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Cardiovasc. Med."],"abstract":"<jats:p>Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic <jats:italic>Apolipoprotein E<\/jats:italic> (<jats:italic>ApoE<\/jats:italic>)<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In the initial portion, the <jats:italic>ApoE<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD\/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated <jats:italic>ApoE<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice were divided into two groups: AB-treated model group (AB\/MOD) and FO-fed AB-treated model group (AB\/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic\/vascular inflammatory cytokines and <jats:italic>in situ<\/jats:italic> macrophages (M\u03c8s) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in <jats:italic>ApoE<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice <jats:italic>via<\/jats:italic> the gut microbiota-inflammation-artery axis.<\/jats:p>","DOI":"10.3389\/fcvm.2022.830781","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T04:44:11Z","timestamp":1646023451000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Dietary \u03b1-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE\u2212\/\u2212 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