Abstract
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 Apolipoprotein E (ApoE)−/− mice. In the initial portion, the ApoE−/− 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 ApoE−/− 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 in situ macrophages (Mψs) 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 ApoE−/− mice via the gut microbiota-inflammation-artery axis.
Highlights
Atherosclerosis (AS), characterized by excessive cholesterol deposition within the artery wall, is the leading cause of cardiovascular diseases (CVD) including coronary heart disease, cerebral infarction myocardial infarction (MI), stroke, and peripheral vascular disease [1], accounting for a major cause of mortality and morbidity in the world [2, 3]
The results showed that high-fat diet (HFD) decreased the amounts of acetic acid, propionic acid, and valeric acid (Figures 4C–G) compared to the control group (CON) group; whereas the amounts of acetic acid, propionic acid, isovaleric acid, isobutyric acid, and valeric acid were increased after flaxseed oil (FO) treatment, compared with the model group (MOD) group (Figures 4C–G)
We found that the FO administration inhibited the occurrence of inflammation and LPS in AS, related to the disturbance of gut microbiota and microbial metabolites short-chain fatty acids (SCFAs)/bile acids (BAs), as well as intestinal barrier function
Summary
Atherosclerosis (AS), characterized by excessive cholesterol deposition within the artery wall, is the leading cause of cardiovascular diseases (CVD) including coronary heart disease, cerebral infarction myocardial infarction (MI), stroke, and peripheral vascular disease [1], accounting for a major cause of mortality and morbidity in the world [2, 3]. AS represents a chronic inflammatory disorder of the vascular wall involving many circulating immune cells, such as monocytes, lymphocytes, and platelets [4]. The monocyte infiltration and the subsequent formation of macrophages (Mψs)-derived foam cells for the release of pro-inflammatory cytokines are crucial in the progression of AS [1, 5, 6]. Monocytes are rich in cell-activating, oxidized, and low-density lipoprotein (oxLDL) in accumulating the development of lesions and forming the early plaques (known as fatty streaks) on the intima [7]. The AS changes from fatty streaks to plaque rupture as well as thrombosis. Due to limited dietary management of AS, some novel strategies are urgently needed
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