 30082863]

[76]
Yang, S.; Li, X.; Yang, F.; Zhao, R.; Pan, X.; Liang, J.; Tian, L.; Li, X.; Liu, L.; Xing, Y.; Wu, M. Gut microbiota-dependent marker TMAO in promoting cardiovascular disease: Inflammation mechanism, clinical prognostic, and potential as a therapeutic target. Front. Pharmacol.,  2019, 10, 1360.
 [http://dx.doi.org/10.3389/fphar.2019.01360] [PMID: 31803054]

[77]
Romano, K.A.; Vivas, E.I.; Amador-Noguez, D.; Rey, F.E. Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite trimethylamine-N-oxide. MBio,  2015, 6(2), e02481-14.
 [http://dx.doi.org/10.1128/mBio.02481-14] [PMID: 25784704]

[78]
Borges, N.A.; Stenvinkel, P.; Bergman, P.; Qureshi, A.R.; Lindholm, B.; Moraes, C.; Stockler-Pinto, M.B.; Mafra, D. Effects of probiotic supplementation on trimethylamine-n-oxide plasma levels in hemodialysis patients: A pilot study. Probiot. Antimicrob. Proteins,  2019, 11(2), 648-654.
 [http://dx.doi.org/10.1007/s12602-018-9411-1] [PMID: 29651635]

[79]
Koeth, R.A.; Lam-Galvez, B.R.; Kirsop, J.; Wang, Z.; Levison, B.S.; Gu, X.; Copeland, M.F.; Bartlett, D.; Cody, D.B.; Dai, H.J.; Culley, M.K.; Li, X.S.; Fu, X.; Wu, Y.; Li, L.; DiDonato, J.A.; Tang, W.H.W.; Garcia-Garcia, J.C.; Hazen, S.L. l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J. Clin. Invest.,  2018, 129(1), 373-387.
 [http://dx.doi.org/10.1172/JCI94601] [PMID: 30530985]

[80]
Zeisel, S.H.; Warrier, M. Trimethylamine n -oxide, the microbiome, and heart and kidney disease. Annu. Rev. Nutr.,  2017, 37(1), 157-181.
 [http://dx.doi.org/10.1146/annurev-nutr-071816-064732] [PMID: 28715991]

[81]
Romero, E.; Gómez Castellanos, J.R.; Gadda, G.; Fraaije, M.W.; Mattevi, A. Same substrate, many reactions: Oxygen activation in flavoenzymes. Chem. Rev.,  2018, 118(4), 1742-1769.
 [http://dx.doi.org/10.1021/acs.chemrev.7b00650] [PMID: 29323892]

[82]
Reis, R.A.G.; Li, H.; Johnson, M.; Sobrado, P. New frontiers in flavin-dependent monooxygenases. Arch. Biochem. Biophys.,  2021, 699, 108765.
 [http://dx.doi.org/10.1016/j.abb.2021.108765] [PMID: 33460580]

[83]
Velasquez, M.; Ramezani, A.; Manal, A.; Raj, D. Trimethylamine N-oxide: The good, the bad and the unknown. Toxins,  2016, 8(11), 326.
 [http://dx.doi.org/10.3390/toxins8110326] [PMID: 27834801]

[84]
Ding, L.; Chang, M.; Guo, Y.; Zhang, L.; Xue, C.; Yanagita, T.; Zhang, T.; Wang, Y. Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism. Lipids Health Dis.,  2018, 17(1), 286.
 [http://dx.doi.org/10.1186/s12944-018-0939-6] [PMID: 30567573]

[85]
Tousoulis, D.; Oikonomou, E.; Economou, E.K.; Crea, F.; Kaski, J.C. Inflammatory cytokines in atherosclerosis: Current therapeutic approaches. Eur. Heart J.,  2016, 37(22), 1723-1732.
 [http://dx.doi.org/10.1093/eurheartj/ehv759] [PMID: 26843277]

[86]
Zhang, X.; Gérard, P. Diet-gut microbiota interactions on cardiovascular disease. Comput. Struct. Biotechnol. J.,  2022, 20, 1528-1540.
 [http://dx.doi.org/10.1016/j.csbj.2022.03.028] [PMID: 35422966]

[87]
Zheng, Y.; He, J.Q. Pathogenic mechanisms of trimethylamine n-oxide-induced atherosclerosis and cardiomyopathy. Curr. Vasc. Pharmacol.,  2022, 20(1), 29-36.
 [http://dx.doi.org/10.2174/1570161119666210812152802] [PMID: 34387163]

[88]
Koeth, R.A.; Wang, Z.; Levison, B.S.; Buffa, J.A.; Org, E.; Sheehy, B.T.; Britt, E.B.; Fu, X.; Wu, Y.; Li, L.; Smith, J.D.; DiDonato, J.A.; Chen, J.; Li, H.; Wu, G.D.; Lewis, J.D.; Warrier, M.; Brown, J.M.; Krauss, R.M.; Tang, W.H.W.; Bushman, F.D.; Lusis, A.J.; Hazen, S.L. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med.,  2013, 19(5), 576-585.
 [http://dx.doi.org/10.1038/nm.3145] [PMID: 23563705]

[89]
Wang, Z.; Klipfell, E.; Bennett, B.J.; Koeth, R.; Levison, B.S.; DuGar, B.; Feldstein, A.E.; Britt, E.B.; Fu, X.; Chung, Y.M.; Wu, Y.; Schauer, P.; Smith, J.D.; Allayee, H.; Tang, W.H.W.; DiDonato, J.A.; Lusis, A.J.; Hazen, S.L. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature,  2011, 472(7341), 57-63.
 [http://dx.doi.org/10.1038/nature09922] [PMID: 21475195]

[90]
Kubitz, R.; Dröge, C.; Stindt, J.; Weissenberger, K.; Häussinger, D. The bile salt export pump (BSEP) in health and disease. Clin. Res. Hepatol. Gastroenterol.,  2012, 36(6), 536-553.
 [http://dx.doi.org/10.1016/j.clinre.2012.06.006] [PMID: 22795478]

[91]
Canyelles, M.; Tondo, M.; Cedó, L.; Farràs, M.; Escolà-Gil, J.; Blanco-Vaca, F. Trimethylamine n-oxide: A link among diet, gut microbiota, gene regulation of liver and intestine cholesterol homeostasis and hdl function. Int. J. Mol. Sci.,  2018, 19(10), 3228.
 [http://dx.doi.org/10.3390/ijms19103228] [PMID: 30347638]

[92]
Liu, X.; Shao, Y.; Tu, J.; Sun, J.; Li, L.; Tao, J.; Chen, J. Trimethylamine-N-oxide-stimulated hepatocyte-derived exosomes promote inflammation and endothelial dysfunction through nuclear factor-kappa B signaling. Ann. Transl. Med.,  2021, 9(22), 1670.
 [http://dx.doi.org/10.21037/atm-21-5043] [PMID: 34988179]

[93]
Zhou, S.; Xue, J.; Shan, J.; Hong, Y.; Zhu, W.; Nie, Z.; Zhang, Y.; Ji, N.; Luo, X.; Zhang, T.; Ma, W. Gut-flora-dependent metabolite trimethylamine-n-oxide promotes atherosclerosis-associated inflammation responses by indirect ros stimulation and signaling involving AMPK and SIRT1. Nutrients,  2022, 14(16), 3338.
 [http://dx.doi.org/10.3390/nu14163338] [PMID: 36014845]

[94]
Sun, X.; Jiao, X.; Ma, Y.; Liu, Y.; Zhang, L.; He, Y.; Chen, Y. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem. Biophys. Res. Commun.,  2016, 481(1-2), 63-70.
 [http://dx.doi.org/10.1016/j.bbrc.2016.11.017] [PMID: 27833015]

[95]
Li, T.; Chen, Y.; Gua, C.; Li, X. Elevated circulating trimethylamine n-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Front. Physiol.,  2017, 8(MAY), 350.
 [http://dx.doi.org/10.3389/fphys.2017.00350] [PMID: 28611682]

[96]
Lee, J.; Lee, S.; Zhang, H.; Hill, M.A.; Zhang, C.; Park, Y. Interaction of IL-6 and TNF-α contributes to endothelial dysfunction in type 2 diabetic mouse hearts. PLoS One,  2017, 12(11), e0187189.
 [http://dx.doi.org/10.1371/journal.pone.0187189] [PMID: 29095915]

[97]
Raggi, P.; Genest, J.; Giles, J.T.; Rayner, K.J.; Dwivedi, G.; Beanlands, R.S.; Gupta, M. Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis,  2018, 276, 98-108.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2018.07.014] [PMID: 30055326]

[98]
Singh, G.B.; Zhang, Y.; Boini, K.M.; Koka, S. High mobility group box 1 mediates TMAO-induced endothelial dysfunction. Int. J. Mol. Sci.,  2019, 20(14), 3570.
 [http://dx.doi.org/10.3390/ijms20143570] [PMID: 31336567]

[99]
Yang, W.S.; Han, N.J.; Kim, J.J.; Lee, M.J.; Park, S.K. TNF-α activates high-mobility group box 1 - toll-like receptor 4 signaling pathway in human aortic endothelial cells. Cell. Physiol. Biochem.,  2016, 38(6), 2139-2151.
 [http://dx.doi.org/10.1159/000445570] [PMID: 27184952]

[100]
Miteva, K.; Madonna, R.; De Caterina, R.; Van Linthout, S. Innate and adaptive immunity in atherosclerosis. Vascul. Pharmacol.,  2018, 107, 67-77.
 [http://dx.doi.org/10.1016/j.vph.2018.04.006] [PMID: 29684642]

[101]
Ma, G.; Pan, B.; Chen, Y.; Guo, C.; Zhao, M.; Zheng, L.; Chen, B. Trimethylamine N-oxide in atherogenesis: Impairing endothelial self-repair capacity and enhancing monocyte adhesion. Biosci. Rep.,  2017, 37(2), BSR20160244.
 [http://dx.doi.org/10.1042/BSR20160244] [PMID: 28153917]

[102]
Seldin, M.M.; Meng, Y.; Qi, H.; Zhu, W.; Wang, Z.; Hazen, S.L.; Lusis, A.J.; Shih, D.M. Trimethylamine n-oxide promotes vascular inflammation through signaling of mitogen-activated protein kinase and nuclear factor-κB. J. Am. Heart Assoc.,  2016, 5(2), e002767.
 [http://dx.doi.org/10.1161/JAHA.115.002767] [PMID: 26903003]

[103]
Pan, B.; Ma, Y.; Ren, H.; He, Y.; Wang, Y.; Lv, X.; Liu, D.; Ji, L.; Yu, B.; Wang, Y.; Chen, Y.E.; Pennathur, S.; Smith, J.D.; Liu, G.; Zheng, L. Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression. PLoS One,  2012, 7(11), e48530.
 [http://dx.doi.org/10.1371/journal.pone.0048530] [PMID: 23133640]

[104]
Zhu, W.; Buffa, J.A.; Wang, Z.; Warrier, M.; Schugar, R.; Shih, D.M.; Gupta, N.; Gregory, J.C.; Org, E.; Fu, X.; Li, L.; DiDonato, J.A.; Lusis, A.J.; Brown, J.M.; Hazen, S.L. Flavin monooxygenase 3, the host hepatic enzyme in the metaorganismal trimethylamine N‐oxide‐generating pathway, modulates platelet responsiveness and thrombosis risk. J. Thromb. Haemost.,  2018, 16(9), 1857-1872.
 [http://dx.doi.org/10.1111/jth.14234] [PMID: 29981269]

