{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:51:38Z","timestamp":1791910298485,"version":"4.3.4"},"reference-count":113,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss National Science Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"Swiss National Science Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"Swiss Heart Foundation and the Lindenberg Family Office","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"Swiss Heart Foundation and the Lindenberg Family Office","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"H.H. Sheikh Khalifa bin Hamad Al-Thani to the University of Zurich, Switzerland","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"H.H. Sheikh Khalifa bin Hamad Al-Thani to the University of Zurich, Switzerland","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"OPO Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"OPO Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"the Iten-Kohaut Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"the Iten-Kohaut Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"Boston Scientific","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"Boston Scientific","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"Edwards Lifesciences","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"Edwards Lifesciences","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"InnoSuisse\u2014Swiss Innovation Agency","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"InnoSuisse\u2014Swiss Innovation Agency","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"Swiss Cancer Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"Swiss Cancer Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"Swiss National Science Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"Swiss National Science Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"ISREC Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"ISREC Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"EoE Foundation","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"EoE Foundation","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]},{"name":"the Comprehensive Cancer Center Zurich","award":["310030-146923"],"award-info":[{"award-number":["310030-146923"]}]},{"name":"the Comprehensive Cancer Center Zurich","award":["310030-165990"],"award-info":[{"award-number":["310030-165990"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent reports demonstrate an association between distinct bacteria or bacteria-derived metabolites originating from the gut microbiome and the onset or progression of cardiovascular disease (CVD). This raises the opportunity to modulate the gut microbiome to prevent or treat CVD. To investigate whether intestinal microbiome modulation can prevent or treat CVD, this systematic literature review includes all randomized clinical trials on microbiome modulation and its effects on CVD risk published between August 2018 and August 2023. Within this review, we report the modulation of the gut microbiome by a variety of interventions and their effects on CVD, focusing on cardiovascular risk factors and risk markers of CVD. Beneficial effects were observed upon lifestyle intervention and probiotics use. The most promising diets for reducing risk factors of CVD were the Mediterranean diet, high-fiber diets, polyphenol-rich diets, and diets containing polyunsaturated fatty acids. Among drug interventions, only empagliflozin showed beneficial effects on CVD risk factors. Many dietary interventions were less conclusive because of the heterogeneity of study populations, small sample sizes, and short intervention windows or follow-up. Diet, lifestyle, probiotics, or drug interventions can modulate the gut microbiome and decrease risk markers or risk factors related to CVD. Yet, their effects on clinical endpoints remain to be determined.<\/jats:p>","DOI":"10.3390\/ijms252413529","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T03:40:56Z","timestamp":1734493256000},"page":"13529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Gut\u2013Heart Axis: Effects of Intestinal Microbiome Modulation on Cardiovascular Disease\u2014Ready for Therapeutic Interventions?"],"prefix":"10.3390","volume":"25","author":[{"given":"Alexandra","family":"Sagmeister","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-1767","authenticated-orcid":false,"given":"Christian M.","family":"Matter","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara E.","family":"St\u00e4hli","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scharl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, July 15). Cardiovascular Diseases (CVDs). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_2","first-page":"e563","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41467-017-00900-1","article-title":"The gut microbiome in atherosclerotic cardiovascular disease","volume":"8","author":"Jie","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/ncomms2266","article-title":"Symptomatic atherosclerosis is associated with an altered gut metagenome","volume":"3","author":"Karlsson","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yoshida, N., Yamashita, T., Kishino, S., Watanabe, H., Sasaki, K., Sasaki, D., Tabata, T., Sugiyama, Y., Kitamura, N., and Saito, Y. (2020). A possible beneficial effect of Bacteroides on faecal lipopolysaccharide activity and cardiovascular diseases. