{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:22:41Z","timestamp":1790788961307,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672075"],"award-info":[{"award-number":["81672075"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7222156"],"award-info":[{"award-number":["7222156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7214250"],"award-info":[{"award-number":["7214250"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021-I2M-1-050"],"award-info":[{"award-number":["2021-I2M-1-050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFE0114200"],"award-info":[{"award-number":["2021YFE0114200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["81672075"],"award-info":[{"award-number":["81672075"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7222156"],"award-info":[{"award-number":["7222156"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7214250"],"award-info":[{"award-number":["7214250"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["2021-I2M-1-050"],"award-info":[{"award-number":["2021-I2M-1-050"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"the Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["2021YFE0114200"],"award-info":[{"award-number":["2021YFE0114200"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["81672075"],"award-info":[{"award-number":["81672075"]}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["7222156"],"award-info":[{"award-number":["7222156"]}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["7214250"],"award-info":[{"award-number":["7214250"]}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-050"],"award-info":[{"award-number":["2021-I2M-1-050"]}]},{"name":"the CAMS Innovation Fund for Medical Sciences","award":["2021YFE0114200"],"award-info":[{"award-number":["2021YFE0114200"]}]},{"DOI":"10.13039\/501100012166","name":"the National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["81672075"],"award-info":[{"award-number":["81672075"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"the National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["7222156"],"award-info":[{"award-number":["7222156"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"the National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["7214250"],"award-info":[{"award-number":["7214250"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"the National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2021-I2M-1-050"],"award-info":[{"award-number":["2021-I2M-1-050"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"the National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2021YFE0114200"],"award-info":[{"award-number":["2021YFE0114200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Atherosclerosis (AS) is a chronic inflammatory disease that serves as a common pathogenic underpinning for various cardiovascular diseases. Although high circulating branched-chain amino acid (BCAA) levels may represent a risk factor for AS, it is unclear whether dietary BCAA supplementation causes elevated levels of circulating BCAAs and hence influences AS, and the related mechanisms are not well understood. Here, ApoE-deficient mice (ApoE\u2212\/\u2212) were fed a diet supplemented with or without BCAAs to investigate the effects of BCAAs on AS and determine potential related mechanisms. In this study, compared with the high-fat diet (HFD), high-fat diet supplemented with BCAAs (HFB) reduced the atherosclerotic lesion area and caused a significant decrease in serum cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. BCAA supplementation suppressed the systemic inflammatory response by reducing macrophage infiltration; lowering serum levels of inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2) and interleukin-6 (IL-6); and suppressing inflammatory related signaling pathways. Furthermore, BCAA supplementation altered the gut bacterial beta diversity and composition, especially reducing harmful bacteria and increasing probiotic bacteria, along with increasing bile acid (BA) excretion. In addition, the levels of total BAs, primary BAs, 12\u03b1-hydroxylated bile acids (12\u03b1-OH BAs) and non-12\u03b1-hydroxylated bile acids (non-12\u03b1-OH BAs) in cecal and colonic contents were increased in the HFB group of mice compared with the HFD group. Overall, these data indicate that dietary BCAA supplementation can attenuate atherosclerosis induced by HFD in ApoE\u2212\/\u2212 mice through improved dyslipidemia and inflammation, mechanisms involving the intestinal microbiota, and promotion of BA excretion.<\/jats:p>","DOI":"10.3390\/nu14235065","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:38:49Z","timestamp":1669621129000},"page":"5065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Oral Administration of Branched-Chain Amino Acids Attenuates Atherosclerosis by Inhibiting the Inflammatory Response and Regulating the Gut Microbiota in ApoE-Deficient Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1494-194X","authenticated-orcid":false,"given":"Ziyun","family":"Li","sequence":"first","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongna","family":"Mu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenduo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zeng","sequence":"additional","affiliation":[{"name":"National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, National Center of Gerontology, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siming","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"},{"name":"National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, National Center of Gerontology, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Dong","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6728","authenticated-orcid":false,"given":"Ruiyue","family":"Yang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital\/National Center of Gerontology of National Health Commission, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1161\/CIRCRESAHA.118.313816","article-title":"Atherosclerosis: A chronic inflammatory disease with an autoimmune component","volume":"123","author":"Kobiyama","year":"2018","journal-title":"Circ. Res."