[105]
Zhou, X.; Chen, M.; Zeng, X.; Yang, J.; Deng, H.; Yi, L.; Mi, M. Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells. Cell Death Dis.,  2014, 5(12), e1576.
 [http://dx.doi.org/10.1038/cddis.2014.530] [PMID: 25522270]

[106]
Zhu, W.; Gregory, J.C.; Org, E.; Buffa, J.A.; Gupta, N.; Wang, Z.; Li, L.; Fu, X.; Wu, Y.; Mehrabian, M.; Sartor, R.B.; McIntyre, T.M.; Silverstein, R.L.; Tang, W.H.W.; DiDonato, J.A.; Brown, J.M.; Lusis, A.J.; Hazen, S.L. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell,  2016, 165(1), 111-124.
 [http://dx.doi.org/10.1016/j.cell.2016.02.011] [PMID: 26972052]

[107]
Chen, M.; Zhu, X.; Ran, L.; Lang, H.; Yi, L.; Mi, M. Trimethylamine-n-oxide induces vascular inflammation by activating the nlrp3 inflammasome through the sirt3-sod2-mtros signaling pathway. J. Am. Heart Assoc.,  2017, 6(9), e006347.
 [http://dx.doi.org/10.1161/JAHA.117.006347] [PMID: 28871042]

[108]
Ray, P.D.; Huang, B.W.; Tsuji, Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell. Signal.,  2012, 24(5), 981-990.
 [http://dx.doi.org/10.1016/j.cellsig.2012.01.008] [PMID: 22286106]

[109]
Chou, R.H.; Chen, C.Y.; Chen, I.C.; Huang, H.L.; Lu, Y.W.; Kuo, C.S.; Chang, C.C.; Huang, P.H.; Chen, J.W.; Lin, S.J. Trimethylamine n-oxide, circulating endothelial progenitor cells, and endothelial function in patients with stable angina. Sci. Rep.,  2019, 9(1), 4249.
 [http://dx.doi.org/10.1038/s41598-019-40638-y] [PMID: 30862856]

[110]
Michowitz, Y.; Goldstein, E.; Wexler, D.; Sheps, D.; Keren, G.; George, J. Circulating endothelial progenitor cells and clinical outcome in patients with congestive heart failure. Heart,  2007, 93(9), 1046-1050.
 [http://dx.doi.org/10.1136/hrt.2006.102657] [PMID: 17277352]

[111]
Yang, Z.; Wang, Q.; Liu, Y.; Wang, L.; Ge, Z.; Li, Z.; Feng, S.; Wu, C. Gut microbiota and hypertension: Association, mechanisms and treatment. Clin. Exp. Hypertens.,  2023, 45(1), 2195135.
 [http://dx.doi.org/10.1080/10641963.2023.2195135] [PMID: 36994745]

[112]
Duttaroy, A.K. Role of gut microbiota and their metabolites on atherosclerosis, hypertension and human blood platelet function: A Review. Nutrients,  2021, 13(1), 144.
 [http://dx.doi.org/10.3390/nu13010144] [PMID: 33401598]

[113]
Ge, X.; Zheng, L.; Zhuang, R.; Yu, P.; Xu, Z.; Liu, G.; Xi, X.; Zhou, X.; Fan, H. The gut microbial metabolite trimethylamine n-oxide and hypertension risk: A systematic review and dose–response meta-analysis. Adv. Nutr.,  2020, 11(1), 66-76.
 [http://dx.doi.org/10.1093/advances/nmz064] [PMID: 31269204]

[114]
Jiang, S.; Shui, Y.; Cui, Y.; Tang, C.; Wang, X.; Qiu, X.; Hu, W.; Fei, L.; Li, Y.; Zhang, S.; Zhao, L.; Xu, N.; Dong, F.; Ren, X.; Liu, R.; Persson, P.B.; Patzak, A.; Lai, E.Y.; Wei, Q.; Zheng, Z. Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II–induced hypertension. Redox Biol.,  2021, 46, 102115.
 [http://dx.doi.org/10.1016/j.redox.2021.102115] [PMID: 34474396]

[115]
Liu, M.; Han, Q.; Yang, J. Trimethylamine-N-oxide (TMAO) increased aquaporin-2 expression in spontaneously hypertensive rats. Clin. Exp. Hypertens.,  2019, 41(4), 312-322.
 [http://dx.doi.org/10.1080/10641963.2018.1481420] [PMID: 29985655]

[116]
Jia, Q.; Li, H.; Zhou, H.; Zhang, X.; Zhang, A.; Xie, Y.; Li, Y.; Lv, S.; Zhang, J. Role and effective therapeutic target of gut microbiota in heart failure. Cardiovasc. Ther.,  2019, 2019, 1-10.
 [http://dx.doi.org/10.1155/2019/5164298] [PMID: 31819762]

[117]
Suzuki, T.; Yazaki, Y.; Voors, A.A.; Jones, D.J.L.; Chan, D.C.S.; Anker, S.D.; Cleland, J.G.; Dickstein, K.; Filippatos, G.; Hillege, H.L.; Lang, C.C.; Ponikowski, P.; Samani, N.J.; van Veldhuisen, D.J.; Zannad, F.; Zwinderman, A.H.; Metra, M.; Ng, L.L. Association with outcomes and response to treatment of trimethylamine N-oxide in heart failure: results from BIOSTAT-CHF. Eur. J. Heart Fail.,  2019, 21(7), 877-886.
 [http://dx.doi.org/10.1002/ejhf.1338] [PMID: 30370976]

[118]
Drapala, A.; Szudzik, M.; Chabowski, D.; Mogilnicka, I.; Jaworska, K.; Kraszewska, K.; Samborowska, E.; Ufnal, M. Heart failure disturbs gut–blood barrier and increases plasma trimethylamine, a toxic bacterial metabolite. Int. J. Mol. Sci.,  2020, 21(17), 6161.
 [http://dx.doi.org/10.3390/ijms21176161] [PMID: 32859047]

[119]
Organ, C.L.; Li, Z.; Sharp, T.E., III; Polhemus, D.J.; Gupta, N.; Goodchild, T.T.; Tang, W.H.W.; Hazen, S.L.; Lefer, D.J. Nonlethal inhibition of gut microbial trimethylamine n‐oxide production improves cardiac function and remodeling in a murine model of heart failure. J. Am. Heart Assoc.,  2020, 9(10), e016223.
 [http://dx.doi.org/10.1161/JAHA.119.016223] [PMID: 32390485]

[120]
Li, Z.; Wu, Z.; Yan, J.; Liu, H.; Liu, Q.; Deng, Y.; Ou, C.; Chen, M. Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis. Lab. Invest.,  2019, 99(3), 346-357.
 [http://dx.doi.org/10.1038/s41374-018-0091-y] [PMID: 30068915]

[121]
Videja, M.; Vilskersts, R.; Korzh, S.; Cirule, H.; Sevostjanovs, E.; Dambrova, M.; Makrecka-Kuka, M. Microbiota-derived metabolite trimethylamine n-oxide protects mitochondrial energy metabolism and cardiac functionality in a rat model of right ventricle heart failure. Front. Cell Dev. Biol.,  2021, 8, 622741.
 [http://dx.doi.org/10.3389/fcell.2020.622741] [PMID: 33520996]

[122]
Gawrys-Kopczynska, M.; Konop, M.; Maksymiuk, K.; Kraszewska, K.; Derzsi, L.; Sozanski, K.; Holyst, R.; Pilz, M.; Samborowska, E.; Dobrowolski, L.; Jaworska, K.; Mogilnicka, I.; Ufnal, M. TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats. eLife,  2020, 9, e57028.
 [http://dx.doi.org/10.7554/eLife.57028] [PMID: 32510330]

[123]
Brunt, V.E.; Gioscia-Ryan, R.A.; Casso, A.G.; VanDongen, N.S.; Ziemba, B.P.; Sapinsley, Z.J.; Richey, J.J.; Zigler, M.C.; Neilson, A.P.; Davy, K.P.; Seals, D.R. Trimethylamine-n-oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans. Hypertension,  2020, 76(1), 101-112.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14759] [PMID: 32520619]

[124]
Zhang, X.; Li, Y.; Yang, P.; Liu, X.; Lu, L.; Chen, Y.; Zhong, X.; Li, Z.; Liu, H.; Ou, C.; Yan, J.; Chen, M. Trimethylamine-n-oxide promotes vascular calcification through activation of nlrp3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and nf-κb (nuclear factor κb) signals. Arterioscler. Thromb. Vasc. Biol.,  2020, 40(3), 751-765.
 [http://dx.doi.org/10.1161/ATVBAHA.119.313414] [PMID: 31941382]

[125]
Li, Y.; Zhang, L.; Ren, P.; Yang, Y.; Li, S.; Qin, X.; Zhang, M.; Zhou, M.; Liu, W. Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation. Phytomedicine,  2021, 93, 153812.
 [http://dx.doi.org/10.1016/j.phymed.2021.153812] [PMID: 34753029]

[126]
Fedotcheva, N.; Olenin, A.; Beloborodova, N. Influence of microbial metabolites on the nonspecific permeability of mitochondrial membranes under conditions of acidosis and loading with calcium and iron ions. Biomedicines,  2021, 9(5), 558.
 [http://dx.doi.org/10.3390/biomedicines9050558] [PMID: 34067718]

[127]
Witkowski, M.; Witkowski, M.; Friebel, J.; Buffa, J.A.; Li, X.S.; Wang, Z.; Sangwan, N.; Li, L.; DiDonato, J.A.; Tizian, C.; Haghikia, A.; Kirchhofer, D.; Mach, F.; Räber, L.; Matter, C.M.; Tang, W.H.W.; Landmesser, U.; Lüscher, T.F.; Rauch, U.; Hazen, S.L. Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis. Cardiovasc. Res.,  2022, 118(10), 2367-2384.
 [http://dx.doi.org/10.1093/cvr/cvab263] [PMID: 34352109]

[128]
Steinke, I.; Ghanei, N.; Govindarajulu, M.; Yoo, S.; Zhong, J.; Amin, R.H. Drug discovery and development of novel therapeutics for inhibiting tmao in models of atherosclerosis and diabetes. Front. Physiol.,  2020, 11, 567899.
 [http://dx.doi.org/10.3389/fphys.2020.567899] [PMID: 33192565]

[129]
Wu, P.; Chen, J.; Chen, J.; Tao, J.; Wu, S.; Xu, G.; Wang, Z.; Wei, D.; Yin, W. Trimethylamine N-oxide promotes apoE −/− mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. J. Cell. Physiol.,  2020, 235(10), 6582-6591.
 [http://dx.doi.org/10.1002/jcp.29518] [PMID: 32012263]

[130]
Papandreou, C.; Bulló, M.; Hernández-Alonso, P.; Ruiz-Canela, M.; Li, J.; Guasch-Ferré, M.; Toledo, E.; Clish, C.; Corella, D.; Estruch, R.; Ros, E.; Fitó, M.; Alonso-Gómez, A.; Fiol, M.; Santos-Lozano, J.M.; Serra-Majem, L.; Liang, L.; Martínez-González, M.A.; Hu, F.B.; Salas-Salvadó, J. Choline metabolism and risk of atrial fibrillation and heart failure in the PREDIMED study. Clin. Chem.,  2021, 67(1), 288-297.
 [http://dx.doi.org/10.1093/clinchem/hvaa224] [PMID: 33257943]

