{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T19:45:10Z","timestamp":1784835910003,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The role of the gut microbiome (GM) and oral microbiome (OM) in cardiovascular disease (CVD) has been increasingly being understood in recent years. It is well known that GM is a risk factor for various CVD phenotypes, including hypertension, dyslipidemia, heart failure and atrial fibrillation. However, its role in valvular heart disease (VHD) is less well understood. Research shows that, direct, microbe-mediated and indirect, metabolite-mediated damage as a result of gut dysbiosis and environmental factors results in a subclinical, chronic, systemic inflammatory state, which promotes inflammatory cell infiltration in heart valves and subsequently, via pro-inflammatory molecules, initiates a cascade of reaction, resulting in valve calcification, fibrosis and dysfunction. This relationship between GM and VHD adds a pathophysiological link to the pathogenesis of VHD, which can be aimed therapeutically, in order to prevent or regress any risk for valvular pathologies. Therapeutic interventions include dietary modifications and lifestyle interventions, in order to influence environmental factors that can promote gut dysbiosis. Furthermore, the combination of probiotics and prebiotics, as well as fecal m transplantation and targeted treatment with inducers or inhibitors of microbial enzymes have showed promising results in animal and\/or clinical studies, with the potential to reduce the inflammatory state and restore the normal gut flora in patients. This review, thus, is going to discuss the pathophysiological links behind the relationship of GM, CVD and VHD, as well as explore the recent data regarding the effect of GM-altering treatment in CVD, cardiac function and systemic inflammation.<\/jats:p>","DOI":"10.3390\/life14040527","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T10:53:17Z","timestamp":1713523997000},"page":"527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut Microbiome and Its Role in Valvular Heart Disease: Not a \u201cGutted\u201d Relationship"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-7163","authenticated-orcid":false,"given":"Gyanaranjan","family":"Nayak","sequence":"first","affiliation":[{"name":"First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0401-9473","authenticated-orcid":false,"given":"Nikolaos","family":"Pyrpyris","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-9086","authenticated-orcid":false,"given":"Magdalini","family":"Manti","sequence":"additional","affiliation":[{"name":"St Mark\u2019s Hospital, Imperial College London, London HA1 3UJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Kamperidis","sequence":"additional","affiliation":[{"name":"St Mark\u2019s Hospital, Imperial College London, London HA1 3UJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-6718","authenticated-orcid":false,"given":"Vasileios","family":"Kamperidis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54453 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios","family":"Ziakas","sequence":"additional","affiliation":[{"name":"First Cardiology Department, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, 54453 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tsioufis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Amini, M., Zayeri, F., and Salehi, M. (2021). Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: Results from global burden of disease study 2017. BMC Public Health, 21.","DOI":"10.1186\/s12889-021-10429-0"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Karlsson, F.H., F\u00e5k, F., Nookaew, I., Tremaroli, V., Fagerberg, B., Petranovic, D., B\u00e4ckhed, F., and Nielsen, J. (2012). Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun., 3.","DOI":"10.1038\/ncomms2266"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yamashiro, K., Tanaka, R., Urabe, T., Ueno, Y., Yamashiro, Y., Nomoto, K., Takahashi, T., Tsuji, H., Asahara, T., and Hattori, N. (2017). Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176062"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the human gut microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s11154-019-09526-8","article-title":"Oral microbiota-induced periodontitis: A new risk factor of metabolic diseases","volume":"20","author":"Minty","year":"2019","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S1473-3099(15)00293-5","article-title":"A comprehensive repertoire of prokaryotic species identified in human beings","volume":"15","author":"Hugon","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Panzer, J.J., Romero, R., Greenberg, J.M., Winters, A.D., Galaz, J., Gomez-Lopez, N., and Theis, K.R. (2023). Is there a placental microbiota? A critical review and re-analysis of published placental microbiota datasets. BMC Microbiol., 23.","DOI":"10.1186\/s12866-023-02764-6"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Stinson, L., Hallingstr\u00f6m, M., Barman, M., Viklund, F., Keelan, J., Kacerovsky, M., Payne, M., and Jacobsson, B. (2020). Comparison of Bacterial DNA Profiles in Mid-Trimester Amniotic Fluid Samples From Preterm and Term Deliveries. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00415"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Miko, E., Csaszar, A., Bodis, J., and Kovacs, K. (2022). The Maternal\u2013Fetal Gut Microbiota Axis: Physiological Changes, Dietary Influence, and Modulation Possibilities. Life, 12.","DOI":"10.3390\/life12030424"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, J.M., Murphy, K., Stanton, C., Ross, R.P., Kober, O.I., Juge, N., Avershina, E., Rudi, K., Narbad, A., and Jenmalm, M.C. (2015). The composition of the gut microbiota throughout life, with an emphasis on early life. Microb. Ecol. Health Dis., 26.","DOI":"10.3402\/mehd.v26.26050"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jandhyala, S.M. (2015). Role of the normal gut microbiota. World J. Gastroenterol., 21.","DOI":"10.3748\/wjg.v21.i29.8787"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Corr\u00eaa-Oliveira, R., Fachi, J.L., Vieira, A., Sato, F.T., and Vinolo, M.A.R. (2016). Regulation of immune cell function by short-chain fatty acids. Clin. Transl. Immunol., 5.","DOI":"10.1038\/cti.2016.17"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phrs.2012.10.007","article-title":"Modulation of intestinal barrier by intestinal microbiota: Pathological and therapeutic implications","volume":"69","author":"Natividad","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/19490976.2015.1056973","article-title":"A commensal symbiotic factor derived from Bacteroides fragilis promotes human CD39+ Foxp3+ T cells and Treg function","volume":"6","author":"Telesford","year":"2015","journal-title":"Gut Microbes"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mousa, W.K., Chehadeh, F., and Husband, S. (2022). Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.906258"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1042\/CS20200475","article-title":"Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis","volume":"134","author":"Su","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Din, A.U., Mazhar, M., Waseem, M., Ahmad, W., Bibi, A., Hassan, A., Ali, N., Gang, W., Qian, G., and Ullah, R. (2021). SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role. Biomed. Pharmacother., 133.","DOI":"10.1016\/j.biopha.2020.110947"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lau, K., Srivatsav, V., Rizwan, A., Nashed, A., Liu, R., Shen, R., and Akhtar, M. (2017). Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients, 9.","DOI":"10.3390\/nu9080859"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"C448","DOI":"10.1152\/ajpcell.00295.2020","article-title":"LPS-induced epithelial barrier disruption via hyperactivation of CACC and ENaC","volume":"320","author":"Kim","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1042\/CS20180087","article-title":"Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure","volume":"132","author":"Kim","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41569-022-00737-2","article-title":"Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease","volume":"20","author":"Violi","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_23","first-page":"1187","article-title":"Bacterial lipopolysaccharide and antimicrobial LL-37 enhance ICAM-1 expression and NF-\u03baB p65 phosphorylation in senescent endothelial cells","volume":"44","author":"Suzuki","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.tcm.2021.08.015","article-title":"Implications for the role of lipopolysaccharide in the development of atherosclerosis","volume":"32","author":"Gorabi","year":"2022","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pastori, D., Carnevale, R., Nocella, C., Novo, M., Santulli, M., Cammisotto, V., Menichelli, D., Pignatelli, P., and Violi, F. (2017). 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., 6.","DOI":"10.1161\/JAHA.117.005784"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ijcard.2006.03.003","article-title":"Endotoxin hypersensitivity in chronic heart failure","volume":"115","author":"Kunz","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1161\/ATVBAHA.112.249847","article-title":"Toll-Like Receptor 4 Deficiency Decreases Atherosclerosis but Does Not Protect Against Inflammation in Obese Low-Density Lipoprotein Receptor\u2013Deficient Mice","volume":"32","author":"Ding","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Seldin, M.M., Meng, Y., Qi, H., Zhu, W., Wang, Z., Hazen, S.L., Lusis, A.J., and Shih, D.M. (2016). Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-\u03baB. J. Am. Heart Assoc., 5.","DOI":"10.1161\/JAHA.115.002767"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jing, L., Zhang, H., Xiang, Q., Shen, L., Guo, X., Zhai, C., and Hu, H. (2022). Targeting Trimethylamine N-Oxide: A New Therapeutic Strategy for Alleviating Atherosclerosis. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.864600"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xie, Z., Liu, X., Huang, X., Liu, Q., Yang, M., Huang, D., Zhao, P., Tian, J., Wang, X., and Hou, J. (2021). Remodelling of gut microbiota by Berberine attenuates trimethylamine N-oxide-induced platelet hyperreaction and thrombus formation. Eur. J. Pharmacol., 911.","DOI":"10.1016\/j.ejphar.2021.174526"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zong, X., Fan, Q., Yang, Q., Pan, R., Zhuang, L., Xi, R., Zhang, R., and Tao, R. (2022). Trimethyllysine, a trimethylamine N-oxide precursor, predicts the presence, severity, and prognosis of heart failure. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.907997"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.yjmcc.2019.07.004","article-title":"Gut microbe-derived metabolite trimethylamine N-oxide accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis","volume":"134","author":"Yang","year":"2019","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Organ, C.L., Otsuka, H., Bhushan, S., Wang, Z., Bradley, J., Trivedi, R., Polhemus, D.J., Tang, W.H., Wu, Y., and Hazen, S.L. (2016). Choline Diet and Its Gut Microbe\u2013Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload\u2013Induced Heart Failure. Circ. Heart Fail., 9.","DOI":"10.1161\/CIRCHEARTFAILURE.115.002314"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Organ, C.L., Li, Z., Sharp, T.E., Polhemus, D.J., Gupta, N., Goodchild, T.T., Tang, W.H.W., Hazen, S.L., and Lefer, D.J. (2020). 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., 9.","DOI":"10.1161\/JAHA.119.016223"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1161\/ATVBAHA.120.314139","article-title":"Targeted Inhibition of Gut Microbial Trimethylamine N-Oxide Production Reduces Renal Tubulointerstitial Fibrosis and Functional Impairment in a Murine Model of Chronic Kidney Disease","volume":"40","author":"Gupta","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhao, P., Zhao, S., Tian, J., and Liu, X. (2022). Significance of Gut Microbiota and Short-Chain Fatty Acids in Heart Failure. Nutrients, 14.","DOI":"10.3390\/nu14183758"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.atherosclerosis.2021.08.029","article-title":"Phenylacetylglutamine is associated with the degree of coronary atherosclerotic severity assessed by coronary computed tomographic angiography in patients with suspected coronary artery disease","volume":"333","author":"Liu","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pcad.2023.06.002","article-title":"The common pathobiology between coronary artery disease and calcific aortic stenosis: Evidence and clinical implications","volume":"79","author":"Garg","year":"2023","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.15698\/mic2023.02.791","article-title":"The first taxonomic and functional characterization of human CAVD-associated microbiota","volume":"10","author":"Curini","year":"2023","journal-title":"Microb. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"H141","DOI":"10.1152\/ajpheart.00100.2019","article-title":"Adaptive immune cells in calcific aortic valve disease","volume":"317","author":"Raddatz","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1080\/00015385.2020.1853968","article-title":"Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis","volume":"76","author":"Kocyigit","year":"2021","journal-title":"Acta Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jing, W., Huang, S., Xiang, P., Huang, J., and Yu, H. (2023). Dietary precursors and cardiovascular disease: A Mendelian randomization study. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1061119"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Guo, Y., Xu, S., Zhan, H., Chen, H., Hu, P., Zhou, D., Dai, H., Liu, X., Hu, W., and Zhu, G. (2023). Trimethylamine N-Oxide Levels Are Associated with Severe Aortic Stenosis and Predict Long-Term Adverse Outcome. J. Clin. Med., 12.","DOI":"10.3390\/jcm12020407"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Xiong, Z., Li, J., Huang, R., Zhou, H., Xu, X., Zhang, S., Xie, P., Li, M., Guo, Y., and Liao, X. (2024). The gut microbe-derived metabolite trimethylamine-N-oxide induces aortic valve fibrosis via PERK\/ATF-4 and IRE-1\u03b1\/XBP-1s signaling in vitro and in vivo. Atherosclerosis, 391.","DOI":"10.1016\/j.atherosclerosis.2023.117431"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.atherosclerosis.2018.11.038","article-title":"The intestinal microbiota associated with cardiac valve calcification differs from that of coronary artery disease","volume":"284","author":"Liu","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/jcpe.13189","article-title":"Periodontitis and cardiovascular diseases: Consensus report","volume":"47","author":"Sanz","year":"2020","journal-title":"J. Clin. Periodontol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zardawi, F., Gul, S., Abdulkareem, A., Sha, A., and Yates, J. (2021). Association Between Periodontal Disease and Atherosclerotic Cardiovascular Diseases: Revisited. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.625579"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1902\/jop.2000.71.10.1554","article-title":"Identification of Periodontal Pathogens in Atheromatous Plaques","volume":"71","author":"Haraszthy","year":"2000","journal-title":"J. Periodontol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"E15","DOI":"10.1161\/CIRCRESAHA.119.315502","article-title":"BMAL1-Downregulation Aggravates Porphyromonas Gingivalis-Induced Atherosclerosis by Encouraging Oxidative Stress","volume":"126","author":"Xie","year":"2020","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Seoane, T., Bullon, B., Fernandez-Riejos, P., Garcia-Rubira, J.C., Garcia-Gonzalez, N., Villar-Calle, P., Quiles, J.L., Battino, M., and Bullon, P. (2022). Periodontitis and Other Risk Factors Related to Myocardial Infarction and Its Follow-Up. J. Clin. Med., 11.","DOI":"10.3390\/jcm11092618"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1399-302X.2008.00479.x","article-title":"Detection of oral bacteria in cardiovascular specimens","volume":"24","author":"Nakano","year":"2009","journal-title":"Oral. Microbiol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Oliveira, F.A.F., Forte, C.P.F., Silva, P.G.d.B., Lopes, C.B., Montenegro, R.C., Santos, \u00c2.K.C.R.D., Sobrinho, C.R.M.R., Mota, M.R.L., Sousa, F.B., and Alves, A.P.N.N. (2015). Molecular Analysis of Oral Bacteria in Heart Valve of Patients With Cardiovascular Disease by Real-Time Polymerase Chain Reaction. Medicine, 94.","DOI":"10.1097\/MD.0000000000002067"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/jcpe.13478","article-title":"Periodontitis is associated with incidental valvular heart disease: A nationwide population-based cohort study","volume":"48","author":"Sia","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Aardema, H., Lisotto, P., Kurilshikov, A., Diepeveen, J.R.J., Friedrich, A.W., Sinha, B., de Smet, A.M.G.A., and Harmsen, H.J.M. (2020). Marked Changes in Gut Microbiota in Cardio-Surgical Intensive Care Patients: A Longitudinal Cohort Study. Front. Cell Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00467"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Xue, L., Ding, Y., Qin, Q., Liu, L., Ding, X., Zhou, Y., Liu, K., Singla, R.K., Shen, K., and Din, A.U. (2023). Assessment of the impact of intravenous antibiotics treatment on gut microbiota in patients: Clinical data from pre-and post-cardiac surgery. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1043971"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3945\/ajcn.115.109496","article-title":"Fecal menaquinone profiles of overweight adults are associated with gut microbiota composition during a gut microbiota\u2013targeted dietary intervention","volume":"102","author":"Karl","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chen, W., Qian, J., Fu, J., Wu, T., Lv, M., Jiang, S., and Zhang, J. (2022). Changes in the Gut Microbiota May Affect the Clinical Efficacy of Oral Anticoagulants. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.860237"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature12820","article-title":"Diet rapidly and reproducibly alters the human gut microbiome","volume":"505","author":"David","year":"2014","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.2337\/db07-1403","article-title":"Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet\u2013Induced Obesity and Diabetes in Mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Agans, R., Gordon, A., Kramer, D.L., Perez-Burillo, S., Rufi\u00e1n-Henares, J.A., and Paliy, O. (2018). Dietary Fatty Acids Sustain the Growth of the Human Gut Microbiota. Appl. Environ. Microbiol., 84.","DOI":"10.1128\/AEM.01525-18"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2018.05.012","article-title":"The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease","volume":"23","author":"Makki","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Barber, T.M., Kabisch, S., Pfeiffer, A.F.H., and Weickert, M.O. (2023). The Effects of the Mediterranean Diet on Health and Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15092150"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Merra, G., Noce, A., Marrone, G., Cintoni, M., Tarsitano, M.G., Capacci, A., and De Lorenzo, A. (2020). Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients, 13.","DOI":"10.3390\/nu13010007"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/S0140-6736(22)00122-2","article-title":"Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): A randomised controlled trial","volume":"399","author":"Fuentes","year":"2022","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.echo.2021.06.009","article-title":"Aging Athlete\u2019s Heart: An Echocardiographic Evaluation of Competitive Sprint- versus Endurance-Trained Master Athletes","volume":"34","author":"Kusy","year":"2021","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Martinon, P., Fraticelli, L., Giboreau, A., Dussart, C., Bourgeois, D., and Carrouel, F. (2021). Nutrition as a Key Modifiable Factor for Periodontitis and Main Chronic Diseases. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020197"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Woelber, J.P., Bremer, K., Vach, K., K\u00f6nig, D., Hellwig, E., Ratka-Kr\u00fcger, P., Al-Ahmad, A., and Tennert, C. (2017). An oral health optimized diet can reduce gingival and periodontal inflammation in humans\u2014A randomized controlled pilot study. BMC Oral Health, 17.","DOI":"10.1186\/s12903-016-0257-1"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Altun, E., Walther, C., Borof, K., Petersen, E., Lieske, B., Kasapoudis, D., Jalilvand, N., Beikler, T., Jagemann, B., and Zyriax, B.C. (2021). Association between Dietary Pattern and Periodontitis\u2014A Cross-Sectional Study. Nutrients, 13.","DOI":"10.3390\/nu13114167"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/idj.12317","article-title":"The association between oral hygiene and periodontitis: A systematic review and meta-analysis","volume":"67","author":"Lertpimonchai","year":"2017","journal-title":"Int. Dent. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41430-018-0135-9","article-title":"A review of probiotic supplementation in healthy adults: Helpful or hype?","volume":"73","author":"Khalesi","year":"2019","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1007\/s13197-015-1921-1","article-title":"Probiotics, prebiotics and synbiotics\u2014A review","volume":"52","author":"Pandey","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/CIRCRESAHA.118.313565","article-title":"Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease","volume":"123","author":"Malik","year":"2018","journal-title":"Circ. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1080\/1028415X.2021.1889451","article-title":"The effects of co-administration of probiotics and prebiotics on chronic inflammation, and depression symptoms in patients with coronary artery diseases: A randomized clinical trial","volume":"25","author":"Moludi","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s12265-020-10052-1","article-title":"Probiotics Supplementation on Cardiac Remodeling Following Myocardial Infarction: A Single-Center Double-Blind Clinical Study","volume":"14","author":"Moludi","year":"2021","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ahmadian, F., Razmpoosh, E., Ejtahed, H.S., Javadi, M., Mirmiran, P., and Azizi, F. (2022). Effects of probiotic supplementation on major cardiovascular-related parameters in patients with type-2 diabetes mellitus: A secondary-data analysis of a randomized double-blind controlled trial. Diabetol. Metab. Syndr., 14.","DOI":"10.1186\/s13098-022-00822-z"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10517-020-04726-8","article-title":"Effect of Prebiotic Complex on Gut Microbiota and Endotoxemia in Female Rats with Modeled Heart Failure","volume":"168","author":"Vlasov","year":"2020","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s12602-017-9343-1","article-title":"The Effects of Synbiotic Supplementation on Carotid Intima-Media Thickness, Biomarkers of Inflammation, and Oxidative Stress in People with Overweight, Diabetes, and Coronary Heart Disease: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"11","author":"Farrokhian","year":"2019","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1055\/s-0042-105441","article-title":"A