{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:21:10Z","timestamp":1787253670844,"version":"build-2736575974"},"reference-count":206,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands Heart Foundation","award":["2018-27"],"award-info":[{"award-number":["2018-27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Despite advances in preventive measures and treatment options, cardiovascular disease (CVD) remains the number one cause of death globally. Recent research has challenged the traditional risk factor profile and highlights the potential contribution of non-traditional factors in CVD, such as the gut microbiota and its metabolites. Disturbances in the gut microbiota have been repeatedly associated with CVD, including atherosclerosis and hypertension. Mechanistic studies support a causal role of microbiota-derived metabolites in disease development, such as short-chain fatty acids, trimethylamine-N-oxide, and bile acids, with the latter being elaborately discussed in this review. Bile acids represent a class of cholesterol derivatives that is essential for intestinal absorption of lipids and fat-soluble vitamins, plays an important role in cholesterol turnover and, as more recently discovered, acts as a group of signaling molecules that exerts hormonal functions throughout the body. Studies have shown mediating roles of bile acids in the control of lipid metabolism, immunity, and heart function. Consequently, a picture has emerged of bile acids acting as integrators and modulators of cardiometabolic pathways, highlighting their potential as therapeutic targets in CVD. In this review, we provide an overview of alterations in the gut microbiota and bile acid metabolism found in CVD patients, describe the molecular mechanisms through which bile acids may modulate CVD risk, and discuss potential bile-acid-based treatment strategies in relation to CVD.<\/jats:p>","DOI":"10.3390\/nu15081850","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:57:08Z","timestamp":1681268228000},"page":"1850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Emerging Roles of Gut Microbial Modulation of Bile Acid Composition in the Etiology of Cardiovascular Diseases"],"prefix":"10.3390","volume":"15","author":[{"given":"Tess","family":"Yntema","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debby P. Y.","family":"Koonen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2518-737X","authenticated-orcid":false,"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"},{"name":"European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","unstructured":"(2022, November 09). Cardiovascular Diseases (CVDs). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics\u20142021 Update: A Report From the American Heart Association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1161\/CIRCULATIONAHA.118.037137","article-title":"Twenty Year Trends and Sex Differences in Young Adults Hospitalized with Acute Myocardial Infarction: The ARIC Community Surveillance Study","volume":"139","author":"Arora","year":"2019","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1161\/CIRCRESAHA.115.307611","article-title":"Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease","volume":"118","author":"Herrington","year":"2016","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","article-title":"Mechanisms of plaque formation and rupture","volume":"114","author":"Bentzon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/S0735-1097(98)00093-X","article-title":"Interactive Role of Infection, Inflammation and Traditional Risk Factors in Atherosclerosis and Coronary Artery Disease","volume":"31","author":"Mehta","year":"1998","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fcvm.2020.00088","article-title":"The Evolving Understanding and Approach to Residual Cardiovascular Risk Management","volume":"7","author":"Dhindsa","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrcardio.2016.183","article-title":"Role of gut microbiota in atherosclerosis","volume":"14","author":"Jonsson","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1161\/CIRCRESAHA.120.316242","article-title":"Gut Microbiota and Cardiovascular Disease","volume":"127","author":"Witkowski","year":"2020","journal-title":"Circ. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut microbial metabolites in obesity, NAFLD and T2DM","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The intestinal microbiota fuelling metabolic inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s13668-018-0248-8","article-title":"Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health","volume":"7","author":"Chambers","year":"2018","journal-title":"Curr. Nutr. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1093\/eurheartj\/ehx342","article-title":"Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: A systematic review and dose-response meta-analysis","volume":"38","author":"Schiattarella","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11883-020-00863-7","article-title":"Nutrition and Gastrointestinal Microbiota, Microbial-Derived Secondary Bile Acids, and Cardiovascular Disease","volume":"22","author":"Matthan","year":"2020","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1097\/MJT.0b013e31815a69fc","article-title":"The Forgotten Bile Acid Sequestrants: Is Now a Good Time to Remember?","volume":"14","author":"Bays","year":"2007","journal-title":"Am. J. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/0002-9149(84)90854-3","article-title":"Lipid research clinics coronary primary prevention trial: Results and implications","volume":"54","author":"Rifkind","year":"1984","journal-title":"Am. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0140-6736(92)90863-X","article-title":"Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas Atherosclerosis regression study","volume":"339","author":"Watts","year":"1992","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.atherosclerosis.2016.07.923","article-title":"Angiographic progression of coronary atherosclerosis in patients with familial hypercholesterolaemia treated with non-statin therapy: Impact of a fat-modified diet and a resin","volume":"252","author":"Watts","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nrendo.2014.60","article-title":"Beyond intestinal soap\u2014Bile acids in metabolic control","volume":"10","author":"Kuipers","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1194\/jlr.R024794","article-title":"Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease","volume":"53","author":"Porez","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3748\/wjg.15.804","article-title":"Bile acids: Chemistry, physiology, and pathophysiology","volume":"15","author":"Monte","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.biochem.72.121801.161712","article-title":"The enzymes, regulation, and genetics of bile acid synthesis","volume":"72","author":"Russell","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1194\/jlr.R500013-JLR200","article-title":"Bile salt biotransformations by human intestinal bacteria","volume":"47","author":"Ridlon","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/physrev.00010.2008","article-title":"Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation","volume":"89","author":"Lefebvre","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism","volume":"24","author":"Sayin","year":"2016","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrd2619","article-title":"Targeting bile-acid signalling for metabolic diseases","volume":"24","author":"Thomas","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1172\/JCI0216309","article-title":"Cholic acid mediates negative feedback regulation of bile acid synthesis in mice","volume":"110","author":"Olin","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","article-title":"Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist","volume":"17","author":"Sayin","year":"2013","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101493","DOI":"10.1016\/j.beem.2021.101493","article-title":"Gut microbiome and bile acids in obesity-related diseases","volume":"35","author":"Li","year":"2021","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1752-8062.2011.00272.x","article-title":"Bile acids regulate cardiovascular function","volume":"4","author":"Khurana","year":"2011","journal-title":"Clin. Transl. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/cphy.c120023","article-title":"Bile acid metabolism and signaling","volume":"3","author":"Chiang","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41574-019-0266-7","article-title":"Bile acids in glucose metabolism and insulin signalling\u2014Mechanisms and research needs","volume":"15","author":"Ahmad","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17562848211018098","DOI":"10.1177\/17562848211018098","article-title":"Critical roles of bile acids in regulating intestinal mucosal immune responses","volume":"14","author":"Sun","year":"2021","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108212","DOI":"10.1016\/j.celrep.2020.108212","article-title":"Genetic and Microbial Associations to Plasma and Fecal Bile Acids in Obesity Relate to Plasma Lipids and Liver Fat Content","volume":"33","author":"Chen","year":"2020","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5603","DOI":"10.1128\/AEM.70.9.5603-5612.2004","article-title":"Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidum strains","volume":"70","author":"Kim","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1128\/aem.61.7.2514-2520.1995","article-title":"Cloning and Characterization of a Conjugated Bile Acid Hydrolase Gene from Clostridium perfringens","volume":"61","author":"Coleman","year":"1995","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1046\/j.1365-2958.2002.03080.x","article-title":"Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis","volume":"45","author":"Dussurget","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1128\/IAI.73.2.894-904.2005","article-title":"Contribution of three bile-associated loci, bsh, pva, and btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes","volume":"73","author":"Begley","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8795","DOI":"10.1128\/AEM.02519-12","article-title":"Identification and characterization of a bile salt hydrolase from Lactobacillus salivarius for development of novel alternatives to antibiotic growth promoters","volume":"78","author":"Wang","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3168\/jds.S0022-0302(99)75256-2","article-title":"Bile salt hydrolase activity of three strains of Lactobacillus acidophilus","volume":"82","author":"Corzo","year":"1999","journal-title":"J. Dairy Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0005-2744(76)90068-1","article-title":"Purification and characterization of bile salt hydrolase from Bacteroides fragilis subsp. fragilis","volume":"452","author":"Stellwag","year":"1976","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40168-019-0628-3","article-title":"Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome","volume":"7","author":"Song","year":"2019","journal-title":"Microbiome"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/19490976.2020.1748261","article-title":"Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health","volume":"11","author":"Jia","year":"2020","journal-title":"Gut Microbes."