[131]
Wei, H.; Zhao, M.; Huang, M.; Li, C.; Gao, J.; Yu, T.; Zhang, Q.; Shen, X.; Ji, L.; Ni, L.; Zhao, C.; Wang, Z.; Dong, E.; Zheng, L.; Wang, D.W. FMO3-TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population. Front. Med.,  2022, 16(2), 295-305.
 [http://dx.doi.org/10.1007/s11684-021-0857-2] [PMID: 34159537]

[132]
Huang, K.; Wang, Y.; Bai, Y.; Luo, Q.; Lin, X.; Yang, Q.; Wang, S.; Xin, H. Gut microbiota and metabolites in atrial fibrillation patients and their changes after catheter ablation. Microbiol. Spectr.,  2022, 10(2), e01077-21.
 [http://dx.doi.org/10.1128/spectrum.01077-21] [PMID: 35384710]

[133]
Svingen, G.F.T.; Zuo, H.; Ueland, P.M.; Seifert, R.; Løland, K.H.; Pedersen, E.R.; Schuster, P.M.; Karlsson, T.; Tell, G.S.; Schartum-Hansen, H.; Olset, H.; Svenningsson, M.; Strand, E.; Nilsen, D.W.; Nordrehaug, J.E.; Dhar, I.; Nygård, O. Increased plasma trimethylamine- N -oxide is associated with incident atrial fibrillation. Int. J. Cardiol.,  2018, 267, 100-106.
 [http://dx.doi.org/10.1016/j.ijcard.2018.04.128] [PMID: 29957250]

[134]
Nguyen, B.O.; Meems, L.M.G.; van Faassen, M.; Crijns, H.J.G.M.; van Gelder, I.C.; Kuipers, F.; Rienstra, M. Gut-microbe derived TMAO and its association with more progressed forms of AF: Results from the AF-RISK study. Int. J. Cardiol. Heart Vasc.,  2021, 34, 100798.
 [http://dx.doi.org/10.1016/j.ijcha.2021.100798] [PMID: 34095450]

[135]
Zuo, K.; Yin, X.; Li, K.; Zhang, J.; Wang, P.; Jiao, J.; Liu, Z.; Liu, X.; Liu, J.; Li, J.; Yang, X. Different types of atrial fibrillation share patterns of gut microbiota dysbiosis. MSphere,  2020, 5(2), e00071-20.
 [http://dx.doi.org/10.1128/mSphere.00071-20] [PMID: 32188747]

[136]
Yu, L.; Meng, G.; Huang, B.; Zhou, X.; Stavrakis, S.; Wang, M.; Li, X.; Zhou, L.; Wang, Y.; Wang, M.; Wang, Z.; Deng, J.; Po, S.S.; Jiang, H. A potential relationship between gut microbes and atrial fibrillation: Trimethylamine N-oxide, a gut microbe-derived metabolite, facilitates the progression of atrial fibrillation. Int. J. Cardiol.,  2018, 255, 92-98.
 [http://dx.doi.org/10.1016/j.ijcard.2017.11.071] [PMID: 29425570]

[137]
Yang, W.; Zhao, Q.; Yao, M.; Li, X.; Shan, Z.; Wang, Y. The transformation of atrial fibroblasts into myofibroblasts is promoted by trimethylamine N-oxide via the Wnt3a/β-catenin signaling pathway. J. Thorac. Dis.,  2022, 14(5), 1526-1536.
 [http://dx.doi.org/10.21037/jtd-22-475] [PMID: 35693618]

[138]
Subramaniam, S.; Fletcher, C. Trimethylamine N-oxide: breathe new life. Br. J. Pharmacol.,  2018, 175(8), 1344-1353.
 [http://dx.doi.org/10.1111/bph.13959] [PMID: 28745401]

[139]
Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem.,  2003, 72(1), 137-174.
 [http://dx.doi.org/10.1146/annurev.biochem.72.121801.161712] [PMID: 12543708]

[140]
Ridlon, J.M.; Kang, D.J.; Hylemon, P.B. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res.,  2006, 47(2), 241-259.
 [http://dx.doi.org/10.1194/jlr.R500013-JLR200] [PMID: 16299351]

[141]
Lefebvre, P.; Cariou, B.; Lien, F.; Kuipers, F.; Staels, B. Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev.,  2009, 89(1), 147-191.
 [http://dx.doi.org/10.1152/physrev.00010.2008] [PMID: 19126757]

[142]
Wahlström, A.; Sayin, S.I.; Marschall, H.U.; Bäckhed, F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab.,  2016, 24(1), 41-50.
 [http://dx.doi.org/10.1016/j.cmet.2016.05.005] [PMID: 27320064]

[143]
Li, R.; Andreu-Sánchez, S.; Kuipers, F.; Fu, J. Gut microbiome and bile acids in obesity-related diseases. Best Pract. Res. Clin. Endocrinol. Metab.,  2021, 35(3), 101493.
 [http://dx.doi.org/10.1016/j.beem.2021.101493] [PMID: 33707081]

[144]
Kim, G.B.; Miyamoto, C.M.; Meighen, E.A.; Lee, B.H. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidum strains. Appl. Environ. Microbiol.,  2004, 70(9), 5603-5612.
 [http://dx.doi.org/10.1128/AEM.70.9.5603-5612.2004] [PMID: 15345449]

[145]
Coleman, J.P.; Hudson, L.L. Cloning and characterization of a conjugated bile acid hydrolase gene from Clostridium perfringens. Appl. Environ. Microbiol.,  1995, 61(7), 2514-2520.
 [http://dx.doi.org/10.1128/aem.61.7.2514-2520.1995] [PMID: 7618863]

[146]
Dussurget, O.; Cabanes, D.; Dehoux, P.; Lecuit, M.; Buchrieser, C.; Glaser, P.; Cossart, P. Listeria monocytogenes bile salt hydrolase is a PrfA‐regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol. Microbiol.,  2002, 45(4), 1095-1106.
 [http://dx.doi.org/10.1046/j.1365-2958.2002.03080.x] [PMID: 12180927]

[147]
Begley, M.; Sleator, R.D.; Gahan, C.G.M.; Hill, C. Contribution of three bile-associated loci, bsh, pva, and btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes. Infect. Immun.,  2005, 73(2), 894-904.
 [http://dx.doi.org/10.1128/IAI.73.2.894-904.2005] [PMID: 15664931]

[148]
Wang, Z.; Zeng, X.; Mo, Y.; Smith, K.; Guo, Y.; Lin, J. Identification and characterization of a bile salt hydrolase from Lactobacillus salivarius for development of novel alternatives to antibiotic growth promoters. Appl. Environ. Microbiol.,  2012, 78(24), 8795-8802.
 [http://dx.doi.org/10.1128/AEM.02519-12] [PMID: 23064348]

[149]
Corzo, G.; Gilliland, S.E. Bile salt hydrolase activity of three strains of Lactobacillus acidophilus. J. Dairy Sci.,  1999, 82(3), 472-480.
 [http://dx.doi.org/10.3168/jds.S0022-0302(99)75256-2] [PMID: 10194664]

[150]
Stellwag, E.J.; Hylemon, P.B. Purification and characterization of bile salt hydrolase from Bacteroides fragilis Subsp. Fragilis. Enzymol.,  1976, 452(1), 165-176.
 [http://dx.doi.org/10.1016/0005-2744(76)90068-1]

[151]
Kuipers, F.; Bloks, V.W.; Groen, A.K. Beyond intestinal soap—bile acids in metabolic control. Nat. Rev. Endocrinol.,  2014, 10(8), 488-498.
 [http://dx.doi.org/10.1038/nrendo.2014.60] [PMID: 24821328]

[152]
Khurana, S.; Raufman, J.P.; Pallone, T.L. Bile acids regulate cardiovascular function. Clin. Transl. Sci.,  2011, 4(3), 210-218.
 [http://dx.doi.org/10.1111/j.1752-8062.2011.00272.x] [PMID: 21707953]

[153]
Chiang, J.Y.L. Bile acid metabolism and signaling. Compr. Physiol.,  2013, 3(3), 1191-1212.
 [http://dx.doi.org/10.1002/cphy.c120023] [PMID: 23897684]

[154]
Porez, G.; Prawitt, J.; Gross, B.; Staels, B. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J. Lipid Res.,  2012, 53(9), 1723-1737.
 [http://dx.doi.org/10.1194/jlr.R024794] [PMID: 22550135]

[155]
Ahmad, T.R.; Haeusler, R.A. Bile acids in glucose metabolism and insulin signalling — mechanisms and research needs. Nat. Rev. Endocrinol.,  2019, 15(12), 701-712.
 [http://dx.doi.org/10.1038/s41574-019-0266-7] [PMID: 31616073]

[156]
Haghikia, A.; Zimmermann, F.; Schumann, P.; Jasina, A.; Roessler, J.; Schmidt, D.; Heinze, P.; Kaisler, J.; Nageswaran, V.; Aigner, A.; Ceglarek, U.; Cineus, R.; Hegazy, A.N.; van der Vorst, E.P.C.; Döring, Y.; Strauch, C.M.; Nemet, I.; Tremaroli, V.; Dwibedi, C.; Kränkel, N.; Leistner, D.M.; Heimesaat, M.M.; Bereswill, S.; Rauch, G.; Seeland, U.; Soehnlein, O.; Müller, D.N.; Gold, R.; Bäckhed, F.; Hazen, S.L.; Haghikia, A.; Landmesser, U. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism. Eur. Heart J.,  2022, 43(6), 518-533.
 [http://dx.doi.org/10.1093/eurheartj/ehab644] [PMID: 34597388]

[157]
Vasavan, T.; Ferraro, E.; Ibrahim, E.; Dixon, P.; Gorelik, J.; Williamson, C. Heart and bile acids – Clinical consequences of altered bile acid metabolism. Biochim. Biophys. Acta Mol. Basis Dis.,  2018, 1864(4), 1345-1355.
 [http://dx.doi.org/10.1016/j.bbadis.2017.12.039] [PMID: 29317337]

[158]
Schmid, A.; Schlegel, J.; Thomalla, M.; Karrasch, T.; Schäffler, A. Evidence of functional bile acid signaling pathways in adipocytes. Mol. Cell. Endocrinol.,  2019, 483, 1-10.
 [http://dx.doi.org/10.1016/j.mce.2018.12.006] [PMID: 30543876]

[159]
Byun, S.; Jung, H.; Chen, J.; Kim, Y.C.; Kim, D.H.; Kong, B.; Guo, G.; Kemper, B.; Kemper, J.K. Phosphorylation of hepatic farnesoid X receptor by FGF19 signaling–activated Src maintains cholesterol levels and protects from atherosclerosis. J. Biol. Chem.,  2019, 294(22), 8732-8744.
 [http://dx.doi.org/10.1074/jbc.RA119.008360] [PMID: 30996006]

[160]
Xu, Y.; Li, F.; Zalzala, M.; Xu, J.; Gonzalez, F.J.; Adorini, L.; Lee, Y.K.; Yin, L.; Zhang, Y.; Farnesoid, X. Receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice. Hepatology,  2016, 64(4), 1072-1085.
 [http://dx.doi.org/10.1002/hep.28712] [PMID: 27359351]