Randomized Controlled Clinical Trial Investigating the Effect of Synbiotic Administration on Markers of Insulin Metabolism and Lipid Profiles in Overweight Type 2 Diabetic Patients with Coronary Heart Disease","volume":"125","author":"Sharifi","year":"2017","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/fsn3.3835","article-title":"Prebiotics Plus Probiotics May Favorably Impact on Gut Permeability, Endocannabinoid Receptors, and Inflammatory Biomarkers in Patients with Coronary Artery Diseases: A Clinical Trial","volume":"12","author":"Liu","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Awoyemi, A., Mayerhofer, C., Felix, A.S., Hov, J.R., Moscavitch, S.D., Lappeg\u00e5rd, K.T., Hovland, A., Halvorsen, S., Halvorsen, B., and Gregersen, I. (2021). Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial. EBioMedicine, 70.","DOI":"10.1016\/j.ebiom.2021.103511"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Loosen, S.H., Krieg, S., Gaensbacher, J., Doege, C., Krieg, A., Luedde, T., Luedde, M., Roderburg, C., and Kostev, K. (2023). The Association between Antibiotic Use and the Incidence of Heart Failure: A Retrospective Case-Control Study of 162,188 Outpatients. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020260"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/1756283X15607414","article-title":"Fecal microbiota transplantation: In perspective","volume":"9","author":"Gupta","year":"2016","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1056\/NEJMoa1205037","article-title":"Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile","volume":"368","author":"Vrieze","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1093\/ecco-jcc\/jjx063","article-title":"Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis","volume":"11","author":"Paramsothy","year":"2017","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1074\/jbc.M114.618249","article-title":"Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation","volume":"290","author":"Gregory","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_86","first-page":"779","article-title":"Reductions in gut microbiota-derived metabolite trimethylamine N-oxide in the circulation may ameliorate myocardial infarction-induced heart failure in rats, possibly by inhibiting interleukin-8 secretion","volume":"20","author":"Li","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Wang, G., Kong, B., Shuai, W., Fu, H., Jiang, X., and Huang, H. (2020). 3,3-Dimethyl-1-butanol attenuates cardiac remodeling in pressure-overload-induced heart failure mice. J. Nutr. Biochem., 78.","DOI":"10.1016\/j.jnutbio.2020.108341"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zou, D., Li, Y., and Sun, G. (2021). Attenuation of Circulating Trimethylamine N-Oxide Prevents the Progression of Cardiac and Renal Dysfunction in a Rat Model of Chronic Cardiorenal Syndrome. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.751380"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1113\/JP283581","article-title":"Initiation of 3,3-dimethyl-1-butanol at midlife prevents endothelial dysfunction and attenuates in vivo aortic stiffening with ageing in mice","volume":"600","author":"Casso","year":"2022","journal-title":"J. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1038\/s41396-022-01240-9","article-title":"Catestatin selects for colonization of antimicrobial-resistant gut bacterial communities","volume":"16","author":"Schwalbe","year":"2022","journal-title":"ISME J."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Wo\u0142owiec, \u0141., Banach, J., Budzy\u0144ski, J., Wo\u0142owiec, A., Kozakiewicz, M., Bieli\u0144ski, M., Ja\u015bniak, A., Olejarczyk, A., and Grze\u015bk, G. (2023). Prognostic Value of Plasma Catestatin Concentration in Patients with Heart Failure with Reduced Ejection Fraction in Two-Year Follow-Up. J. Clin. Med., 12.","DOI":"10.3390\/jcm12134208"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.athoracsur.2020.09.002","article-title":"STS-ACC TVT Registry of Transcatheter Aortic Valve Replacement","volume":"111","author":"Carroll","year":"2021","journal-title":"Ann. Thorac. Surg."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/4\/527\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:31:16Z","timestamp":1760106676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/4\/527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,19]]},"references-count":92,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["life14040527"],"URL":"https:\/\/doi.org\/10.3390\/life14040527","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,19]]}}}