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69983-z"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Marchesi, J.R., and Ravel, J. (2015). The vocabulary of microbiome research: A proposal. Microbiome, 3.","DOI":"10.1186\/s40168-015-0094-5"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Berg, G., Rybakova, D., Fischer, D., Cernava, T., Verg\u00e8s, M.-C.C., Charles, T., Chen, X., Cocolin, L., Eversole, K., and Corral, G.H. (2020). Microbiome definition re-visited: Old concepts and new challenges. Microbiome, 8.","DOI":"10.1186\/s40168-020-00875-0"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dupr\u00e9, J., and O\u2019Malley, M.A. (2013). Varieties of Living Things: Life at the Intersection of Lineage and Metabolism. Vitalism and the Scientific Image in Post-Enlightenment Life Science, Springer.","DOI":"10.1007\/978-94-007-2445-7_13"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1002\/jnr.24476","article-title":"The role of inflammation and the gut microbiome in depression and anxiety","volume":"97","author":"Peirce","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbi.2015.03.016","article-title":"Altered fecal microbiota composition in patients with major depressive disorder","volume":"48","author":"Jiang","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hilty, M., Burke, C., Pedro, H., Cardenas, P., Bush, A., Bossley, C., Davies, J., Ervine, A., Poulter, L., and Pachter, L. (2010). Disordered microbial communities in asthmatic airways. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008578"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/eurheartj\/eht271","article-title":"The heart and the gut","volume":"35","author":"Rogler","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/MOG.0b013e328353e61e","article-title":"Inflammatory bowel disease pathogenesis","volume":"28","author":"Scharl","year":"2012","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaaw1815","DOI":"10.1126\/scitranslmed.aaw1815","article-title":"Transforming medicine with the microbiome","volume":"11","author":"Zmora","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.yjmcc.2020.12.001","article-title":"Gut microbiome\u2014A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review","volume":"152","author":"Mamic","year":"2021","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.cell.2020.02.016","article-title":"A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors","volume":"180","author":"Nemet","year":"2020","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/eurheartj\/ehab644","article-title":"Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism","volume":"43","author":"Haghikia","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1096\/fj.00-0359fje","article-title":"Anti-inflammatory effects of sodium butyrate on human monocytes: Potent inhibition of IL-12 and up-regulation of IL-10 production","volume":"14","author":"Saemann","year":"2000","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Janeiro, M.H., Ramirez, M.J., Milagro, F.I., Martinez, J.A., and Solas, M. (2018). Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients, 10.","DOI":"10.3390\/nu10101398"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1099\/jmm.0.053587-0","article-title":"Phospholipid catabolism by gut microbiota and the risk of cardiovascular disease","volume":"62","author":"Sitaraman","year":"2013","journal-title":"J. Med. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2016.02.011","article-title":"Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk","volume":"165","author":"Zhu","year":"2016","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1016\/j.jacc.2019.03.024","article-title":"Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review","volume":"73","author":"Tang","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","first-page":"1","article-title":"Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology","volume":"11","author":"Molinaro","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_25","first-page":"1","article-title":"Circulating bile acids concentration is predictive of coronary artery disease in human","volume":"11","author":"Duboc","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1073\/pnas.0400046101","article-title":"Expression and activation of the farnesoid X receptor in the vasculature","volume":"101","author":"Walsh","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9435","DOI":"10.1074\/jbc.M209706200","article-title":"A G protein-coupled receptor responsive to bile acids","volume":"278","author":"Kawamata","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1161\/ATVBAHA.107.152694","article-title":"Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration","volume":"27","author":"Li","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13098-017-0299-9","article-title":"Bile acids at the cross-roads of gut microbiome\u2013host cardiometabolic interactions","volume":"9","author":"Ryan","year":"2017","journal-title":"Diabetol. Amp; Metab. Syndr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.aav3487","article-title":"Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy","volume":"366","author":"Ronchi","year":"2019","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.vph.2018.01.005","article-title":"A positive feedback loop between IL-1beta, LPS and NEU1 may promote atherosclerosis by enhancing a pro-inflammatory state in monocytes and macrophages","volume":"103\u2013105","author":"Sieve","year":"2018","journal-title":"Vasc. Pharmacol."