{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:49:18Z","timestamp":1792212558153,"version":"4.4.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO. 81873130, NO. 81573733, NO. 81804025"],"award-info":[{"award-number":["NO. 81873130, NO. 81573733, NO. 81804025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010229","name":"Natural Science Foundation of Tianjin Municipal Science and Technology Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Aging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the underlying mechanism of how aging aggravates AS advancement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A young (five-week-old, YM) and aged group (32-week-old, OM) male apoE<jats:sup>-\/-<\/jats:sup> mice with a high fat diet were used as models, and age-matched male wild-type C57BL\/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ApoE<jats:sup>-\/-<\/jats:sup> mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE<jats:sup>-\/-<\/jats:sup> mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal\u00a0flora composition among the four groups, and harmful bacteria such as <jats:italic>Lachnospiraceae_FCS020<\/jats:italic>, <jats:italic>Ruminococcaceae_UCG-009<\/jats:italic>, <jats:italic>Acetatifactor<\/jats:italic>, <jats:italic>Lachnoclostridium<\/jats:italic> and <jats:italic>Lactobacillus_gasseri<\/jats:italic> were significantly increased in the aged apoE<jats:sup>-\/-<\/jats:sup> mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2\u03b1, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Aging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal\u00a0flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2021.618265","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T06:17:36Z","timestamp":1616048256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":72,"title":["The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis"],"prefix":"10.3389","volume":"11","author":[{"given":"Yingxin","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danbin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yefei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maojuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huhu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"B45","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/s0165-2478(02)00228-6","article-title":"Recognition of pathogen-associated molecular patterns by TLR family","volume":"85","author":"Akira","year":"2003","journal-title":"Immunol. Lett."},{"key":"B3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41569-019-0169-2","article-title":"Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities","volume":"16","author":"B\u00e4ck","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"B11","doi-asserted-by":"publisher","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":"B28","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.arr.2017.09.001","article-title":"Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition","volume":"40","author":"Calder","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1039\/c6fo01532h","article-title":"Dietary Fibre-Based Scfa Mixtures Promote Both Protection and Repair of Intestinal Epithelial Barrier Function in a Caco-2 Cell Model","volume":"8","author":"Chen","year":"2017","journal-title":"Food Funct."},{"key":"B58","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.cmet.2014.09.004","article-title":"The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism","volume":"20","author":"Demetz","year":"2014","journal-title":"Cell Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: highly accurate OTU sequences from microbial amplicon reads","volume":"10","author":"Edgar","year":"2013","journal-title":"Nat. Methods"},{"key":"B33","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1111\/joim.12584","article-title":"Roles of the Gut in the Metabolic Syndrome: An Overview","author":"Fandriks","year":"2017","journal-title":"J. Intern. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1097\/MOL.0b013e32834a9790","article-title":"Cytochrome P450-dependent eicosanoid production and crosstalk","volume":"22","author":"Fleming","year":"2011","journal-title":"Curr. Opin. Lipidol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01385","article-title":"Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice","volume":"8","author":"Fransen","year":"2017","journal-title":"Front. Immunol."},{"key":"B10","doi-asserted-by":"publisher","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":"B34","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1097\/HCO.0000000000000720","article-title":"Gut microbiome and cardiovascular disease","volume":"35","author":"Herrema","year":"2020","journal-title":"Curr. Opin. Cardiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.cmet.2012.10.007","article-title":"Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk","volume":"16","author":"Holmes","year":"2012","journal-title":"Cell Metab."