[161]
Wu, Q.; Sun, L.; Hu, X.; Wang, X.; Xu, F.; Chen, B.; Liang, X.; Xia, J.; Wang, P.; Aibara, D.; Zhang, S.; Zeng, G.; Yun, C.; Yan, Y.; Zhu, Y.; Bustin, M.; Zhang, S.; Gonzalez, F.J.; Jiang, C. Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis. J. Clin. Invest.,  2021, 131(9), e142865.
 [http://dx.doi.org/10.1172/JCI142865] [PMID: 33938457]

[162]
Pushpass, R.A.G.; Alzoufairi, S.; Jackson, K.G.; Lovegrove, J.A. Circulating bile acids as a link between the gut microbiota and cardiovascular health: impact of prebiotics, probiotics and polyphenol-rich foods. Nutr. Res. Rev.,  2022, 35(2), 161-180.
 [http://dx.doi.org/10.1017/S0954422421000081] [PMID: 33926590]

[163]
Ghosh, S.; Dass, J.F.P. Study of pathway cross-talk interactions with NF-κB leading to its activation via ubiquitination or phosphorylation: A brief review. Gene,  2016, 584(1), 97-109.
 [http://dx.doi.org/10.1016/j.gene.2016.03.008] [PMID: 26968890]

[164]
Fu, Y.; Feng, H.; Ding, X.; Meng, Q.H.; Zhang, S.R.; Li, J.; Chao, Y.; Ji, T.T.; Bi, Y.H.; Zhang, W.W.; Chen, Q.; Zhang, Y.H.; Feng, Y.L.; Bian, H.M. Alisol B 23-acetate adjusts bile acid metabolisim via hepatic FXR-BSEP signaling activation to alleviate atherosclerosis. Phytomedicine,  2022, 101, 154120.
 [http://dx.doi.org/10.1016/j.phymed.2022.154120] [PMID: 35523117]

[165]
Huang, K.; Liu, C.; Peng, M.; Su, Q.; Liu, R.; Guo, Z.; Chen, S.; Li, Z.; Chang, G. Glycoursodeoxycholic acid ameliorates atherosclerosis and alters gut microbiota in apolipoprotein e–deficient mice. J. Am. Heart Assoc.,  2021, 10(7), e019820.
 [http://dx.doi.org/10.1161/JAHA.120.019820] [PMID: 33787322]

[166]
Ryan, P.M.; Stanton, C.; Caplice, N.M. Bile acids at the cross-roads of gut microbiome–host cardiometabolic interactions. Diabetol. Metab. Syndr.,  2017, 9(1), 102.
 [http://dx.doi.org/10.1186/s13098-017-0299-9] [PMID: 29299069]

[167]
Hanafi, N.I.; Mohamed, A.S.; Sheikh Abdul Kadir, S.H.; Othman, M.H.D. Overview of bile acids signaling and perspective on the signal of ursodeoxycholic acid, the most hydrophilic bile acid, in the heart. Biomolecules,  2018, 8(4), 159.
 [http://dx.doi.org/10.3390/biom8040159] [PMID: 30486474]

[168]
Kida, T.; Tsubosaka, Y.; Hori, M.; Ozaki, H.; Murata, T. Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol.,  2013, 33(7), 1663-1669.
 [http://dx.doi.org/10.1161/ATVBAHA.113.301565] [PMID: 23619297]

[169]
Chung, J.; An, S.H.; Kang, S.W.; Kwon, K. Ursodeoxycholic Acid (UDCA) exerts anti-atherogenic effects by inhibiting rage signaling in diabetic atherosclerosis. PLoS One,  2016, 11(1), e0147839.
 [http://dx.doi.org/10.1371/journal.pone.0147839] [PMID: 26807573]

[170]
Chung, J.; Kim, K.H.; Lee, S.C.; An, S.H.; Kwon, K. Ursodeoxycholic Acid (UDCA) exerts anti-atherogenic effects by inhibiting endoplasmic reticulum (ER) stress induced by disturbed flow. Mol. Cells,  2015, 38(10), 851-858.
 [http://dx.doi.org/10.14348/molcells.2015.0094] [PMID: 26442866]

[171]
Hanafi, N.I.; Mohamed, A.S.; Md Noor, J.; Abdul Hamid Hasani, N.; Siran, R.; Osman, N.J.; Ab Rahim, S.; Sheikh Abdul Kadir, S.H.; Sheikh Abdul Kadir, S.H. Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2. Genet. Mol. Res.,  2016, 15(2)
 [http://dx.doi.org/10.4238/gmr.15028150] [PMID: 27323195]

[172]
Chen, H.; Li, J.; Li, N.; Liu, H.; Tang, J. Increased circulating trimethylamine N-oxide plays a contributory role in the development of endothelial dysfunction and hypertension in the RUPP rat model of preeclampsia. Hypertens. Pregnancy,  2019, 38(2), 96-104.
 [http://dx.doi.org/10.1080/10641955.2019.1584630] [PMID: 30821524]

[173]
Schwabl, P.; Hambruch, E.; Seeland, B.A.; Hayden, H.; Wagner, M.; Garnys, L.; Strobel, B.; Schubert, T.L.; Riedl, F.; Mitteregger, D.; Burnet, M.; Starlinger, P.; Oberhuber, G.; Deuschle, U.; Rohr-Udilova, N.; Podesser, B.K.; Peck-Radosavljevic, M.; Reiberger, T.; Kremoser, C.; Trauner, M. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction. J. Hepatol.,  2017, 66(4), 724-733.
 [http://dx.doi.org/10.1016/j.jhep.2016.12.005] [PMID: 27993716]

[174]
Kida, T.; Omori, K.; Hori, M.; Ozaki, H.; Murata, T. Stimulation of G protein-coupled bile acid receptor enhances vascular endothelial barrier function via activation of protein kinase A and Rac1. J. Pharmacol. Exp. Ther.,  2014, 348(1), 125-130.
 [http://dx.doi.org/10.1124/jpet.113.209288] [PMID: 24144793]

[175]
Fiorucci, S.; Zampella, A.; Cirino, G.; Bucci, M.; Distrutti, E. Decoding the vasoregulatory activities of bile acid-activated receptors in systemic and portal circulation: Role of gaseous mediators. Am. J. Physiol. Heart Circ. Physiol.,  2017, 312(1), H21-H32.
 [http://dx.doi.org/10.1152/ajpheart.00577.2016] [PMID: 27765751]

[176]
Li, S.; Li, C.; Wang, W. Bile acid signaling in renal water regulation. Am. J. Physiol. Renal Physiol.,  2019, 317(1), F73-F76.
 [http://dx.doi.org/10.1152/ajprenal.00563.2018] [PMID: 31091123]

[177]
Herman-Edelstein, M.; Weinstein, T.; Levi, M. Bile acid receptors and the kidney. Curr. Opin. Nephrol. Hypertens.,  2018, 27(1), 56-62.
 [http://dx.doi.org/10.1097/MNH.0000000000000374] [PMID: 29045336]

[178]
Huc, T.; Jurkowska, H.; Wróbel, M.; Jaworska, K.; Onyszkiewicz, M.; Ufnal, M. Colonic hydrogen sulfide produces portal hypertension and systemic hypotension in rats. Exp. Biol. Med.,  2018, 243(1), 96-106.
 [http://dx.doi.org/10.1177/1535370217741869] [PMID: 29130338]

[179]
Verhaar, B.J.H.; Prodan, A.; Nieuwdorp, M.; Muller, M. Gut microbiota in hypertension and atherosclerosis: A review. Nutrients,  2020, 12(10), 2982.
 [http://dx.doi.org/10.3390/nu12102982] [PMID: 33003455]

[180]
D’Agati, V.D.; Chagnac, A.; de Vries, A.P.J.; Levi, M.; Porrini, E.; Herman-Edelstein, M.; Praga, M. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat. Rev. Nephrol.,  2016, 12(8), 453-471.
 [http://dx.doi.org/10.1038/nrneph.2016.75] [PMID: 27263398]

[181]
Cheng, L.; Huang, C.; Chen, Z. Tauroursodeoxycholic acid ameliorates lipopolysaccharide-induced depression like behavior in mice via the inhibition of neuroinflammation and oxido-nitrosative stress. Pharmacology,  2019, 103(1-2), 93-100.
 [http://dx.doi.org/10.1159/000494139] [PMID: 30517939]

[182]
Mayerhofer, C.C.K.; Ueland, T.; Broch, K.; Vincent, R.P.; Cross, G.F.; Dahl, C.P.; Aukrust, P.; Gullestad, L.; Hov, J.R.; Trøseid, M. Increased secondary/primary bile acid ratio in chronic heart failure. J. Card. Fail.,  2017, 23(9), 666-671.
 [http://dx.doi.org/10.1016/j.cardfail.2017.06.007] [PMID: 28688889]

[183]
Kinugasa, Y.; Nakamura, K.; Kamitani, H.; Hirai, M.; Yanagihara, K.; Kato, M.; Yamamoto, K. Trimethylamine N-oxide and outcomes in patients hospitalized with acute heart failure and preserved ejection fraction. ESC Heart Fail.,  2021, 8(3), 2103-2110.
 [http://dx.doi.org/10.1002/ehf2.13290] [PMID: 33734604]

[184]
Xu, J.; Li, X.; Zhang, F.; Tang, L.; Wei, J.; Lei, X.; Wang, H.; Zhang, Y.; Li, D.; Tang, X.; Li, G.; Tang, S.; Wu, H.; Yang, H. 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, 10, 1474.
 [http://dx.doi.org/10.3389/fphar.2019.01474] [PMID: 31866870]

[185]
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.
 [http://dx.doi.org/10.1002/jssc.202000622] [PMID: 33001559]

[186]
Xia, Y.; Zhang, F.; Zhao, S.; Li, Y.; Chen, X.; Gao, E.; Xu, X.; Xiong, Z.; Zhang, X.; Zhang, J.; Zhao, H.; Wang, W.; Wang, H.; Guo, Y.; Liu, Y.; Li, C.; Wang, S.; Zhang, L.; Yan, W.; Tao, L. Adiponectin determines farnesoid X receptor agonism-mediated cardioprotection against post-infarction remodelling and dysfunction. Cardiovasc. Res.,  2018, 114(10), 1335-1349.
 [http://dx.doi.org/10.1093/cvr/cvy093] [PMID: 29668847]

[187]
von Haehling, S.; Schefold, J.C.; Jankowska, E.A.; Springer, J.; Vazir, A.; Kalra, P.R.; Sandek, A.; Fauler, G.; Stojakovic, T.; Trauner, M.; Ponikowski, P.; Volk, H.D.; Doehner, W.; Coats, A.J.S.; Poole-Wilson, P.A.; Anker, S.D. 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.
 [http://dx.doi.org/10.1016/j.jacc.2011.10.880] [PMID: 22300693]

[188]
Wang, X.; Li, Z.; Zang, M.; Yao, T.; Mao, J.; Pu, J. Circulating primary bile acid is correlated with structural remodeling in atrial fibrillation. J. Interv. Card. Electrophysiol.,  2020, 57(3), 371-377.
 [http://dx.doi.org/10.1007/s10840-019-00540-z] [PMID: 30915593]

[189]
Alonso, A.; Yu, B.; Qureshi, W.T.; Grams, M.E.; Selvin, E.; Soliman, E.Z.; Loehr, L.R.; Chen, L.Y.; Agarwal, S.K.; Alexander, D.; Boerwinkle, E. Metabolomics and incidence of atrial fibrillation in african americans: The atherosclerosis risk in communities (ARIC) study. PLoS One,  2015, 10(11), e0142610.
 [http://dx.doi.org/10.1371/journal.pone.0142610] [PMID: 26544570]

