Dietary astaxanthin-rich extract ameliorates atherosclerosis/retinopathy and restructures gut microbiome in apolipoprotein E-deficient mice fed on a high-fat diet

Scope: Atherosclerosis (AS) is the leading cause of ischemic disease. However, the anti-AS effects of astaxanthin and its potential mechanisms remain unclear. This study is aimed to investigate the function of astaxanthin-rich extract (ASTE) on AS and gut microbiota as well as the difference from atorvastatin (ATO) in apolipoprotein E-deficient (ApoE-/-) mice. Methods and results: Wild type (WT) and ApoE-/- mice were divided into seven groups: the low-fat diet (LFD) and high-fat diet (HFD) groups (in both types) as well as three ApoE-/- groups based on HFD added with two doses of ASTE and one dose of ATO, respectively. After 30 weeks of intervention, results showed that ASTE significantly inhibited body weight increase, lipids accumulation in serum/liver, and AS-lesions in the aorta. Furthermore, fundus fluorescein angiography and retinal CD31 immunohistochemical staining showed that ASTE could alleviate the occurrence of AS-retinopathy. H&E staining showed that ASTE could protect the colon's mucosal epithelium from damage. The gas chromatographic and gene expression analyses showed that ASTE promoted the excretion of fecal acidic and neutral sterols from cholesterol by increasing LXRα, CYP7A1, and ABCG5/8 and decreasing FXR, NPC1L1, ACAT2, and MTTP expressions. Remarkably, the ASTE administration maintained the gut barrier by enhancing gene expression of JAM-A, Occludin, and mucin2 in the colon and reshaped gut microbiota with the feature of blooming Akkermansia. Conclusion: Our results suggested that ASTE could prevent AS in both macrovascular and/or microvascular as well as used as novel prebiotics by supporting the bile acid excretion and growth of Akkermansia.