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1007\/s10096-019-03549-4","article-title":"Targeting Gut Microbiota as a Possible Therapy for Mastitis","volume":"38","author":"Hu","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1159\/000492571","article-title":"The Effects of Endurance Exercise and Diet on Atherosclerosis in Young and Aged ApoE-\/- and Wild-Type Mice","volume":"65","author":"Jakic","year":"2019","journal-title":"Gerontology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.jstrokecerebrovasdis","article-title":"Influence of Age Ranges on Relationship of Complex Aortic Plaque With Cervicocephalic Atherosclerosis in Ischemic Stroke","volume":"28","author":"Kong","year":"2019","journal-title":"J. Stroke Cerebrovasc. Diseases"},{"key":"B36","doi-asserted-by":"publisher","first-page":"4592","DOI":"10.1073\/pnas.1011383107","article-title":"Human Oral, Gut, and Plaque Microbiota in Patients with Atherosclerosis","author":"Koren","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.pharmthera.2018.08.012","article-title":"Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis","volume":"193","author":"Lacy","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1093\/eurheartj\/ehaa099","article-title":"Targeting cardiovascular inflammation: next steps in clinical translation","volume":"42","author":"Lawler","year":"2020","journal-title":"Eur. Heart J."},{"key":"B54","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1096\/fj.15-275487","article-title":"Lipoxin and resolvin biosynthesis is dependent on 5-lipoxygenase activating protein","volume":"29","author":"Lehmann","year":"2015","journal-title":"FASEB J."},{"key":"B46","doi-asserted-by":"publisher","first-page":"761","DOI":"10.4049\/jimmunol.1601416","article-title":"TLR9 Regulates the NF-\u03baB-NLRP3-IL-1\u03b2 Pathway Negatively in Salmonella-Induced NKG2D-Mediated Intestinal Inflammation","volume":"199","author":"Li","year":"2017","journal-title":"J. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ejphar.2018.05.003","article-title":"Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells","volume":"831","author":"Li","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1016\/j.jacc.2018.08.1043","article-title":"Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week","volume":"72","author":"Libby","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.atherosclerosis.2017.06.016","article-title":"Bacterial profile in human atherosclerotic plaques","volume":"263","author":"Lindskog Jonsson","year":"2017","journal-title":"Atherosclerosis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1161\/01.ATV.0000128849.12617.f4","article-title":"Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress","volume":"24","author":"Meir","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-9-r79","article-title":"Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment","volume":"13","author":"Morgan","year":"2012","journal-title":"Genome Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1161\/01.atv.14.1.133","article-title":"ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree","volume":"14","author":"Nakashima","year":"1994","journal-title":"Arterioscler. Thromb."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/srep16148","article-title":"The effect of short-chain fatty acids on human monocyte-derived dendritic cells","volume":"5","author":"Nastasi","year":"2015","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1161\/CIRCRESAHA.111.246876","article-title":"The intersection between aging and cardiovascular disease","volume":"110","author":"North","year":"2012","journal-title":"Circ. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.humimm.2019.05.001","article-title":"M1-Macrophage Polarization Is Upregulated in Deep Vein Thrombosis and Contributes to the Upregulation of Adhesion Molecules","volume":"80","author":"Pang","year":"2019","journal-title":"Hum. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1034\/j.1600-0838.2003.20218.x","article-title":"Possible Beneficial Role of Exercise in Modulating Low-Grade Inflammation in the elderly","volume":"13","author":"Pedersen","year":"2003","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"B17","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/0092-8674(92)90362-g","article-title":"Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells","volume":"71","author":"Plump","year":"1992","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.ijcard.2012.09.047","article-title":"Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis","volume":"168","author":"Ras","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nature13683","article-title":"Inflammatory caspases are innate immune receptors for intracellular LPS","volume":"514","author":"Shi","year":"2014","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"698","DOI":"10.2174\/1570161111666131219094045","article-title":"Cellular Senescence in Ageing, Age-Related Disease and Longevity","volume":"12","author":"Sikora","year":"2014","journal-title":"Curr. Vasc. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science","article-title":"The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3180","DOI":"10.1021\/acs.jproteome.7b00168","article-title":"Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction","volume":"16","author":"Song","year":"2017","journal-title":"J. Proteome Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1161\/CIRCRESAHA.117.309715","article-title":"Gut microbiota in cardiovascular health and disease","volume":"120","author":"Tang","year":"2017","journal-title":"Circ. Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1039\/c7fo01302g","article-title":"Effects of polysaccharides from purple sweet potatoes on immune response and gut microbiota composition in normal and cyclophosphamide treated mice","volume":"9","author":"Tang","year":"2018","journal-title":"Food Funct."