},{"key":"ref_32","first-page":"144","article-title":"Systematic Reviews: What Do You Need to Know to Get Started?","volume":"68","author":"Charrois","year":"2015","journal-title":"Can. J. Hosp. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.recesp.2021.06.016","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"74","author":"Page","year":"2021","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e012401","DOI":"10.1161\/JAHA.119.012401","article-title":"Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome","volume":"8","author":"Tovar","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e13935","DOI":"10.14814\/phy2.13935","article-title":"Effects of short-term endurance exercise on gut microbiota in elderly men","volume":"6","author":"Taniguchi","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000510646","article-title":"The Acute Effect of Meal Timing on the Gut Microbiome and the Cardiometabolic Health of the Host: A Crossover Randomized Control Trial","volume":"76","author":"Papadopoulou","year":"2020","journal-title":"Ann. Nutr. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1210\/clinem\/dgaa644","article-title":"Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients","volume":"106","author":"Guo","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Erickson, M.L., Malin, S.K., Wang, Z., Brown, J.M., Hazen, S.L., and Kirwan, J.P. (2019). Effects of Lifestyle Intervention on Plasma Trimethylamine N-Oxide in Obese Adults. Nutrients, 11.","DOI":"10.3390\/nu11010179"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/mi.2016.42","article-title":"Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice","volume":"10","author":"Yang","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_41","unstructured":"Das, B., and Singh, V. (2022). Human Microbiome in Health and Disease\u2014Part B, Academic Press."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/s41564-018-0272-x","article-title":"Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model","volume":"3","author":"Kasahara","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.cmet.2018.05.006","article-title":"Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota","volume":"27","author":"Cignarella","year":"2018","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.clnu.2020.05.025","article-title":"Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: Can SCFAs play a role?","volume":"40","author":"Vitale","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13073-022-01015-z","article-title":"The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: A randomized controlled trial","volume":"14","author":"Rinott","year":"2022","journal-title":"Genome Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1007\/s00394-021-02538-8","article-title":"Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: Possible links with gut microbiome, insulin resistance and inflammation","volume":"60","author":"Tagliamonte","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1007\/s00394-019-02050-0","article-title":"Influence of a 3-month low-calorie Mediterranean diet compared to the vegetarian diet on human gut microbiota and SCFA: The CARDIVEG Study","volume":"59","author":"Pagliai","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1039\/C9FO00333A","article-title":"A Mediterranean diet does not alter plasma trimethylamine N-oxide concentrations in healthy adults at risk for colon cancer","volume":"10","author":"Griffin","year":"2019","journal-title":"Food Funct."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22082","DOI":"10.1074\/jbc.M110.117713","article-title":"Dissecting the in vivo metabolic potential of two human gut acetogens","volume":"285","author":"Rey","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1984104","DOI":"10.1080\/19490976.2021.1984104","article-title":"Akkermansia muciniphila: Is it the Holy Grail for ameliorating metabolic diseases?","volume":"13","author":"Yan","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1161\/CIRCULATIONAHA.115.019645","article-title":"Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe-\/-Mice","volume":"133","author":"Li","year":"2016","journal-title":"Circulation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nm.4236","article-title":"A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice","volume":"23","author":"Plovier","year":"2017","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.pcad.2018.04.006","article-title":"Mediterranean Diet and Cardiovascular Disease Prevention: What Do We Know?","volume":"61","year":"2018","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_54","first-page":"788","article-title":"Resistant Starch Type-2 Supplementation Does Not Decrease Trimethylamine N-Oxide (TMAO) Plasma Level in Hemodialysis Patients","volume":"41","author":"Kemp","year":"2022","journal-title":"J. Am. Nutr. Assoc."