},{"key":"ref_3","first-page":"e984","article-title":"Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association","volume":"143","author":"Poirier","year":"2021","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nrcardio.2017.154","article-title":"Epidemiology of cardiovascular disease in young individuals","volume":"15","author":"Andersson","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","first-page":"e38","article-title":"Heart disease and stroke statistics-2016 update a report from the American Heart Association","volume":"133","author":"Benjamin","year":"2017","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1161\/CIRCRESAHA.110.223875","article-title":"Oxidation-Specific Epitopes Are Danger-Associated Molecular Patterns Recognized by Pattern Recognition Receptors of Innate Immunity","volume":"108","author":"Miller","year":"2011","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1194\/jlr.R400001-JLR200","article-title":"Thematic review series: The Pathogenesis of Atherosclerosis The oxidation hypothesis of atherogenesis: The role of oxidized phospholipids and HDL","volume":"45","author":"Navab","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/CIRCRESAHA.118.313591","article-title":"Immunity and Inflammation in Atherosclerosis","volume":"124","author":"Wolf","year":"2019","journal-title":"Circ. Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Xian, X., Wang, Z., Bi, Y., Chen, Q., Han, X., Tang, D., and Chen, R. (2018). Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules, 8.","DOI":"10.3390\/biom8030080"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1042\/CS20180306","article-title":"Atherosclerosis and inflammation: Overview and updates","volume":"132","author":"Geovanini","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1001\/archinte.167.2.174","article-title":"Psychosocial Factors and Inflammation in the Multi-Ethnic Study of Atherosclerosis","volume":"167","author":"Ranjit","year":"2007","journal-title":"Arch. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.mehy.2007.05.030","article-title":"TLRs are important inflammatory factors in atherosclerosis and may be a therapeutic target","volume":"70","author":"Liu","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","unstructured":"Sanchez-Rodriguez, E., Egea-Zorrilla, A., Plaza-D\u00edaz, J., Arag\u00f3n-Vela, J., Mu\u00f1oz-Quezada, S., Tercedor-S\u00e1nchez, L., and Abadia-Molina, F. (2020). The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related Cardiovascular Diseases. Nutrients, 12.","DOI":"10.3390\/nu12030605"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.atherosclerosis.2017.11.023","article-title":"Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe\u2212\/\u2212 mice","volume":"268","author":"Zhu","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1074\/jbc.M114.618249","article-title":"Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation","volume":"290","author":"Gregory","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1097\/CM9.0000000000000696","article-title":"Gut microbiota and metabolic syndrome","volume":"133","author":"Wang","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.tem.2017.11.002","article-title":"Role of Bile Acids in Metabolic Control","volume":"29","author":"Molinaro","year":"2018","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41575-021-00566-7","article-title":"Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology","volume":"19","author":"Fuchs","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.molmed.2015.09.001","article-title":"Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders","volume":"21","author":"Fiorucci","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1080\/07853890.2021.1965204","article-title":"Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease","volume":"53","author":"Hu","year":"2021","journal-title":"Ann. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e002157","DOI":"10.1161\/CIRCGEN.118.002157","article-title":"Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women","volume":"11","author":"Tobias","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12944-016-0291-7","article-title":"The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population","volume":"15","author":"Yang","year":"2016","journal-title":"Lipids Health Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1373\/clinchem.2015.251710","article-title":"Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial","volume":"62","author":"Toledo","year":"2016","journal-title":"Clin. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e0022","DOI":"10.5041\/RMMJ.10337","article-title":"Specific Amino Acids Affect Cardiovascular Diseases and Atherogenesis via Protection against Macrophage Foam Cell Formation: Review Article","volume":"9","author":"Aviram","year":"2018","journal-title":"Rambam. Maimonides Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"920277","DOI":"10.3389\/fmicb.2022.920277","article-title":"Oral administration of branched-chain amino acids ameliorates high-fat diet-induced metabolic-associated fatty liver disease via gut microbiota-associated mechanisms","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jchromb.2015.12.019","article-title":"Simultaneous quantification of cardiovascular disease related metabolic risk factors using liquid chromatography tandem mass spectrometry in human