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41586-020-2047-9","article-title":"Global chemical effects of the microbiome include new bile-acid conjugations","volume":"579","author":"Quinn","year":"2020","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e00235-18","DOI":"10.1128\/AEM.00235-18","article-title":"Metabolism of oxo-bile acids and characterization of recombinant 12\u03b1- hydroxysteroid dehydrogenases from bile acid 7\u03b1-dehydroxylating human gut bacteria","volume":"84","author":"Doden","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature12347","article-title":"Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome","volume":"499","author":"Yoshimoto","year":"2013","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00204-011-0648-7","article-title":"Carcinogenicity of deoxycholate, a secondary bile acid","volume":"85","author":"Bernstein","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/S0016-5085(96)70024-0","article-title":"7a-Dehydroxylating Bacteria Enhance Deoxycholic Acid Input and Cholesterol Saturation of Bile in Patients With Gallstones","volume":"111","author":"Berr","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrmicro.2017.149","article-title":"Microbial modulation of cardiovascular disease","volume":"16","author":"Brown","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.bbalip.2007.10.008","article-title":"Clostridium scindens baiCD and baiH genes encode stereo-specific 7\u03b1\/7\u03b2-hydroxy-3-oxo-\u03944-cholenoic acid oxidoreductases","volume":"1781","author":"Kang","year":"2008","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fmed.2017.00163","article-title":"Interactions between bacteria and bile salts in the gastrointestinal and hepatobiliary tracts","volume":"4","author":"Urdaneta","year":"2017","journal-title":"Front. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1073\/pnas.0600780103","article-title":"How bile acids confer gut mucosal protection against bacteria","volume":"103","author":"Hofmann","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"396","DOI":"10.3389\/fmicb.2013.00396","article-title":"Bile resistance mechanisms in Lactobacillus and Bifidobacterium","volume":"4","author":"Ruiz","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"245\u2013257.e6","DOI":"10.1016\/j.chom.2020.05.013","article-title":"Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level","volume":"28","author":"Kenny","year":"2020","journal-title":"Cell. Host Microbe."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/s41564-022-01195-9","article-title":"Characterization of interactions of dietary cholesterol with the murine and human gut microbiome","volume":"7","author":"Le","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1038\/s41564-022-01176-y","article-title":"A biosynthetic pathway for the selective sulfonation of steroidal metabolites by human gut bacteria","volume":"7","author":"Yao","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1161\/01.CIR.98.7.628","article-title":"Confirmed Previous Infection With Chlamydia pneumoniae (TWAR) and Its Presence in Early Coronary Atherosclerosis","volume":"98","author":"Davidson","year":"1998","journal-title":"Circulation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1073\/pnas.1011383107","article-title":"Human oral, gut, and plaque microbiota in patients with atherosclerosis","volume":"108","author":"Koren","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41569-022-00771-0","article-title":"The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease","volume":"20","author":"Chakaroun","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e01206-14","DOI":"10.1128\/mBio.01206-14","article-title":"Bacteria present in carotid arterial plaques are found as biofilm deposits which may contribute to enhanced risk of plaque rupture","volume":"5","author":"Lanter","year":"2014","journal-title":"MBio"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1161\/CIRCULATIONAHA.105.579979","article-title":"Detection of diverse bacterial signatures in atherosclerotic lesions of patients with coronary heart disease","volume":"113","author":"Ott","year":"2006","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.1021\/acs.jafc.0c00225","article-title":"Gut Microbiome-Based Diagnostic Model to Predict Coronary Artery Disease","volume":"68","author":"Zheng","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_64","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_65","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1152\/physiolgenomics.00070.2018","article-title":"Dysbiosis signatures of gut microbiota in coronary artery disease","volume":"50","author":"Zhu","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e002699","DOI":"10.1161\/JAHA.115.002699","article-title":"Dysbiosis of gut microbiota with reduced trimethylamine-n-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack","volume":"4","author":"Yin","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","unstructured":"Toya, T., Corban, M.T., Marrietta, E., Horwath, I.E., Lerman, L.O., Murray, J.A., and Lerman, A. (2020). Coronary artery disease is associated with an altered gut microbiome composition. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227147"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40168-019-0683-9","article-title":"Alterations in the gut microbiome and metabolism with coronary artery disease severity","volume":"7","author":"Liu","year":"2019","journal-title":"Microbiome"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"22525","DOI":"10.1038\/srep22525","article-title":"Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease","volume":"6","author":"Feng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1161\/CIRCULATIONAHA.118.033714","article-title":"Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis","volume":"138","author":"Yoshida","year":"2018","journal-title":"Circulation"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Verhaar, B.J.H., Prodan, A., Nieuwdorp, M., and Muller, M. (2020). Gut microbiota in hypertension and atherosclerosis: A review. Nutrients, 12.","DOI":"10.3390\/nu12102982"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2217\/fmb-2016-0130","article-title":"Roseburia spp.: A marker of health?","volume":"12","author":"Smida","year":"2017","journal-title":"Future Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.bpg.2017.09.011","article-title":"Action and function of Faecalibacterium prausnitzii in health and disease","volume":"31","author":"Andrade","year":"2017","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1086\/314046","article-title":"Veillonella parvula Meningitis: Case Report and Review of Veillonella Infections","volume":"31","author":"Bhatti","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/0022034511435101","article-title":"Increased atherogenesis during Streptococcus mutans infection in ApoE-null mice","volume":"91","author":"Kesavalu","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8145","DOI":"10.1128\/JB.00983-08","article-title":"Characterization of a Streptococcus sp.