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ranaivo, H., Zhang, Z., Alligier, M., Van Den Berghe, L., Sothier, M., Lambert-Porcheron, S., Feugier, N., Cuerq, C., Machon, C., and Neyrinck, A.M. (2022). Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-12920-z"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111701","DOI":"10.1016\/j.foodres.2022.111701","article-title":"Improvement in cardiometabolic risk markers following an oatmeal diet is associated with gut microbiota in mildly hypercholesterolemic individuals","volume":"160","author":"Xu","year":"2022","journal-title":"Food Res. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1007\/s00394-022-02836-9","article-title":"Impact of wheat aleurone on biomarkers of cardiovascular disease, gut microbiota and metabolites in adults with high body mass index: A double-blind, placebo-controlled, randomized clinical trial","volume":"61","author":"Fava","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2044722","DOI":"10.1080\/19490976.2022.2044722","article-title":"Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk","volume":"14","author":"Ranaivo","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"McCann, S.E., Hullar, M.A.J., Tritchler, D.L., Cortes-Gomez, E., Yao, S., Davis, W., O'Connor, T., Erwin, D., Thompson, L.U., and Yan, L. (2021). Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry. Nutrients, 13.","DOI":"10.3390\/nu13030919"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1093\/ajcn\/nqaa026","article-title":"Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: A randomized crossover trial","volume":"111","author":"Eriksen","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"de Mello, V.D., Paananen, J., Lindstr\u00f6m, J., Lankinen, M.A., Shi, L., Kuusisto, J., Pihlajam\u00e4ki, J., Auriola, S., Lehtonen, M., and Rolandsson, O. (2017). Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci. Rep., 7.","DOI":"10.1038\/srep46337"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.tjnut.2022.11.009","article-title":"A water-soluble tomato extract rich in secondary plant metabolites lowers trimethylamine-n-oxide and modulates gut microbiota: A randomized, double-blind, placebo-controlled cross-over study in overweight and obese adults","volume":"153","author":"Rehman","year":"2023","journal-title":"J. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1016\/j.clnu.2022.08.024","article-title":"The effects of Aronia berry (poly)phenol supplementation on arterial function and the gut microbiome in middle aged men and women: Results from a randomized controlled trial","volume":"41","author":"Xu","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1053\/j.jrn.2022.01.010","article-title":"Can Resveratrol Supplementation Reduce Uremic Toxin Plasma Levels From the Gut Microbiota in Nondialyzed Patients With Chronic Kidney Disease?","volume":"32","author":"Alvarenga","year":"2022","journal-title":"J. Ren. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1093\/jn\/nxac037","article-title":"Red Raspberry and Fructo-Oligosaccharide Supplementation, Metabolic Biomarkers, and the Gut Microbiota in Adults with Prediabetes: A Randomized Crossover Clinical Trial","volume":"152","author":"Zhang","year":"2022","journal-title":"J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1039\/D1FO03942C","article-title":"Hypertension- and glycaemia-lowering effects of a grape-pomace-derived seasoning in high-cardiovascular risk and healthy subjects. Interplay with the gut microbiome","volume":"13","author":"Taladrid","year":"2022","journal-title":"Food Funct."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1093\/ajcn\/nqac286","article-title":"A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition","volume":"116","author":"Haas","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1007\/s00394-021-02680-3","article-title":"Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects","volume":"61","author":"Gargari","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s00592-020-01494-9","article-title":"Diets naturally rich in polyphenols and\/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals","volume":"57","author":"Vetrani","year":"2020","journal-title":"Acta Diabetol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1093\/ajcn\/nqz075","article-title":"Effects of aronia berry (poly)phenols on vascular function and gut microbiota: A double-blind randomized controlled trial in adult men","volume":"110","author":"Istas","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1039\/C8FO00962G","article-title":"Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults","volume":"9","author":"Angiletta","year":"2018","journal-title":"Food Funct."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1039\/C5FO00669D","article-title":"Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers","volume":"6","author":"Li","year":"2015","journal-title":"Food Funct."