serum","volume":"1009\u20131010","author":"Wang","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/aps.2015.88","article-title":"Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice","volume":"37","author":"Zhao","year":"2016","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s10103-007-0535-x","article-title":"Evaluation of collagen in atherosclerotic plaques: The use of two coherent laser-based imaging methods","volume":"24","author":"Nadkarni","year":"2009","journal-title":"Lasers Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/ATVBAHA.121.316233","article-title":"Crosstalk Between Macrophages and Vascular Smooth Muscle Cells in Atherosclerotic Plaque Stability","volume":"42","author":"Yurdagul","year":"2022","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1111\/bph.14779","article-title":"The role of smooth muscle cells in plaque stability: Therapeutic targeting potential","volume":"176","author":"Harman","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10439-013-0888-1","article-title":"Biomechanics of Atherosclerotic Coronary Plaque: Site, Stability and In Vivo Elasticity Modeling","volume":"42","author":"Ohayon","year":"2014","journal-title":"Ann. Biomed. Eng."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.freeradbiomed.2019.03.036","article-title":"An update on lipid oxidation and inflammation in cardiovascular diseases","volume":"144","author":"Zhong","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel","volume":"38","author":"Ference","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.jacl.2019.09.002","article-title":"Association between dyslipidemia and plasma levels of branched-chain amino acids in the Japanese population without diabetes mellitus","volume":"13","author":"Fukushima","year":"2019","journal-title":"J. Clin. Lipidol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/biof.1415","article-title":"Leucine supplementation attenuates macrophage foam-cell formation: Studies in humans, mice, and cultured macrophages","volume":"44","author":"Rom","year":"2018","journal-title":"BioFactors"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB Signaling: Navigating the Network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"ref_40","first-page":"322","article-title":"LncRNA H19 promotes atherosclerosis by regulating MAPK and NF-kB signaling pathway","volume":"21","author":"Pan","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e140627","DOI":"10.1172\/jci.insight.140627","article-title":"LncRNA VINAS regulates atherosclerosis by modulating NF-\u03baB and MAPK signaling","volume":"5","author":"Simion","year":"2020","journal-title":"JCI Insight"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1038\/s41467-019-09588-x","article-title":"Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK-NF-\u03baB signaling mediated inflammation","volume":"10","author":"Ben","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor NF-kappaB pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1161\/CIRCRESAHA.121.319077","article-title":"Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease","volume":"128","author":"Ridker","year":"2021","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.yexcr.2015.05.023","article-title":"MicroRNA-101 overexpression by IL-6 and TNF-\u03b1 inhibits cholesterol efflux by suppressing ATP-binding cassette transporter A1 expression","volume":"336","author":"Zhang","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.yjmcc.2014.02.012","article-title":"TNF-\u03b1 promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: Crosstalk between NF-\u03baB and PPAR-\u03b3","volume":"72","author":"Zhang","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1093\/eurheartj\/ehy128","article-title":"Interleukin-1 blockade in cardiovascular diseases: A clinical update","volume":"39","author":"Buckley","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_48","first-page":"217","article-title":"Blocking interleukin-1 as a novel therapeutic strategy for secondary prevention of cardiovascular events","volume":"26","author":"Abbate","year":"2012","journal-title":"BioDrugs Clin. Immunother. Biopharm. Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/CIRCRESAHA.118.311362","article-title":"NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis","volume":"122","author":"Grebe","year":"2018","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1161\/01.ATV.16.8.1000","article-title":"Holt CM, Interleukin-1 beta in coronary arteries of patients with ischemic heart disease","volume":"16","author":"Galea","year":"1996","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1161\/01.ATV.19.6.1518","article-title":"Monocyte Chemoattractant Protein-1 Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice","volume":"19","author":"Aiello","year":"1999","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31304","DOI":"10.3402\/fnr.v60.31304","article-title":"Chronic leucine supplementation improves lipid metabolism in C57BL\/6J mice fed with a high-fat\/cholesterol diet","volume":"60","author":"Jiao","year":"2016","journal-title":"Food Nutr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"710","DOI":"10.2174\/1389201020666191105154619","article-title":"The Anti-Inflammatory Effects of Anacardic Acid on a TNF-\u03b1\u2014Induced Human Saphenous Vein Endothelial Cell Culture Model","volume":"21","author":"Demir","year":"2020","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.nutres.2020.03.003","article-title":"Arctium lappa root extract containing L-arginine prevents TNF-\u03b1-induced early atherosclerosis in vitro and in vivo","volume":"77","author":"Lee","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1161\/CIRCULATIONAHA.119.043581","article-title":"Branched-Chain Amino Acid Catabolism Promotes Thrombosis Risk by Enhancing Tropomodulin-3 Propionylation in