-Veillonella sp. community micromanipulated from dental plaque","volume":"190","author":"Chalmers","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nm876","article-title":"Pneumococcal vaccination decreases atherosclerotic lesion formation molecular mimicry between Streptococcus pneumoniae and oxidized LDL","volume":"9","author":"Binder","year":"2003","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nchembio.1864","article-title":"A biosynthetic pathway for a prominent class of microbiota-derived bile acids","volume":"11","author":"Devlin","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1177\/0884533615609896","article-title":"Role of the gut microbiome in obesity and diabetes mellitus","volume":"30","author":"Barlow","year":"2015","journal-title":"Nutr. Clin. Pract."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1053\/j.gastro.2009.03.030","article-title":"Obesity and the Microbiota","volume":"136","author":"Tilg","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e019820","DOI":"10.1161\/JAHA.120.019820","article-title":"Glycoursodeoxycholic acid ameliorates atherosclerosis and alters gut microbiota in apolipoprotein e\u2013deficient mice","volume":"10","author":"Huang","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/s41587-020-0549-5","article-title":"Directed remodeling of the mouse gut microbiome inhibits the development of atherosclerosis","volume":"38","author":"Chen","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1186\/s12967-020-02539-x","article-title":"Gut microbiota from coronary artery disease patients contributes to vascular dysfunction in mice by regulating bile acid metabolism and immune activation","volume":"18","author":"Liu","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1161\/CIRCRESAHA.118.313234","article-title":"A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis","volume":"124","author":"Brandsma","year":"2019","journal-title":"Circ. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"22661","DOI":"10.1038\/s41598-021-02144-y","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_87","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.atherosclerosis.2019.11.026","article-title":"Fasting serum total bile acid level is associated with coronary artery disease, myocardial infarction and severity of coronary lesions","volume":"292","author":"Li","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Steiner, C., Othman, A., Saely, C.H., Rein, P., Drexel, H., von Eckardstein, A., and Rentsch, K.M. (2011). Bile acid metabolites in serum: Intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025006"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/gut.12.2.145","article-title":"Serum bile acids in liver disease","volume":"12","author":"Neale","year":"1971","journal-title":"Gut"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.phrs.2014.03.002","article-title":"The pharmacology of statins","volume":"88","author":"Sirtori","year":"2014","journal-title":"Pharmacol. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"15357","DOI":"10.1038\/s41598-017-15737-3","article-title":"Investigation of novel metabolites potentially involved in the pathogenesis of coronary heart disease using a UHPLC-QTOF\/MS-based metabolomics approach","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/1756283X10388682","article-title":"The association of bile acid excretion and atherosclerotic coronary artery disease","volume":"4","author":"Charach","year":"2011","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.atherosclerosis.2019.12.010","article-title":"Reduced bile acid excretion is an independent risk factor for stroke and mortality: A prospective follow-up study","volume":"293","author":"Charach","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1756283X17743420","DOI":"10.1177\/1756283X17743420","article-title":"Diminished bile acids excretion is a risk factor for coronary artery disease: 20-year follow up and long-term outcome","volume":"11","author":"Charach","year":"2018","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1172\/JCI21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"Watanabe","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.2337\/diabetes.52.5.1081","article-title":"Hepatic VLDL Production in ob\/ob Mice is Not Stimulated by Massive De Novo Lipogenesis but is Less Sensitive to the Suppressive Effects of Insulin","volume":"52","author":"Wiegman","year":"2003","journal-title":"Diabetes"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0022-2275(20)42003-6","article-title":"I review Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression","volume":"37","author":"Schoonjans","year":"1996","journal-title":"J. Lipid Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1172\/JCI88893","article-title":"Nutrient-sensing nuclear receptors PPAR and FXR control liver energy balance","volume":"127","author":"Preidis","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11010-005-9053-y","article-title":"Peroxisome proliferator-activated receptor-\u03b1 selective ligand reduces adiposity, improves insulin sensitivity and inhibits atherosclerosis in LDL receptor-deficient mice","volume":"285","author":"Srivastava","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3803\/EnM.2021.1100","article-title":"The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE\u2212\/\u2212FXR\u2212\/\u2212 Mice","volume":"36","author":"Lee","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1210\/me.2002-0120","article-title":"Bile acids induce the expression of the human peroxisome proliferator-activated receptor \u03b1 gene via activation of the farnesoid X