[190]
Rainer, P.P.; Primessnig, U.; Harenkamp, S.; Doleschal, B.; Wallner, M.; Fauler, G.; Stojakovic, T.; Wachter, R.; Yates, A.; Groschner, K.; Trauner, M.; Pieske, B.M.; von Lewinski, D. Bile acids induce arrhythmias in human atrial myocardium—implications for altered serum bile acid composition in patients with atrial fibrillation. Heart,  2013, 99(22), 1685-1692.
 [http://dx.doi.org/10.1136/heartjnl-2013-304163] [PMID: 23894089]

[191]
Kawamata, Y.; Fujii, R.; Hosoya, M.; Harada, M.; Yoshida, H.; Miwa, M.; Fukusumi, S.; Habata, Y.; Itoh, T.; Shintani, Y.; Hinuma, S.; Fujisawa, Y.; Fujino, M. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem.,  2003, 278(11), 9435-9440.
 [http://dx.doi.org/10.1074/jbc.M209706200] [PMID: 12524422]

[192]
Sheikh Abdul Kadir, S.H.; Miragoli, M.; Abu-Hayyeh, S.; Moshkov, A.V.; Xie, Q.; Keitel, V.; Nikolaev, V.O.; Williamson, C.; Gorelik, J. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One,  2010, 5(3), e9689.
 [http://dx.doi.org/10.1371/journal.pone.0009689] [PMID: 20300620]

[193]
Swales, K.E.; Moore, R.; Truss, N.J.; Tucker, A.; Warner, T.D.; Negishi, M.; Bishop-Bailey, D.; Pregnane, X. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress. Cardiovasc. Res.,  2012, 93(4), 674-681.
 [http://dx.doi.org/10.1093/cvr/cvr330] [PMID: 22166712]

[194]
Sun, H.; Olson, K.C.; Gao, C.; Prosdocimo, D.A.; Zhou, M.; Wang, Z.; Jeyaraj, D.; Youn, J.Y.; Ren, S.; Liu, Y.; Rau, C.D.; Shah, S.; Ilkayeva, O.; Gui, W.J.; William, N.S.; Wynn, R.M.; Newgard, C.B.; Cai, H.; Xiao, X.; Chuang, D.T.; Schulze, P.C.; Lynch, C.; Jain, M.K.; Wang, Y. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation,  2016, 133(21), 2038-2049.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020226] [PMID: 27059949]

[195]
Li, T.; Zhang, Z.; Kolwicz, S.C., Jr; Abell, L.; Roe, N.D.; Kim, M.; Zhou, B.; Cao, Y.; Ritterhoff, J.; Gu, H.; Raftery, D.; Sun, H.; Tian, R. Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury. Cell Metab.,  2017, 25(2), 374-385.
 [http://dx.doi.org/10.1016/j.cmet.2016.11.005] [PMID: 28178567]

[196]
Li, Y.; Xiong, Z.; Yan, W.; Gao, E.; Cheng, H.; Wu, G.; Liu, Y.; Zhang, L.; Li, C.; Wang, S.; Fan, M.; Zhao, H.; Zhang, F.; Tao, L. Branched chain amino acids exacerbate myocardial ischemia/reperfusion vulnerability via enhancing GCN2/ATF6/PPAR-α pathway-dependent fatty acid oxidation. Theranostics,  2020, 10(12), 5623-5640.
 [http://dx.doi.org/10.7150/thno.44836] [PMID: 32373236]

[197]
McGarrah, R.W.; White, P.J. Branched-chain amino acids in cardiovascular disease. Nat. Rev. Cardiol.,  2023, 20(2), 77-89.
 [http://dx.doi.org/10.1038/s41569-022-00760-3] [PMID: 36064969]

[198]
Xiong, Y.; Jiang, L.; Li, T. Aberrant branched-chain amino acid catabolism in cardiovascular diseases. Front. Cardiovasc. Med.,  2022, 9, 965899.
 [http://dx.doi.org/10.3389/fcvm.2022.965899] [PMID: 35911554]

[199]
Konopelski, P.; Mogilnicka, I. Biological effects of indole-3-propionic acid, a gut microbiota-derived metabolite, and its precursor tryptophan in mammals’ health and disease. Int. J. Mol. Sci.,  2022, 23(3), 1222.
 [http://dx.doi.org/10.3390/ijms23031222] [PMID: 35163143]

[200]
Agus, A.; Planchais, J.; Sokol, H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe,  2018, 23(6), 716-724.
 [http://dx.doi.org/10.1016/j.chom.2018.05.003] [PMID: 29902437]

[201]
Liu, J.R.; Miao, H.; Deng, D.Q.; Vaziri, N.D.; Li, P.; Zhao, Y.Y. Gut microbiota-derived tryptophan metabolism mediates renal fibrosis by aryl hydrocarbon receptor signaling activation. Cell. Mol. Life Sci.,  2021, 78(3), 909-922.
 [http://dx.doi.org/10.1007/s00018-020-03645-1] [PMID: 32965514]

[202]
Niinisalo, P.; Oksala, N.; Levula, M.; Pelto-Huikko, M.; Järvinen, O.; Salenius, J.P.; Kytömäki, L.; Soini, J.T.; Kähönen, M.; Laaksonen, R.; Hurme, M.; Lehtimäki, T. Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere Vascular Study. Ann. Med.,  2010, 42(1), 55-63.
 [http://dx.doi.org/10.3109/07853890903321559] [PMID: 19941414]

[203]
Song, P.; Ramprasath, T.; Wang, H.; Zou, M.H. Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases. Cell. Mol. Life Sci.,  2017, 74(16), 2899-2916.
 [http://dx.doi.org/10.1007/s00018-017-2504-2] [PMID: 28314892]

[204]
Sanchez-Gimenez, R.; Ahmed-Khodja, W.; Molina, Y.; Peiró, O.M.; Bonet, G.; Carrasquer, A.; Fragkiadakis, G.A.; Bulló, M.; Bardaji, A.; Papandreou, C. Gut microbiota-derived metabolites and cardiovascular disease risk: A systematic review of prospective cohort studies. Nutrients,  2022, 14(13), 2654.
 [http://dx.doi.org/10.3390/nu14132654] [PMID: 35807835]

[205]
Barreto, F.C.; Barreto, D.V.; Liabeuf, S.; Meert, N.; Glorieux, G.; Temmar, M.; Choukroun, G.; Vanholder, R.; Massy, Z.A. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin. J. Am. Soc. Nephrol.,  2009, 4(10), 1551-1558.
 [http://dx.doi.org/10.2215/CJN.03980609] [PMID: 19696217]

[206]
Koike, H.; Morita, T.; Tatebe, J.; Watanabe, I.; Koike, M.; Yao, S.; Shinohara, M.; Yuzawa, H.; Suzuki, T.; Fujino, T.; Ikeda, T. The relationship between serum indoxyl sulfate and the renal function after catheter ablation of atrial fibrillation in patients with mild renal dysfunction. Heart Vessels,  2019, 34(4), 641-649.
 [http://dx.doi.org/10.1007/s00380-018-1288-0] [PMID: 30406286]

[207]
Dou, L.; Jourde-Chiche, N.; Faure, V.; Cerini, C.; Berland, Y.; Dignat-George, F.; Brunet, P. The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells. J. Thromb. Haemost.,  2007, 5(6), 1302-1308.
 [http://dx.doi.org/10.1111/j.1538-7836.2007.02540.x] [PMID: 17403109]

[208]
Huć, T.; Nowinski, A.; Drapala, A.; Konopelski, P.; Ufnal, M. Indole and indoxyl sulfate, gut bacteria metabolites of tryptophan, change arterial blood pressure via peripheral and central mechanisms in rats. Pharmacol. Res.,  2018, 130, 172-179.
 [http://dx.doi.org/10.1016/j.phrs.2017.12.025] [PMID: 29287686]

[209]
Imazu, M.; Fukuda, H.; Kanzaki, H.; Amaki, M.; Hasegawa, T.; Takahama, H.; Hitsumoto, T.; Tsukamoto, O.; Morita, T.; Ito, S.; Kitakaze, M. Plasma indoxyl sulfate levels predict cardiovascular events in patients with mild chronic heart failure. Sci. Rep.,  2020, 10(1), 16528.
 [http://dx.doi.org/10.1038/s41598-020-73633-9] [PMID: 33020564]

[210]
Lekawanvijit, S.; Adrahtas, A.; Kelly, D.J.; Kompa, A.R.; Wang, B.H.; Krum, H. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Eur. Heart J.,  2010, 31(14), 1771-1779.
 [http://dx.doi.org/10.1093/eurheartj/ehp574] [PMID: 20047993]

[211]
Yang, W.; Yu, T.; Huang, X.; Bilotta, A.J.; Xu, L.; Lu, Y.; Sun, J.; Pan, F.; Zhou, J.; Zhang, W.; Yao, S.; Maynard, C.L.; Singh, N.; Dann, S.M.; Liu, Z.; Cong, Y. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat. Commun.,  2020, 11(1), 4457.
 [http://dx.doi.org/10.1038/s41467-020-18262-6] [PMID: 32901017]

[212]
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.
 [http://dx.doi.org/10.1016/j.lfs.2013.05.008] [PMID: 23702423]

[213]
Camacho, O.; Rosales, M.C.; Shafi, T.; Fullman, J.; Plummer, N.S.; Meyer, T.W.; Sirich, T.L. Effect of a sustained difference in hemodialytic clearance on the plasma levels of p-cresol sulfate and indoxyl sulfate. Nephrol. Dial. Transplant.,  2016, 31(8), 1335-1341.
 [http://dx.doi.org/10.1093/ndt/gfw100] [PMID: 27190347]

[214]
Yang, K.; Xu, X.; Nie, L.; Xiao, T.; Guan, X.; He, T.; Yu, Y.; Liu, L.; Huang, Y.; Zhang, J.; Zhao, J. Indoxyl sulfate induces oxidative stress and hypertrophy in cardiomyocytes by inhibiting the AMPK/UCP2 signaling pathway. Toxicol. Lett.,  2015, 234(2), 110-119.
 [http://dx.doi.org/10.1016/j.toxlet.2015.01.021] [PMID: 25703824]

[215]
Gesper, M.; Nonnast, A.B.H.; Kumowski, N.; Stoehr, R.; Schuett, K.; Marx, N.; Kappel, B.A. Gut-derived metabolite indole-3-propionic acid modulates mitochondrial function in cardiomyocytes and alters cardiac function. Front. Med.,  2021, 8, 648259.
 [http://dx.doi.org/10.3389/fmed.2021.648259] [PMID: 33829028]

[216]
Fan, P.C.; Chang, J.C.H.; Lin, C.N.; Lee, C.C.; Chen, Y.T.; Chu, P.H.; Kou, G.; Lu, Y.A.; Yang, C.W.; Chen, Y.C. Serum indoxyl sulfate predicts adverse cardiovascular events in patients with chronic kidney disease. J. Formos. Med. Assoc.,  2019, 118(7), 1099-1106.
 [http://dx.doi.org/10.1016/j.jfma.2019.03.005] [PMID: 30928187]