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.clnu.2018.11.028","article-title":"Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study","volume":"38","author":"Costabile","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1016\/j.numecd.2022.04.007","article-title":"Effect of Atkins versus a low-fat diet on gut microbiota, and cardiometabolic markers in obese women following an energy-restricted diet: Randomized, crossover trial","volume":"32","author":"Mousavi","year":"2022","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1136\/gutjnl-2018-317609","article-title":"Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: A 6-month randomised controlled-feeding trial","volume":"68","author":"Wan","year":"2019","journal-title":"Gut"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2021.1875796","article-title":"Blautia-A New Funct. Genus Potential Probiotic Prop?","volume":"13","author":"Liu","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1136\/gutjnl-2014-307649","article-title":"Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn\u2019s disease","volume":"65","author":"Quevrain","year":"2016","journal-title":"Gut"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"G589","DOI":"10.1152\/ajpgi.00488.2011","article-title":"Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine","volume":"303","author":"Derrien","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"14691","DOI":"10.1073\/pnas.1005963107","article-title":"Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa","volume":"107","author":"Cavalieri","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/eurheartj\/ehy799","article-title":"Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women","volume":"40","author":"Wang","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e1700976","DOI":"10.1002\/mnfr.201700976","article-title":"The Effect of Lean-Seafood and Non-Seafood Diets on Fecal Metabolites and Gut Microbiome: Results from a Randomized Crossover Intervention Study","volume":"63","author":"Schmedes","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12944-022-01702-1","article-title":"Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels-a randomized controlled trial in healthy individuals","volume":"21","author":"Gaundal","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/00365513.2022.2102540","article-title":"Reduced gut microbial diversity in familial hypercholesterolemia with no effect of omega-3 polyunsaturated fatty acids intervention\u2014A pilot trial","volume":"82","author":"Hande","year":"2022","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1093\/jn\/nxz289","article-title":"Walnuts and Vegetable Oils Containing Oleic Acid Differentially Affect the Gut Microbiota and Associations with Cardiovascular Risk Factors: Follow-up of a Randomized, Controlled, Feeding Trial in Adults at Risk for Cardiovascular Disease","volume":"150","author":"Tindall","year":"2020","journal-title":"J. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3089303","DOI":"10.1155\/2016\/3089303","article-title":"Understanding the Impact of Omega-3 Rich Diet on the Gut Microbiota","volume":"2016","author":"Noriega","year":"2016","journal-title":"Case Rep. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Costantini, L., Molinari, R., Farinon, B., and Merendino, N. (2017). Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122645"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1017\/S0007114520003402","article-title":"Beneficial effect on serum cholesterol levels, but not glycaemic regulation, after replacing SFA with PUFA for 3 d: A randomised crossover trial","volume":"125","author":"Gaundal","year":"2021","journal-title":"Br. J. Nutr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"25145","DOI":"10.3402\/fnr.v58.25145","article-title":"Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: A systematic review","volume":"58","author":"Schwab","year":"2014","journal-title":"Food Nutr. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/joim.12543","article-title":"Potential health hazards of eating red meat","volume":"281","author":"Wolk","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1136\/gutjnl-2022-329201","article-title":"Gut microbiome modulates the effects of a personalised postprandial-targeting (PPT) diet on cardiometabolic markers: A diet intervention in pre-diabetes","volume":"72","author":"Godneva","year":"2023","journal-title":"Gut"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.tjnut.2023.03.013","article-title":"Effects of Adding Lean Red Meat to a U.S.-Style Healthy Vegetarian Dietary Pattern on Gut Microbiota and Cardiovascular Risk Factors in Young Adults: A Crossover Randomized Controlled Trial","volume":"153","author":"Wang","year":"2023","journal-title":"J. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.nutres.2020.04.002","article-title":"Whole egg consumption increases plasma choline and betaine without affecting TMAO levels or gut microbiome in overweight postmenopausal women","volume":"78","author":"Zhu","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1007\/s00394-017-1563-3","article-title":"Improvement in cardiometabolic risk markers following a multifunctional diet is associated with gut microbial taxa in healthy overweight and obese subjects","volume":"57","author":"Marungruang","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Burton, K.J., Kruger, R., Scherz, V., Munger, L.H., Picone, G., Vionnet, N., Bertelli, C., Greub, G., Capozzi, F., and Vergeres, G. (2020). Trimethylamine-N-Oxide Postprandial Response in Plasma and Urine Is Lower After Fermented Compared to Non-Fermented Dairy Consumption in Healthy Adults. Nutrients, 12.","DOI":"10.3390\/nu12010234"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gutjnl-2018-318155","article-title":"Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: Towards a gut sphingomyelin-cholesterol interplay","volume":"69","author":"Vors","year":"2020","journal-title":"Gut"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ayyash, M., and Liu, S.Q. (2023). Special Issue Probiotics, Prebiotics and Functional Foods: Health Benefits and Biosafety. Microorganisms, 11.","DOI":"10.3390\/microorganisms11051218"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ajcnut.2022.10.013","article-title":"Chronic consumption of probiotics, oats, and apples has differential effects on postprandial bile acid profile and cardiometabolic disease risk markers compared with an isocaloric control (cornflakes): A randomized trial","volume":"117","author":"Pushpass","year":"2023","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2003176","DOI":"10.1080\/19490976.2021.2003176","article-title":"Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: A double blinded placebo controlled randomized study","volume":"14","author":"Wang","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1007\/s00394-022-02904-0","article-title":"Effects of enriched seafood sticks (heat-inactivated B. animalis subsp. lactis CECT 8145, inulin, omega-3) on cardiometabolic risk factors and gut microbiota in abdominally obese subjects: Randomized controlled trial","volume":"61","author":"Companys","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3920\/BM2020.0039","article-title":"Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults","volume":"11","author":"Trotter","year":"2020","journal-title":"Benef. Microbes"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1007\/s00394-020-02207-2","article-title":"Effect of probiotics on the intestinal microbiota of hemodialysis patients: A randomized trial","volume":"59","author":"Liu","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_102","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_103","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/s12602-018-9411-1","article-title":"Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: A Pilot Study","volume":"11","author":"Borges","year":"2019","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1038\/s41366-018-0220-0","article-title":"Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: A randomized controlled trial","volume":"43","author":"Pedret","year":"2019","journal-title":"Int. J. Obes."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12934-017-0691-z","article-title":"Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria","volume":"16","author":"LeBlanc","year":"2017","journal-title":"Microb. Cell Fact."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/obr.12626","article-title":"Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: A systematic review and meta-analysis of randomized controlled trials","volume":"19","author":"Borgeraas","year":"2018","journal-title":"Obes. Rev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12882-020-02177-x","article-title":"The effects of 16-weeks of prebiotic supplementation and aerobic exercise training on inflammatory markers, oxidative stress, uremic toxins, and the microbiota in pre-dialysis kidney patients: A randomized controlled trial-protocol paper","volume":"21","author":"Headley","year":"2020","journal-title":"BMC Nephrol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1210\/clinem\/dgac210","article-title":"Cardiovascular Benefits of Empagliflozin Are Associated With Gut Microbiota and Plasma Metabolites in Type 2 Diabetes","volume":"107","author":"Deng","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_110","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_111","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.34067\/KID.0003942020","article-title":"Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins and Inflammation in CKD","volume":"1","author":"Kimber","year":"2020","journal-title":"Kidney360"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Kummen, M., Solberg, O.G., Storm-Larsen, C., Holm, K., Ragnarsson, A., Troseid, M., Vestad, B., Skardal, R., Yndestad, A., and Ueland, T. (2020). Rosuvastatin alters the genetic composition of the human gut microbiome. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-62261-y"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Cho, C.E., Aardema, N.D.J., Bunnell, M.L., Larson, D.P., Aguilar, S.S., Bergeson, J.R., Malysheva, O.V., Caudill, M.A., and Lefevre, M. (2020). Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men. Nutrients, 12.","DOI":"10.3390\/nu12082220"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:54:11Z","timestamp":1760115251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,17]]},"references-count":113,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413529"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413529","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,17]]}}}