receptor","volume":"17","author":"Torra","year":"2003","journal-title":"Mol. Endocrinol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1073\/pnas.051551698","article-title":"The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity","volume":"98","author":"Staudinger","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1194\/jlr.M800608-JLR200","article-title":"Activation of PXR induces hypercholesterolemia in wild-type and accelerates atherosclerosis in apoE deficient mice","volume":"50","author":"Zhou","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1194\/jlr.M017376","article-title":"Deficiency of PXR decreases atherosclerosis in apoE-deficient mice","volume":"52","author":"Sui","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1038\/emm.2014.38","article-title":"CD36, a scavenger receptor implicated in atherosclerosis","volume":"46","author":"Park","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"586980","DOI":"10.3389\/fendo.2020.586980","article-title":"Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1\/ApoE Double Knockout Mice: Differential Cardiovascular Outcome","volume":"11","author":"Zurkinden","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.taap.2014.12.005","article-title":"Individual bile acids have differential effects on bile acid signaling in mice","volume":"283","author":"Song","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"100134","DOI":"10.1016\/j.jlr.2021.100134","article-title":"Low production of 12\u03b1-hydroxylated bile acids prevents hepatic steatosis in Cyp2c70-\/- mice by reducing fat absorption","volume":"62","author":"Li","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1194\/jlr.M200469-JLR200","article-title":"Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-\/- mice by SC-435","volume":"44","author":"Bhat","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_111","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_112","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1152\/ajpheart.01075.2008","article-title":"Antiatherosclerotic effect of farnesoid X receptor","volume":"296","author":"Mencarelli","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_113","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_114","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_115","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1161\/01.RES.0000200400.55539.85","article-title":"Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells","volume":"98","author":"He","year":"2006","journal-title":"Circ. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cmet.2011.11.006","article-title":"TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading","volume":"14","author":"Pols","year":"2011","journal-title":"Cell. Metab."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1194\/jlr.M087239","article-title":"Simultaneous inhibition of FXR and TGR5 exacerbates atherosclerotic formation","volume":"59","author":"Masuda","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.molmet.2018.01.005","article-title":"Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR","volume":"9","author":"Jadhav","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.bbalip.2006.09.018","article-title":"Effects of FXR in foam-cell formation and atherosclerosis development","volume":"1761","author":"Guo","year":"2006","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1161\/01.ATV.0000235697.35431.05","article-title":"FXR deficiency causes reduced atherosclerosis in Ldlr-\/- mice","volume":"26","author":"Zhang","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1194\/jlr.M800619-JLR200","article-title":"Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR\u2212\/\u2212 and apoE\u2212\/\u2212 mice","volume":"50","author":"Hartman","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/hep.28712","article-title":"Farnesoid X Receptor Activation Increases Reverse Cholesterol Transport by Modulating Bile Acid Composition and Cholesterol Absorption in Mice","volume":"64","author":"Xu","year":"2016","journal-title":"Hepatology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e143865","DOI":"10.1172\/JCI142865","article-title":"Suppressing the intestinal farnesoid X receptor\/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis","volume":"131","author":"Wu","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Frosteg\u00e5rd, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-117"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"931066","DOI":"10.3389\/fcvm.2022.931066","article-title":"Identification and verification of immune-related biomarkers and immune infiltration in diabetic heart failure","volume":"9","author":"Zhong","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"7715","DOI":"10.4049\/jimmunol.176.12.7715","article-title":"CD4 T Cells Play Major Effector Role and CD8 T Cells Initiating Role in Spontaneous Autoimmune Myocarditis of HLA-DQ8 Transgenic IAb Knockout Nonobese Diabetic Mice 1","volume":"176","author":"Hayward","year":"2006","journal-title":"J. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"992653","DOI":"10.3389\/fcvm.2022.992653","article-title":"CD4+ T-lymphocytes exhibit biphasic kinetics post-myocardial infarction","volume":"9","author":"Kumar","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"732794","DOI":"10.3389\/fimmu.2021.732794","article-title":"Regulatory T Cells in Chronic Heart Failure","volume":"12","author":"Lu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1161\/CIRCRESAHA.121.318005","article-title":"Immune Cells and Immunotherapy for Cardiac Injury and Repair","volume":"128","author":"Rurik","year":"2021","journal-title":"Circ. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"E008997","DOI":"10.1161\/CIRCHEARTFAILURE.121.008997","article-title":"Estrogen Receptor-\u03b2 Agonists Modulate T-Lymphocyte Activation and Ameliorate Left Ventricular Remodeling during Chronic Heart Failure","volume":"15","author":"Rosenzweig","year":"2022","journal-title":"Circ. Heart Fail."