[217]
Chen, W.T.; Chen, Y.C.; Hsieh, M.H.; Huang, S.Y.; Kao, Y.H.; Chen, Y.A.; Lin, Y.K.; Chen, S.A.; Chen, Y.J. The uremic toxin indoxyl sulfate increases pulmonary vein and atrial arrhythmogenesis. J. Cardiovasc. Electrophysiol.,  2015, 26(2), 203-210.
 [http://dx.doi.org/10.1111/jce.12554] [PMID: 25244538]

[218]
Yamagami, F.; Tajiri, K.; Doki, K.; Hattori, M.; Honda, J.; Aita, S.; Harunari, T.; Yamasaki, H.; Murakoshi, N.; Sekiguchi, Y.; Homma, M.; Takahashi, N.; Aonuma, K.; Nogami, A.; Ieda, M. Indoxyl sulphate is associated with atrial fibrillation recurrence after catheter ablation. Sci. Rep.,  2018, 8(1), 17276.
 [http://dx.doi.org/10.1038/s41598-018-35226-5] [PMID: 30467393]

[219]
Metghalchi, S.; Ponnuswamy, P.; Simon, T.; Haddad, Y.; Laurans, L.; Clément, M.; Dalloz, M.; Romain, M.; Esposito, B.; Koropoulis, V.; Lamas, B.; Paul, J.L.; Cottin, Y.; Kotti, S.; Bruneval, P.; Callebert, J.; den Ruijter, H.; Launay, J.M.; Danchin, N.; Sokol, H.; Tedgui, A.; Taleb, S.; Mallat, Z. Indoleamine 2,3-dioxygenase fine-tunes immune homeostasis in atherosclerosis and colitis through repression of interleukin-10 production. Cell Metab.,  2015, 22(3), 460-471.
 [http://dx.doi.org/10.1016/j.cmet.2015.07.004] [PMID: 26235422]

[220]
Ghoshal, S.; Witta, J.; Zhong, J.; de Villiers, W.; Eckhardt, E. Chylomicrons promote intestinal absorption of lipopolysaccharides. J. Lipid Res.,  2009, 50(1), 90-97.
 [http://dx.doi.org/10.1194/jlr.M800156-JLR200] [PMID: 18815435]

[221]
Carnevale, R.; Pastori, D.; Nocella, C.; Cammisotto, V.; Bartimoccia, S.; Novo, M.; Del Ben, M.; Farcomeni, A.; Angelico, F.; Violi, F. Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: Effect of extra-virgin olive oil. Eur. J. Nutr.,  2019, 58(2), 843-851.
 [http://dx.doi.org/10.1007/s00394-018-1718-x] [PMID: 29766292]

[222]
Manco, M.; Putignani, L.; Bottazzo, G.F. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr. Rev.,  2010, 31(6), 817-844.
 [http://dx.doi.org/10.1210/er.2009-0030] [PMID: 20592272]

[223]
Stoll, L.L.; Denning, G.M.; Weintraub, N.L. Potential role of endotoxin as a proinflammatory mediator of atherosclerosis. Arterioscler. Thromb. Vasc. Biol.,  2004, 24(12), 2227-2236.
 [http://dx.doi.org/10.1161/01.ATV.0000147534.69062.dc] [PMID: 15472123]

[224]
Levels, J.H.M.; Marquart, J.A.; Abraham, P.R.; van den Ende, A.E.; Molhuizen, H.O.F.; van Deventer, S.J.H.; Meijers, J.C.M. Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect. Immun.,  2005, 73(4), 2321-2326.
 [http://dx.doi.org/10.1128/IAI.73.4.2321-2326.2005] [PMID: 15784577]

[225]
Violi, F.; Cammisotto, V.; Bartimoccia, S.; Pignatelli, P.; Carnevale, R.; Nocella, C. Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease. Nat. Rev. Cardiol.,  2023, 20(1), 24-37.
 [http://dx.doi.org/10.1038/s41569-022-00737-2] [PMID: 35840742]

[226]
Wiedermann, C.J.; Kiechl, S.; Dunzendorfer, S.; Schratzberger, P.; Egger, G.; Oberhollenzer, F.; Willeit, J. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease. J. Am. Coll. Cardiol.,  1999, 34(7), 1975-1981.
 [http://dx.doi.org/10.1016/S0735-1097(99)00448-9] [PMID: 10588212]

[227]
Niebauer, J.; Volk, H.D.; Kemp, M.; Dominguez, M.; Schumann, R.R.; Rauchhaus, M.; Poole-Wilson, P.A.; Coats, A.J.S.; Anker, S.D.; Anker, S.D. Endotoxin and immune activation in chronic heart failure: A prospective cohort study. Lancet,  1999, 353(9167), 1838-1842.
 [http://dx.doi.org/10.1016/S0140-6736(98)09286-1] [PMID: 10359409]

[228]
Pastori, D.; Carnevale, R.; Nocella, C.; Novo, M.; Santulli, M.; Cammisotto, V.; Menichelli, D.; Pignatelli, P.; Violi, F. Gut‐derived serum lipopolysaccharide is associated with enhanced risk of major adverse cardiovascular events in atrial fibrillation: effect of adherence to mediterranean diet. J. Am. Heart Assoc.,  2017, 6(6), e005784.
 [http://dx.doi.org/10.1161/JAHA.117.005784] [PMID: 28584074]

[229]
Cani, P.D.; Bibiloni, R.; Knauf, C.; Waget, A.; Neyrinck, A.M.; Delzenne, N.M.; Burcelin, R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes,  2008, 57(6), 1470-1481.
 [http://dx.doi.org/10.2337/db07-1403] [PMID: 18305141]

[230]
Tomasova, L.; Konopelski, P.; Ufnal, M. Gut bacteria and hydrogen sulfide: The new old players in circulatory system homeostasis. Molecules,  2016, 21(11), 1558.
 [http://dx.doi.org/10.3390/molecules21111558] [PMID: 27869680]

[231]
Li, J.; Zhao, F.; Wang, Y.; Chen, J.; Tao, J.; Tian, G.; Wu, S.; Liu, W.; Cui, Q.; Geng, B.; Zhang, W.; Weldon, R.; Auguste, K.; Yang, L.; Liu, X.; Chen, L.; Yang, X.; Zhu, B.; Cai, J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome,  2017, 5(1), 14.
 [http://dx.doi.org/10.1186/s40168-016-0222-x] [PMID: 28143587]

[232]
Battson, M.L.; Lee, D.M.; Weir, T.L.; Gentile, C.L. The gut microbiota as a novel regulator of cardiovascular function and disease. J. Nutr. Biochem.,  2018, 56, 1-15.
 [http://dx.doi.org/10.1016/j.jnutbio.2017.12.010] [PMID: 29427903]

[233]
Okazaki, R.; Iwasaki, Y.; Miyauchi, Y.; Hirayama, Y.; Kobayashi, Y.; Katoh, T.; Mizuno, K.; Sekiguchi, A.; Yamashita, T. lipopolysaccharide induces atrial arrhythmogenesis via down-regulation of L-type Ca2+ channel genes in rats. Int. Heart J.,  2009, 50(3), 353-363.
 [http://dx.doi.org/10.1536/ihj.50.353] [PMID: 19506339]

[234]
Chen, Y.Y.; Sun, Z.W.; Jiang, J.P.; Kang, X.D.; Wang, L.L.; Shen, Y.L.; Xie, X.D.; Zheng, L.R. α-adrenoceptor-mediated enhanced inducibility of atrial fibrillation in a canine system inflammation model. Mol. Med. Rep.,  2017, 15(6), 3767-3774.
 [http://dx.doi.org/10.3892/mmr.2017.6477] [PMID: 28440455]

[235]
Kong, B.; Fu, H.; Xiao, Z.; Zhou, Y.; Shuai, W.; Huang, H. Gut microbiota dysbiosis induced by a high-fat diet increases susceptibility to atrial fibrillation. Cancer J. Cardiol.,  2022, 38(12), 1962-1975.
 [http://dx.doi.org/10.1016/j.cjca.2022.08.231] [PMID: 36084771]

[236]
Ke, Y.; Li, D.; Zhao, M.; Liu, C.; Liu, J.; Zeng, A.; Shi, X.; Cheng, S.; Pan, B.; Zheng, L.; Hong, H. Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radic. Biol. Med.,  2018, 116, 88-100.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2018.01.007] [PMID: 29325896]

[237]
Zhang, Y.; Zhang, S.; Li, B.; Luo, Y.; Gong, Y.; Jin, X.; Zhang, J.; Zhou, Y.; Zhuo, X.; Wang, Z.; Zhao, X.; Han, X.; Gao, Y.; Yu, H.; Liang, D.; Zhao, S.; Sun, D.; Wang, D.; Xu, W.; Qu, G.; Bo, W.; Li, D.; Wu, Y.; Li, Y. Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome. Cardiovasc. Res.,  2022, 118(3), 785-797.
 [http://dx.doi.org/10.1093/cvr/cvab114] [PMID: 33757127]

[238]
Kun, Z.; Jing, Z.; Chen, F.; Yuxing, W.; Lifeng, L.; Ye, L.; Zheng, L.; Yanjiang, W.; Liang, S.; Ying, T.; Xiandong, Y.; Xingpeng, L.; Xiaoqing, L.; Jiuchang, Z.; Kuibao, L.; Jing, L.; Xinchun, Y. Metagenomic data-analysis reveals enrichment of lipopolysaccharide synthesis in the gut microbiota of atrial fibrillation patients. Zhonghua Xin Xue Guan Bing Za Zhi,  2022, 50(3)
 [http://dx.doi.org/10.3760/cma.j.cn112148-20210106-00015]

[239]
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(5), 297.
 [http://dx.doi.org/10.3390/toxins13050297] [PMID: 33921975]

[240]
Nemet, I.; Saha, P.P.; Gupta, N.; Zhu, W.; Romano, K.A.; Skye, S.M.; Cajka, T.; Mohan, M.L.; Li, L.; Wu, Y.; Funabashi, M.; Ramer-Tait, A.E.; Naga Prasad, S.V.; Fiehn, O.; Rey, F.E.; Tang, W.H.W.; Fischbach, M.A.; DiDonato, J.A.; Hazen, S.L. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell,  2020, 180(5), 862-877.e22.
 [http://dx.doi.org/10.1016/j.cell.2020.02.016] [PMID: 32142679]

[241]
Chen, W.; Zhang, S.; Wu, J.; Ye, T.; Wang, S.; Wang, P.; Xing, D. Butyrate-producing bacteria and the gut-heart axis in atherosclerosis. Clin. Chim. Acta,  2020, 507, 236-241.
 [http://dx.doi.org/10.1016/j.cca.2020.04.037] [PMID: 32376324]

[242]
Huynh, K. Novel gut microbiota-derived metabolite promotes platelet thrombosis via adrenergic receptor signalling. Nat. Rev. Cardiol.,  2020, 17(5), 265.
 [http://dx.doi.org/10.1038/s41569-020-0367-y] [PMID: 32210404]

[243]
Dziewiecka, H.; Buttar, H.; Kasperska, A.; Ostapiuk-Karolczuk, J.; Domagalska, M.; Cichoń, J.; Skarpańska-Stejnborn, A. Physical activity induced alterations of gut microbiota in humans: A systematic review. 2022, 14(1), 122.
 [http://dx.doi.org/10.1186/s13102-022-00513-2] [PMID: 35799284]