Platelets","volume":"142","author":"Xu","year":"2020","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12986-018-0271-1","article-title":"Branched-chain amino acids in health and disease: Metabolism, alterations in blood plasma, and as supplements","volume":"15","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1373\/clinchem.2017.285841","article-title":"Dietary Intakes and Circulating Concentrations of Branched-Chain Amino Acids in Relation to Incident Type 2 Diabetes Risk Among High-Risk Women with a History of Gestational Diabetes Mellitus","volume":"64","author":"Tobias","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"14513","DOI":"10.1021\/acs.jafc.0c06138","article-title":"3\u2032-Hydroxydaidzein Improves Obesity Through the Induced Browning of Beige Adipose and Modulation of Gut Microbiota in Mice with Obesity Induced by a High-Fat Diet","volume":"68","author":"Tung","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fmicb.2015.00155","article-title":"The genus Weissella: Taxonomy, ecology and biotechnological potential","volume":"6","author":"Fusco","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hiraishi, K., Zhao, F., Kurahara, L.-H., Li, X., Yamashita, T., Hashimoto, T., Matsuda, Y., Sun, Z., Zhang, H., and Hirano, K. (2022). Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis. Nutrients, 14.","DOI":"10.3390\/nu14030649"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ijbiomac.2021.12.042","article-title":"Protective effects of polysaccharides from Atractylodes macrocephalae Koidz. against dextran sulfate sodium induced intestinal mucosal injury on mice","volume":"195","author":"Kai","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1042\/CS20180087","article-title":"Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure","volume":"132","author":"Kim","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1128\/JCM.00987-11","article-title":"Desulfovibrio desulfuricans Bacteremia in an Immunocompromised Host with a Liver Graft and Ulcerative Colitis","volume":"50","author":"Verstreken","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41398-021-01428-1","article-title":"Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment","volume":"11","author":"Duan","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1017\/S0029665120000051","article-title":"Nutritional prevention of colorectal cancer","volume":"80","author":"Hull","year":"2021","journal-title":"Proc. Nutr. Soc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1093\/jn\/128.7.1199","article-title":"Dietary Psyllium Increases Fecal Bile Acid Excretion, Total Steroid Excretion and Bile Acid Biosynthesis in Rats","volume":"128","author":"Buhman","year":"1998","journal-title":"J. Nutr."},{"key":"ref_67","first-page":"E121","article-title":"Cyp8b1 ablation prevents Western diet-induced weight gain and hepatic steatosis because of impaired fat absorption","volume":"313","author":"Bertaggia","year":"2017","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.cmet.2015.02.004","article-title":"A Liver-Enriched Long Non-Coding RNA, lncLSTR, Regulates Systemic Lipid Metabolism in Mice","volume":"21","author":"Li","year":"2015","journal-title":"Cell Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.2337\/db13-0639","article-title":"Human Insulin Resistance Is Associated With Increased Plasma Levels of 12\u03b1-Hydroxylated Bile Acids","volume":"62","author":"Haeusler","year":"2013","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zeng, H., Umar, S., Rust, B., Lazarova, D., and Bordonaro, M. (2019). Secondary Bile Acids and Short Chain Fatty Acids in the Colon: A Focus on Colonic Microbiome, Cell Proliferation, Inflammation, and Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051214"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eaax6208","DOI":"10.1126\/sciadv.aax6208","article-title":"Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism","volume":"6","author":"Zeng","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s12272-017-0931-0","article-title":"Effect of decreased BCAA synthesis through disruption of ilvC gene on the virulence of Streptococcus pneumoniae","volume":"40","author":"Kim","year":"2017","journal-title":"Arch. Pharmacal Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e02210-15","DOI":"10.1128\/mBio.02210-15","article-title":"Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota","volume":"7","author":"Chen","year":"2016","journal-title":"mBio"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Liang, J., Kou, S., Chen, C., Raza, S.H.A., Wang, S., Ma, X., Zhang, W.-J., and Nie, C. (2021). Effects of Clostridium butyricum on growth performance, metabonomics and intestinal microbial differences of weaned piglets. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02143-z"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-G\u00f3mez, J.G., L\u00f3pez-Bonilla, A., Trejo-Tapia, G., \u00c1vila-Reyes, S.V., Jim\u00e9nez-Aparicio, A.R., and Hern\u00e1ndez-S\u00e1nchez, H. (2021). In Vitro Bile Salt Hydrolase (BSH) Activity Screening of Different Probiotic Microorganisms. Foods, 10.","DOI":"10.3390\/foods10030674"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.3168\/jds.S0022-0302(99)75506-2","article-title":"Screening of Lactic Acid Bacteria for Bile Salt Hydrolase Activity","volume":"82","author":"Tanaka","year":"1999","journal-title":"J. Dairy Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/23\/5065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:28:30Z","timestamp":1760146110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/23\/5065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":76,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["nu14235065"],"URL":"https:\/\/doi.org\/10.3390\/nu14235065","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]}}}