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.apsb.2021.12.011","article-title":"Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases","volume":"12","author":"Guan","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1136\/gut.2010.212159","article-title":"Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease","volume":"60","author":"Gadaleta","year":"2011","journal-title":"Gut"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.jhep.2019.06.017","article-title":"FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis","volume":"71","author":"Sorribas","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.jhep.2015.12.010","article-title":"Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats","volume":"64","author":"Lario","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1073\/pnas.0509592103","article-title":"Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor","volume":"103","author":"Inagaki","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.toxlet.2019.08.024","article-title":"The protective effect of lithocholic acid on the intestinal epithelial barrier is mediated by the vitamin D receptor via a SIRT1\/Nrf2 and NF-\u03baB dependent mechanism in Caco-2 cells","volume":"316","author":"Yao","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-019-1785-z","article-title":"Bile acid metabolites control TH17 and Treg cell differentiation","volume":"576","author":"Hang","year":"2019","journal-title":"Nature"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1152\/ajpheart.01182.2005","article-title":"Bile acids induce adhesion molecule expression in endothelial cells through activation of reactive oxygen species, NF-B, and p38","volume":"291","author":"Qin","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e3467","DOI":"10.1097\/MD.0000000000003467","article-title":"The associations between the polymorphisms of Vitamin D receptor and coronary artery disease","volume":"95","author":"Lu","year":"2016","journal-title":"Medicine"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1210\/me.2011-1329","article-title":"Vitamin D receptor signaling inhibits atherosclerosis in Mice","volume":"26","author":"Szeto","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Latic, N., and Erben, R.G. (2020). Vitamin D and cardiovascular disease, with emphasis on hypertension, atherosclerosis, and heart failure. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186483"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1152\/ajpgi.00267.2012","article-title":"A novel mechanism for gut barrier dysfunction by dietary fat: Epithelial disruption by hydrophobic bile acids","volume":"304","author":"Stenman","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2481418","DOI":"10.1155\/2018\/2481418","article-title":"Deoxycholic acid-mediated sphingosine-1-phosphate receptor 2 signaling exacerbates DSS-induced colitis through promoting cathepsin b release","volume":"2018","author":"Zhao","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1819155","DOI":"10.1080\/19490976.2020.1819155","article-title":"Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation","volume":"12","author":"Wang","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s12265-021-10164-2","article-title":"Roles and Mechanisms of TGR5 in the Modulation of CD4+ T Cell Functions in Myocardial Infarction","volume":"15","author":"Wang","year":"2022","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.immuni.2016.09.008","article-title":"Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome","volume":"45","author":"Guo","year":"2016","journal-title":"Immunity"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"6115","DOI":"10.1038\/ncomms7115","article-title":"Small heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome","volume":"6","author":"Yang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1016\/j.celrep.2015.02.043","article-title":"Deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice","volume":"10","author":"Oh","year":"2015","journal-title":"Cell. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Weng, S., Sprague, J.E., Oh, J., Riek, A.E., Chin, K., Garcia, M., and Bernal-Mizrachi, C. (2013). Vitamin D Deficiency Induces High Blood Pressure and Accelerates Atherosclerosis in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054625"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/hep.30937","article-title":"Vitamin D Receptor Activation in Liver Macrophages Ameliorates Hepatic Inflammation, Steatosis, and Insulin Resistance in Mice","volume":"71","author":"Dong","year":"2020","journal-title":"Hepatology"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature13577","article-title":"The alarmin IL-33 promotes regulatory T-cell function in the intestine","volume":"513","author":"Schiering","year":"2014","journal-title":"Nature"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41586-022-04480-z","article-title":"Human gut bacteria produce \u03a4H17-modulating bile acid metabolites","volume":"603","author":"Paik","year":"2022","journal-title":"Nature"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.chom.2021.07.013","article-title":"A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1","volume":"29","author":"Li","year":"2021","journal-title":"Cell. Host Microbe."