[244]
Wang, T.; Zhang, Y.; Taaffe, D.R.; Kim, J.S.; Luo, H.; Yang, L.; Fairman, C.M.; Qiao, Y.; Newton, R.U.; Galvão, D.A. Protective effects of physical activity in colon cancer and underlying mechanisms: A review of epidemiological and biological evidence. Crit. Rev. Oncol. Hematol.,  2022, 170, 103578.
 [http://dx.doi.org/10.1016/j.critrevonc.2022.103578] [PMID: 35007701]

[245]
Amirsasan, R.; Akbarzadeh, M.; Akbarzadeh, S. Exercise and colorectal cancer: Prevention and molecular mechanisms. Cancer Cell Int.,  2022, 22(1), 247.
 [http://dx.doi.org/10.1186/s12935-022-02670-3] [PMID: 35945569]

[246]
Yu, C.; Liu, S.; Niu, Y.; Fu, L. Exercise protects intestinal epithelial barrier from high fat diet- induced permeabilization through SESN2/AMPKα1/HIF-1α signaling. J. Nutr. Biochem.,  2022, 107, 109059.
 [http://dx.doi.org/10.1016/j.jnutbio.2022.109059] [PMID: 35643285]

[247]
Barcelos, A.; Quintella, W.; Dalmacio, M.; Guimarães, S.; Dos Santos, A.M. Effects of intermittent fasting and physical activity on body mass and intestinal inflammation in rats fed a high-fat diet. Concilium,  2023, 23(8), 398-410.
 [http://dx.doi.org/10.53660/CLM-1263-23K16]

[248]
Wang, Y.; Chen, J.; Ni, Y.; Liu, Y.; Gao, X.; Panagiotou, G.; Xu, A. IDDF2023-ABS-0028 Integrative multi-omics reveal associations between gut mycobiome and metabolic benefits of physical exercise in obese individuals with prediabetes. Basic Gastroenterol.,  2023, 72(S1), A64.
 [http://dx.doi.org/10.1136/gutjnl-2023-IDDF.54]

[249]
Uchida, M.; Fujie, S.; Yano, H.; Iemitsu, M. Aerobic exercise training-induced alteration of gut microbiota composition affects endurance capacity. J. Physiol.,  2023, 601(12), 2329-2344.
 [http://dx.doi.org/10.1113/JP283995] [PMID: 37056044]

[250]
Jurdana, M.; Barlič Maganja, D. Regular Physical Activity Influences Gut Microbiota with Positive Health Effects.Advances in Probiotics for Health and Nutrition; Intechopen, 2024. 
 [http://dx.doi.org/10.5772/intechopen.110725]

[251]
Matsumoto, M.; Inoue, R.; Tsukahara, T.; Ushida, K.; Chiji, H.; Matsubara, N.; Hara, H. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci. Biotechnol. Biochem.,  2008, 72(2), 572-576.
 [http://dx.doi.org/10.1271/bbb.70474] [PMID: 18256465]

[252]
Perrin, P.; Pierre, F.; Patry, Y.; Champ, M.; Berreur, M.; Pradal, G.; Bornet, F.; Meflah, K.; Menanteau, J. Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Gut,  2001, 48(1), 53-61.
 [http://dx.doi.org/10.1136/gut.48.1.53] [PMID: 11115823]

[253]
McNamara, M.P.; Venable, E.M.; Cadney, M.D.; Castro, A.A.; Schmill, M.P.; Kazzazi, L.; Carmody, R.N.; Garland, T., Jr Weanling gut microbiota composition of a mouse model selectively bred for high voluntary wheel-running behavior. J. Exp. Biol.,  2023, 226(4), jeb245081.
 [http://dx.doi.org/10.1242/jeb.245081] [PMID: 36728594]

[254]
Zhang, L.; Wang, Y.; Sun, Y.; Zhang, X. Intermittent fasting and physical exercise for preventing metabolic disorders through interaction with gut microbiota: A review. Nutrients,  2023, 15(10), 2277.
 [http://dx.doi.org/10.3390/nu15102277] [PMID: 37242160]

[255]
Oniszczuk, A.; Oniszczuk, T.; Gancarz, M.; Szymańska, J. Role of gut microbiota, probiotics and prebiotics in the cardiovascular diseases. Molecules,  2021, 26(4), 1172.
 [http://dx.doi.org/10.3390/molecules26041172] [PMID: 33671813]

[256]
Liong, M.T.; Dunshea, F.R.; Shah, N.P. Effects of a synbiotic containing Lactobacillus acidophilus ATCC 4962 on plasma lipid profiles and morphology of erythrocytes in hypercholesterolaemic pigs on high- and low-fat diets. Br. J. Nutr.,  2007, 98(4), 736-744.
 [http://dx.doi.org/10.1017/S0007114507747803] [PMID: 17490507]

[257]
Chi, C.; Li, C.; Wu, D.; Buys, N.; Wang, W.; Fan, H.; Sun, J. Effects of probiotics on patients with hypertension: A systematic review and meta-analysis. Curr. Hypertens. Rep.,  2020, 22(5), 33.
 [http://dx.doi.org/10.1007/s11906-020-01041-5] [PMID: 32200440]

[258]
Shah, B.R.; Li, B.; Al Sabbah, H.; Xu, W.; Mráz, J. Effects of prebiotic dietary fibers and probiotics on human health: With special focus on recent advancement in their encapsulated formulations. Trends Food Sci. Technol.,  2020, 102, 178-192.
 [http://dx.doi.org/10.1016/j.tifs.2020.06.010] [PMID: 32834500]

[259]
Haghighat, N.; Mohammadshahi, M.; Shayanpour, S.; Haghighizadeh, M.H. Effect of synbiotic and probiotic supplementation on serum levels of endothelial cell adhesion molecules in hemodialysis patients: A randomized control study. Probiotics Antimicrob. Proteins,  2019, 11(4), 1210-1218.
 [http://dx.doi.org/10.1007/s12602-018-9477-9] [PMID: 30293208]

[260]
Malik, M.; Suboc, T.M.; Tyagi, S.; Salzman, N.; Wang, J.; Ying, R.; Tanner, M.J.; Kakarla, M.; Baker, J.E.; Widlansky, M.E. Lactobacillus plantarum 299v supplementation improves vascular endothelial function and reduces inflammatory biomarkers in men with stable coronary artery disease. Circ. Res.,  2018, 123(9), 1091-1102.
 [http://dx.doi.org/10.1161/CIRCRESAHA.118.313565] [PMID: 30355158]

[261]
Zhou, X.; Li, J.; Guo, J.; Geng, B.; Ji, W.; Zhao, Q.; Li, J.; Liu, X.; Liu, J.; Guo, Z.; Cai, W.; Ma, Y.; Ren, D.; Miao, J.; Chen, S.; Zhang, Z.; Chen, J.; Zhong, J.; Liu, W.; Zou, M.; Li, Y.; Cai, J. Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction. Microbiome,  2018, 6(1), 66.
 [http://dx.doi.org/10.1186/s40168-018-0441-4] [PMID: 29615110]

[262]
Ponziani, F.R.; Zocco, M.A.; D’Aversa, F.; Pompili, M.; Gasbarrini, A. Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation. World J. Gastroenterol.,  2017, 23(25), 4491-4499.
 [http://dx.doi.org/10.3748/wjg.v23.i25.4491] [PMID: 28740337]

[263]
Conraads, V.M.; Jorens, P.G.; De Clerck, L.S.; Van Saene, H.K.; Ieven, M.M.; Bosmans, J.M.; Schuerwegh, A.; Bridts, C.H.; Wuyts, F.; Stevens, W.J.; Anker, S.D.; Rauchhaus, M.; Vrints, C.J. Selective intestinal decontamination in advanced chronic heart failure: A pilot trial. Eur. J. Heart Fail.,  2004, 6(4), 483-491.
 [http://dx.doi.org/10.1016/j.ejheart.2003.12.004] [PMID: 15182775]

[264]
Chen, K.; Zheng, X.; Feng, M.; Li, D.; Zhang, H. Gut microbiota-dependent metabolite trimethylamine n-oxide contributes to cardiac dysfunction in western diet-induced obese mice. Front. Physiol.,  2017, 8(MAR), 139.
 [http://dx.doi.org/10.3389/fphys.2017.00139] [PMID: 28377725]

[265]
Chen, M.; Yi, L.; Zhang, Y.; Zhou, X.; Ran, L.; Yang, J.; Zhu, J.; Zhang, Q.; Mi, M. Resveratrol attenuates trimethylamine- n -oxide (tmao)-induced atherosclerosis by regulating tmao synthesis and bile acid metabolism via remodeling of the gut microbiota. MBio,  2016, 7(2), e02210-15.
 [http://dx.doi.org/10.1128/mBio.02210-15] [PMID: 27048804]

[266]
Netto Candido, T.L.; Alfenas, R.C.G.; Bressan, J. Dysbiosis and metabolic endotoxemia induced by high-fat diet. Nutr. Hosp.,  2018, 35(6)
 [http://dx.doi.org/10.20960/nh.1792]

[267]
Kopp, W. How western diet and lifestyle drive the pandemic of obesity and civilization diseases. Diabetes Metab. Syndr. Obes.,  2019, 12, 2221-2236.
 [http://dx.doi.org/10.2147/DMSO.S216791] [PMID: 31695465]

[268]
Martínez-González, M.A.; Corella, D.; Salas-Salvadó, J.; Ros, E.; Covas, M.I.; Fiol, M.; Wärnberg, J.; Arós, F.; Ruíz-Gutiérrez, V.; Lamuela-Raventós, R.M.; Lapetra, J.; Muñoz, M.A.; Martínez, J.A.; Sáez, G.; Serra-Majem, L.; Pintó, X.; Mitjavila, M.T.; Tur, J.A.; Portillo, M.P.; Estruch, R. Cohort Profile: Design and methods of the PREDIMED study. Int. J. Epidemiol.,  2012, 41(2), 377-385.
 [http://dx.doi.org/10.1093/ije/dyq250] [PMID: 21172932]

[269]
Berger, S.; Raman, G.; Vishwanathan, R.; Jacques, P.F.; Johnson, E.J. Dietary cholesterol and cardiovascular disease: A systematic review and meta-analysis. Am. J. Clin. Nutr.,  2015, 102(2), 276-294.
 [http://dx.doi.org/10.3945/ajcn.114.100305] [PMID: 26109578]

[270]
Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.; Muccioli, G.G.; Delzenne, N.M.; de Vos, W.M.; Cani, P.D. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci.,  2013, 110(22), 9066-9071.
 [http://dx.doi.org/10.1073/pnas.1219451110] [PMID: 23671105]

[271]
Wilck, N.; Matus, M.G.; Kearney, S.M.; Olesen, S.W.; Forslund, K.; Bartolomaeus, H.; Haase, S.; Mähler, A.; Balogh, A.; Markó, L.; Vvedenskaya, O.; Kleiner, F.H.; Tsvetkov, D.; Klug, L.; Costea, P.I.; Sunagawa, S.; Maier, L.; Rakova, N.; Schatz, V.; Neubert, P.; Frätzer, C.; Krannich, A.; Gollasch, M.; Grohme, D.A.; Côrte-Real, B.F.; Gerlach, R.G.; Basic, M.; Typas, A.; Wu, C.; Titze, J.M.; Jantsch, J.; Boschmann, M.; Dechend, R.; Kleinewietfeld, M.; Kempa, S.; Bork, P.; Linker, R.A.; Alm, E.J.; Müller, D.N. Salt-responsive gut commensal modulates TH17 axis and disease. Nature,  2017, 551(7682), 585-589.
 [http://dx.doi.org/10.1038/nature24628] [PMID: 29143823]