},{"key":"B39","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/imm.12638","article-title":"High-density lipoprotein reduces inflammation from cholesterol crystals by inhibiting inflammasome activation","volume":"149","author":"Thacker","year":"2016","journal-title":"Immunology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1093\/eurheartj\/ehz919","article-title":"Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis","volume":"41","author":"Thum","year":"2020","journal-title":"Eur. Heart J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"E5934","DOI":"10.1073\/pnas.1612559113","article-title":"High-Fat Diet Modifies the Ppar-Gamma Pathway Leading to Disruption of Microbial and Physiological Ecosystem in Murine Small Intestine","volume":"113","author":"Tomas","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B1","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1161\/CIRCULATIONAHA.118.034326","article-title":"Oxidized Low-Density Lipoprotein Receptor in Lymphocytes Prevents AS and Predicts Subclinical Disease","volume":"139","author":"Tsilingiri","year":"2019","journal-title":"Circulation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.arr.2017.01.001","article-title":"Gut Microbiota: A Player in Aging and a Target for Anti-Aging Intervention","volume":"35","author":"Vaiserman","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00024","article-title":"Gut Microbiome and Serum Metabolome Analyses Identify Unsaturated Fatty Acids and Butanoate Metabolism Induced by Gut Microbiota in Patients With Chronic Spontaneous Urticaria","volume":"10","author":"Wang","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.chroma.2015.02.059","article-title":"Determining cyclooxygenase-2 activity in three different test systems utilizing online-solid phase extraction-liquid chromatography-mass spectrometry for parallel quantification of prostaglandin E (2), D (2) and thromboxane B (2)","volume":"1391","author":"Willenberg","year":"2015","journal-title":"J. Chromatogr. A."},{"key":"B38","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.cmet.2016.01.003","article-title":"The Intestinal Immune System in Obesity and Insulin Resistance","volume":"23","author":"Winer","year":"2016","journal-title":"Cell Metab."},{"key":"B57","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12967-017-1171-2","article-title":"Longitudinal analysis of serum oxylipin profile as a novel descriptor of the inflammatory response to surgery","volume":"15","author":"Wolfer","year":"2017","journal-title":"J. Transl. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1007\/s12035-017-0435-4","article-title":"Physiological and Pathological Roles of 15-Deoxy-\u039412,14-Prostaglandin J2 in the Central Nervous System and Neurological Diseases","volume":"55","author":"Yagami","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s00394-019-01928-3","article-title":"Reduced meal frequency alleviates high-fat diet-induced lipid accumulation and inflammation in adipose tissue of pigs under the circumstance of fixed feed allowance","volume":"59","author":"Yan","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"B26","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.plipres.2018.12.002","article-title":"Cholesterol transport system: An integrated cholesterol transport model involved in atherosclerosis","volume":"73","author":"Yu","year":"2018","journal-title":"Prog. Lipid Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1007\/s10522-019-09830-5","article-title":"Short-term dietary restriction in old mice rejuvenates the aging-induced structural imbalance of gut microbiota","volume":"20","author":"Zeng","year":"2019","journal-title":"Biogerontology"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.ijbiomac.2019.11.159","article-title":"An orally administered butyrate-releasing xylan derivative reduces inflammation in dextran sulphate sodium-induced murine colitis","volume":"156","author":"Zha","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/ismej.2009.112","article-title":"Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice","volume":"4","author":"Zhang","year":"2010","journal-title":"ISME J."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042529","article-title":"Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats","volume":"7","author":"Zhang","year":"2012","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00284","article-title":"Trained Immunity: An Underlying Driver of Inflammatory Atherosclerosis","volume":"11","author":"Zhong","year":"2020","journal-title":"Front. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1017\/S0007114515002159","article-title":"Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic plaque formation in apoE-deficient mice","volume":"114","author":"Zhou","year":"2015","journal-title":"Br. J. Nutr."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.618265\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T06:17:39Z","timestamp":1616048259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.618265\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":62,"alternative-id":["10.3389\/fcimb.2021.618265"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.618265","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"article-number":"618265"}}