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","article-title":"Microbial bile acid metabolites modulate gut ROR\u03b3+ regulatory T cell homeostasis","volume":"577","author":"Song","year":"2020","journal-title":"Nature"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41586-020-2193-0","article-title":"Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells","volume":"581","author":"Campbell","year":"2020","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"24986","DOI":"10.1073\/pnas.2001966117","article-title":"VDR polymorphisms regulated t cells and t cell dependent inflammatory disease","volume":"117","author":"Lahore","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1093\/eurheartj\/ehs011","article-title":"Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia\/reperfusion injury","volume":"34","author":"Pu","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"H195","DOI":"10.1152\/ajpheart.00679.2008","article-title":"Chronic stimulation of farnesoid X receptor impairs nitric oxide sensitivity of vascular smooth muscle","volume":"296","author":"Kida","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/cvr\/cvm068","article-title":"FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells","volume":"77","author":"Zhang","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/cvr\/cvm016","article-title":"FXR-mediated regulation of eNOS expression in vascular endothelial cells","volume":"77","author":"Li","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.yjmcc.2005.07.014","article-title":"Hydrophilic bile salt ursodeoxycholic acid protects myocardium against reperfusion injury in a PI3K\/Akt dependent pathway","volume":"39","author":"Rajesh","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1161\/ATVBAHA.113.301565","article-title":"Bile Acid Receptor TGR5 Agonism Induces NO Production and Reduces Monocyte Adhesion in Vascular Endothelial Cells","volume":"33","author":"Thromb","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"302","DOI":"10.2174\/1874192401004010302","article-title":"The Endothelium and Its Role in Regulating Vascular Tone","volume":"4","author":"Sandoo","year":"2010","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.yjmcc.2020.10.014","article-title":"DCA-TGR5 signaling activation alleviates inflammatory response and improves cardiac function in myocardial infarction","volume":"151","author":"Wang","year":"2021","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1152\/ajpcell.00287.2006","article-title":"Angiotensin II cell signaling: Physiological and pathological effects in the cardiovascular system","volume":"292","author":"Mehta","year":"2007","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/hep.28890","article-title":"Bile Acid Excess Induces Cardiomyopathy and Metabolic Dysfunctions in the Heart","volume":"65","author":"Desai","year":"2017","journal-title":"Hepatology"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1002\/hep.23585","article-title":"Hypertrophic cardiomyopathy and dysregulation of cardiac energetics in a mouse model of biliary fibrosis","volume":"51","author":"Desai","year":"2010","journal-title":"Hepatology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1210\/en.2007-0805","article-title":"Functional vitamin D receptor (VDR) in the T-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility","volume":"149","author":"Tishkoff","year":"2008","journal-title":"Endocrinology"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41598-018-19708-0","article-title":"Effects of Vitamin D supplementation on inflammatory markers in heart failure: A systematic review and meta-analysis of randomized controlled trials","volume":"8","author":"Rodriguez","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1098\/rspb.2011.0624","article-title":"The structure and function of cardiac t-tubules in health and disease","volume":"278","author":"Ibrahim","year":"2011","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1001\/archinte.168.11.1174","article-title":"25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men a Prospective Study","volume":"168","author":"Giovannucci","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1001\/archinte.168.12.1340","article-title":"Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality","volume":"168","author":"Dobnig","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/CIRCULATIONAHA.107.706127","article-title":"Vitamin D deficiency and risk of cardiovascular disease","volume":"117","author":"Wang","year":"2008","journal-title":"Circulation"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0014-2999(02)02690-0","article-title":"Selective interaction of bile acids with muscarinic receptors: A case of molecular mimicry","volume":"457","author":"Raufman","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000064347","article-title":"Deoxycholic Acid Conjugates are Muscarinic Cholinergic Receptor Antagonists","volume":"65","author":"Raufman","year":"2002","journal-title":"Pharmacology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1124\/jpet.102.036376","article-title":"Lithocholylcholine, a bile acid\/acetylcholine hybrid, is a muscarinic receptor antagonist","volume":"303","author":"Cheng","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1152\/ajpcell.00514.2008","article-title":"Muscarinic receptors and ligands in cancer","volume":"296","author":"Shah","year":"2009","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ejphar.2005.05.037","article-title":"Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M3 receptor-dependent","volume":"517","author":"Khurana","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"7110","DOI":"10.1038\/s41598-018-25569-4","article-title":"Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: Role of Gi protein, muscarinic receptors and TGR5","volume":"8","author":"Ibrahim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Sheikh Abdul Kadir, S.H., Miragoli, M., Abu-Hayyeh, S., Moshkov A v Xie, Q., Keitel, V., Nikolaev, V.O., Williamson, C., and Gorelik, J. (2010). Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009689"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1085\/jgp.20028537","article-title":"Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca 2-activated K (BK Ca) Channel Activity in Smooth Muscle Cells","volume":"119","author":"Dopico","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1124\/mol.107.034330","article-title":"\u03b21 (KCNMB1) subunits mediate lithocholate activation of large-conductance Ca2+-activated K+ channels and dilation in small, resistance-size arteries","volume":"72","author":"Bukiya","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1136\/heartjnl-2013-304163","article-title":"Bile acids induce arrhythmias in human atrial myocardium-implications for altered serum bile acid composition in patients with atrial fibrillation","volume":"99","author":"Rainer","year":"2013","journal-title":"Heart"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Oniszczuk, A., Oniszczuk, T., Gancarz, M., Szym\u00e1 Nska, J., and Hamaguchi, M. (2021). Role of Gut Microbiota, Probiotics and Prebiotics in the Cardiovascular Diseases. Molecules, 26.","DOI":"10.3390\/molecules26041172"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"101504","DOI":"10.1016\/j.beem.2021.101504","article-title":"Next-generation therapeutic bacteria for treatment of obesity, diabetes, and other endocrine diseases","volume":"35","author":"Bui","year":"2021","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.clnu.2015.12.016","article-title":"Consuming yellow pea fiber reduces voluntary energy intake and body fat in overweight\/obese adults in a 12-week randomized controlled trial","volume":"36","author":"Lambert","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jnutbio.2018.11.003","article-title":"Impact of dietary fiber supplementation on modulating microbiota\u2013host\u2013metabolic axes in obesity","volume":"64","author":"Mayengbam","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"e1900797","DOI":"10.1002\/mnfr.201900797","article-title":"The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis","volume":"64","author":"Ramji","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1128\/AEM.72.3.1729-1738.2006","article-title":"Bile salt hydrolase activity in probiotics","volume":"72","author":"Begley","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"5993","DOI":"10.1007\/s00253-019-09927-4","article-title":"Updates in understanding the hypocholesterolemia effect of probiotics on atherosclerosis","volume":"103","author":"Hassan","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1016\/j.hlc.2021.09.006","article-title":"The Effects of Probiotics on Inflammation, Endothelial Dysfunction, and Atherosclerosis Progression: A Mechanistic Overview","volume":"31","author":"Salari","year":"2022","journal-title":"Heart Lung Circ."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Kim, K.T., Kim, J.W., Kim S il Kim, S., Nguyen, T.H., and Kang, C.H. (2021). Antioxidant and anti-inflammatory effect and probiotic properties of lactic acid bacteria isolated from canine and feline feces. Microorganisms, 9.","DOI":"10.3390\/microorganisms9091971"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3920\/BM2018.0028","article-title":"Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults","volume":"10","author":"Hibberd","year":"2019","journal-title":"Benef. Microbes"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Ghorbani, Z., Kazemi, A., UPBartolomaeus, T., Martami, F., Noormohammadi, M., Salari, A., L\u00f6ber, U., Balou, H.A., Forslund, S.K., and Mahdavi-Roshan, M. (2022). The effect of probiotic and synbiotic supplementation on lipid parameters among patients with cardiometabolic risk factors: A systematic review and meta-analysis of clinical trials. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvac128"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1007\/s00394-020-02248-7","article-title":"Effects of synbiotic consumption on lipid profile: A systematic review and meta-analysis of randomized controlled clinical trials","volume":"59","author":"Hadi","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1053\/j.gastro.2013.05.042","article-title":"Efficacy and safety of the farnesoid x receptor agonist Obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease","volume":"145","author":"Mudaliar","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/cpdd.34","article-title":"Safety, pharmacokinetics, and pharmacodynamic effects of a selective TGR5 Agonist, SB-756050, in Type 2 Diabetes","volume":"2","author":"Hodge","year":"2013","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1080\/13543776.2022.1994551","article-title":"TGR5 agonists for diabetes treatment: A patent review and clinical advancements (2012-present)","volume":"32","author":"Bhimanwar","year":"2022","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jcmgh.2020.12.004","article-title":"Cholangiopathy and Biliary Fibrosis in Cyp2c70-Deficient Mice Are Fully Reversed by Ursodeoxycholic Acid","volume":"11","author":"Palmiotti","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1194\/jlr.RA119000395","article-title":"Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition","volume":"61","author":"Honda","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1194\/jlr.RA119000307","article-title":"Of mice and men: Murine bile acids explain species differences in the regulation of bile acid and cholesterol metabolism","volume":"61","author":"Straniero","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/MCO.0000000000000709","article-title":"Emerging roles of bile acids in control of intestinal functions","volume":"24","author":"Yang","year":"2021","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Kritikou, E., Depuydt, M.A.C., de Vries, M.R., Mulder, K.E., Govaert, A.M., Smit, M.D., van Duijn, J., Foks, A.C., Wezel, A., and Smeets, H.J. (2019). Flow Cytometry-Based Characterization of mast Cells in Human Atherosclerosis. Cells, 8.","DOI":"10.3390\/cells8040334"},{"key":"ref_205","first-page":"e50542","article-title":"A human ex vivo atherosclerotic plaque model to study lesion biology","volume":"87","author":"Erbel","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.atherosclerosis.2017.10.003","article-title":"Ex vivo culture of human atherosclerotic plaques: A model to study immune cells in atherogenesis","volume":"267","author":"Lebedeva","year":"2017","journal-title":"Atherosclerosis"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/8\/1850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:14:25Z","timestamp":1760123665000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/8\/1850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,12]]},"references-count":206,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["nu15081850"],"URL":"https:\/\/doi.org\/10.3390\/nu15081850","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,12]]}}}