[272]
Krznarić, Ž.; Vranešić Bender, D.; Meštrović, T. The Mediterranean diet and its association with selected gut bacteria. Curr. Opin. Clin. Nutr. Metab. Care,  2019, 22(5), 401-406.
 [http://dx.doi.org/10.1097/MCO.0000000000000587] [PMID: 31232713]

[273]
Garcia-Mantrana, I.; Selma-Royo, M.; Alcantara, C.; Collado, M.C. Shifts on gut microbiota associated to mediterranean diet adherence and specific dietary intakes on general adult population. Front. Microbiol.,  2018, 9, 890.
 [http://dx.doi.org/10.3389/fmicb.2018.00890] [PMID: 29867803]

[274]
Yu, E.W.; Gao, L.; Stastka, P.; Cheney, M.C.; Mahabamunuge, J.; Torres Soto, M.; Ford, C.B.; Bryant, J.A.; Henn, M.R.; Hohmann, E.L. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PLoS Med.,  2020, 17(3), e1003051.
 [http://dx.doi.org/10.1371/journal.pmed.1003051] [PMID: 32150549]

[275]
De Groot, P.; Scheithauer, T.; Bakker, G.J.; Prodan, A.; Levin, E.; Khan, M.T.; Herrema, H.; Ackermans, M.; Serlie, M.J.M.; De Brauw, M.; Levels, J.H.M.; Sales, A.; Gerdes, V.E.; Ståhlman, M.; Schimmel, A.W.M.; Dallinga-Thie, G.; Bergman, J.J.; Holleman, F.; Hoekstra, J.B.L.; Groen, A.; Bäckhed, F.; Nieuwdorp, M. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut,  2020, 69(3), 502-512.
 [http://dx.doi.org/10.1136/gutjnl-2019-318320] [PMID: 31147381]

[276]
Wang, H.; Lu, Y.; Yan, Y.; Tian, S.; Zheng, D.; Leng, D.; Wang, C.; Jiao, J.; Wang, Z.; Bai, Y. Promising treatment for type 2 diabetes: Fecal microbiota transplantation reverses insulin resistance and impaired islets. Front. Cell. Infect. Microbiol.,  2020, 9, 455.
 [http://dx.doi.org/10.3389/fcimb.2019.00455] [PMID: 32010641]

[277]
Hu, X.F.; Zhang, W.Y.; Wen, Q.; Chen, W.J.; Wang, Z.M.; Chen, J.; Zhu, F.; Liu, K.; Cheng, L.X.; Yang, J.; Shu, Y.W. Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition. Pharmacol. Res.,  2019, 139, 412-421.
 [http://dx.doi.org/10.1016/j.phrs.2018.11.042] [PMID: 30508676]

[278]
Toral, M.; Robles-Vera, I.; de la Visitación, N.; Romero, M.; Yang, T.; Sánchez, M.; Gómez-Guzmán, M.; Jiménez, R.; Raizada, M.K.; Duarte, J. Critical role of the interaction gut microbiota – sympathetic nervous system in the regulation of blood pressure. Front. Physiol.,  2019, 10, 231.
 [http://dx.doi.org/10.3389/fphys.2019.00231] [PMID: 30930793]

[279]
Smits, L.P.; Kootte, R.S.; Levin, E.; Prodan, A.; Fuentes, S.; Zoetendal, E.G.; Wang, Z.; Levison, B.S.; Cleophas, M.C.P.; Kemper, E.M.; Dallinga-Thie, G.M.; Groen, A.K.; Joosten, L.A.B.; Netea, M.G.; Stroes, E.S.G.; de Vos, W.M.; Hazen, S.L.; Nieuwdorp, M. Effect of vegan fecal microbiota transplantation on carnitine‐ and choline‐derived trimethylamine‐n‐oxide production and vascular inflammation in patients with metabolic syndrome. J. Am. Heart Assoc.,  2018, 7(7), e008342.
 [http://dx.doi.org/10.1161/JAHA.117.008342] [PMID: 29581220]

[280]
Shih, D.M.; Zhu, W.; Schugar, R.C.; Meng, Y.; Jia, X.; Miikeda, A.; Wang, Z.; Zieger, M.; Lee, R.; Graham, M.; Allayee, H.; Cantor, R.M.; Mueller, C.; Brown, J.M.; Hazen, S.L.; Lusis, A.J. Genetic deficiency of flavin-containing monooxygenase 3 fmo3 protects against thrombosis but has only a minor effect on plasma lipid levels—brief report. Arterioscler. Thromb. Vasc. Biol.,  2019, 39(6), 1045-1054.
 [http://dx.doi.org/10.1161/ATVBAHA.119.312592] [PMID: 31070450]

[281]
Papi, M.; Caracciolo, G. Principal component analysis of personalized biomolecular corona data for early disease detection. Nano Today,  2018, 21, 14-17.
 [http://dx.doi.org/10.1016/j.nantod.2018.03.001]

[282]
Caracciolo, G.; Safavi-Sohi, R.; Malekzadeh, R.; Poustchi, H.; Vasighi, M.; Zenezini Chiozzi, R.; Capriotti, A.L.; Laganà, A.; Hajipour, M.; Di Domenico, M.; Di Carlo, A.; Caputo, D.; Aghaverdi, H.; Papi, M.; Palmieri, V.; Santoni, A.; Palchetti, S.; Digiacomo, L.; Pozzi, D.; Suslick, K.S.; Mahmoudi, M. Disease-specific protein corona sensor arrays may have disease detection capacity. Nanoscale Horiz.,  2019, 4(5), 1063-1076.
 [http://dx.doi.org/10.1039/C9NH00097F]

[283]
Ashkarran, A.A.; Olfatbakhsh, T.; Ramezankhani, M.; Crist, R.C.; Berrettini, W.H.; Milani, A.S.; Pakpour, S.; Mahmoudi, M. Evolving magnetically levitated plasma proteins detects opioid use disorder as a model disease. Adv. Healthc. Mater.,  2020, 9(5), 1901608.
 [http://dx.doi.org/10.1002/adhm.201901608] [PMID: 31994348]

[284]
Topol, E.J. High-performance medicine: the convergence of human and artificial intelligence. Nat. Med.,  2019, 25(1), 44-56.
 [http://dx.doi.org/10.1038/s41591-018-0300-7] [PMID: 30617339]

[285]
Aryal, S.; Alimadadi, A.; Manandhar, I.; Joe, B.; Cheng, X. Machine learning strategy for gut microbiome-based diagnostic screening of cardiovascular disease. Hypertension,  2020, 76(5), 1555-1562.
 [http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15885] [PMID: 32909848]

[286]
Gibson, P.R.; Shepherd, S.J. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J. Gastroenterol. Hepatol.,  2010, 25(2), 252-258.

[287]
Wang, L.; Alammar, N.; Singh, R.; Nanavati, J.; Song, Y.; Chaudhary, R.; Mullin, G.E. Gut microbial dysbiosis in the irritable bowel syndrome: A systematic review and meta-analysis of case-control studies. J. Acad. Nutr. Diet.,  2020, 120(4), 565-586.
 [http://dx.doi.org/10.1016/j.jand.2019.05.015] [PMID: 31473156]

[288]
Altobelli, E.; Del Negro, V.; Angeletti, P.; Latella, G. Low-FODMAP diet improves irritable bowel syndrome symptoms: A meta-analysis. Nutrients,  2017, 9(9), 940.
 [http://dx.doi.org/10.3390/nu9090940] [PMID: 28846594]

[289]
Halmos, E.P.; Power, V.A.; Shepherd, S.J.; Gibson, P.R.; Muir, J.G. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology,  2014, 146(1), 67-75.
 [http://dx.doi.org/10.1053/j.gastro.2013.09.046] [PMID: 24076059]

[290]
Biesiekierski, J.R.; Peters, S.L.; Newnham, E.D.; Rosella, O.; Muir, J.G.; Gibson, P.R. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology,  2013, 145(2), 320-328.e3, 3.
 [http://dx.doi.org/10.1053/j.gastro.2013.04.051] [PMID: 23648697]

[291]
Bennett, B.J.; Davis, R.C.; Civelek, M.; Orozco, L.; Wu, J.; Qi, H.; Pan, C.; Packard, R.R.S.; Eskin, E.; Yan, M.; Kirchgessner, T.; Wang, Z.; Li, X.; Gregory, J.C.; Hazen, S.L.; Gargalovic, P.S.; Lusis, A.J. Genetic architecture of atherosclerosis in mice: A systems genetics analysis of common inbred strains. PLoS Genet.,  2015, 11(12), e1005711.
 [http://dx.doi.org/10.1371/journal.pgen.1005711] [PMID: 26694027]

[292]
Warrier, M.; Shih, D.M.; Burrows, A.C.; Ferguson, D.; Gromovsky, A.D.; Brown, A.L.; Marshall, S.; McDaniel, A.; Schugar, R.C.; Wang, Z.; Sacks, J.; Rong, X.; Vallim, T.A.; Chou, J.; Ivanova, P.T.; Myers, D.S.; Brown, H.A.; Lee, R.G.; Crooke, R.M.; Graham, M.J.; Liu, X.; Parini, P.; Tontonoz, P.; Lusis, A.J.; Hazen, S.L.; Temel, R.E.; Brown, J.M. The TMAO-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance. Cell Rep.,  2015, 10(3), 326-338.
 [http://dx.doi.org/10.1016/j.celrep.2014.12.036] [PMID: 25600868]

[293]
Miao, J.; Ling, A.V.; Manthena, P.V.; Gearing, M.E.; Graham, M.J.; Crooke, R.M.; Croce, K.J.; Esquejo, R.M.; Clish, C.B.; Torrecilla, E.; Vázquez, G.F.; Rubio, M.A.; Cabrerizo, L.; Barabash, A.; Pernaute, A.S.; Torres, A.J.; Vicent, D.; Biddinger, S.B. Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat. Commun.,  2015, 6(1), 6498.
 [http://dx.doi.org/10.1038/ncomms7498] [PMID: 25849138]

[294]
Shih, D.M.; Wang, Z.; Lee, R.; Meng, Y.; Che, N.; Charugundla, S.; Qi, H.; Wu, J.; Pan, C.; Brown, J.M.; Vallim, T.; Bennett, B.J.; Graham, M.; Hazen, S.L.; Lusis, A.J. Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis. J. Lipid Res.,  2015, 56(1), 22-37.
 [http://dx.doi.org/10.1194/jlr.M051680] [PMID: 25378658]

[295]
Wang, Z.; Roberts, A.B.; Buffa, J.A.; Levison, B.S.; Zhu, W.; Org, E.; Gu, X.; Huang, Y.; Zamanian-Daryoush, M.; Culley, M.K.; DiDonato, A.J.; Fu, X.; Hazen, J.E.; Krajcik, D.; DiDonato, J.A.; Lusis, A.J.; Hazen, S.L. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell,  2015, 163(7), 1585-1595.
 [http://dx.doi.org/10.1016/j.cell.2015.11.055] [PMID: 26687352]
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DOI https://dx.doi.org/10.2174/011871529X310857240607103028	Print ISSN 1871-529X
Publisher Name Bentham Science Publisher	Online ISSN 2212-4063
Cardiovascular & Hematological Disorders-Drug Targets

Mechanistic Review on the Role of Gut Microbiota in the Pathology of Cardiovascular Diseases

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