Department of Cardiology.
Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Coron Artery Dis. 2024 Sep 1;35(6):498-508. doi: 10.1097/MCA.0000000000001377. Epub 2024 May 17.
Inflammation and hyperlipidemia can cause atherosclerosis. Prebiotic inulin has been proven to effectively reduce inflammation and blood lipid levels. Utilizing a mouse model induced by a high-fat diet, this study aimed to explore whether the characteristic intestinal flora and its metabolites mediate the effects of inulin intervention on atherosclerosis and to clarify the specific mechanism.
Thirty apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into three groups. They were fed with a normal diet, a high-fat diet or an inulin+high-fat diet for 16 weeks. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the three groups were compared. The gross aorta and aortic sinus of mice were stained with oil red O, and the area of atherosclerotic plaque was observed and compared. The diversity and structure of the mouse fecal flora were detected by sequencing the V3-V4 region of the 16S rRNA gene, and the levels of metabolites in mouse feces were assessed by gas chromatography-mass spectrometry. The plasma lipopolysaccharide (LPS) levels and aortic inflammatory factors were measured by multi-index flow cytometry (CBA).
ApoE-/- mice fed with the high-fat diet exhibited an increase of approximately 46% in the area of atherosclerotic lesions, and the levels of TC, TG and LDL-C were significantly increased ( P < 0.05) compared with levels in the normal diet group. After inulin was added to the high-fat group, the area of atherosclerotic lesions, the level of serum LPS and aortic inflammation were reduced, and the levels of TC, TG and LDL-C were decreased ( P < 0.05). Based on 16S rRNA gene detection, we found that the composition of the intestinal microbiota, such as Prevotella, and metabolites, such as L-arginine, changed significantly due to hyperlipidemia, and the dietary inulin intervention partially reversed the relevant changes.
Inulin can inhibit the formation of atherosclerotic plaques, which may be related to the changes in lipid metabolism, the composition of the intestinal microbial community and its metabolites, and the inhibition of the expression of related inflammatory factors. Our study identified the relationships among the characteristic intestinal microbiota, metabolites and atherosclerosis, aiming to provide a new direction for future research to delay or treat atherosclerosis by changing the composition and function of the host intestinal microbiota and metabolites.
炎症和高血脂会导致动脉粥样硬化。研究表明，益生元菊粉可以有效降低炎症和血脂水平。本研究利用高脂饮食诱导的小鼠模型，旨在探讨特征性肠道菌群及其代谢产物是否介导菊粉干预对动脉粥样硬化的影响，并阐明具体机制。
30 只载脂蛋白 E 缺陷（ApoE-/-）小鼠随机分为三组，分别给予正常饮食、高脂饮食或菊粉+高脂饮食 16 周。比较三组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平。油红 O 染色各组小鼠的主动脉和主动脉窦，观察并比较动脉粥样硬化斑块面积。通过 16S rRNA 基因 V3-V4 区测序检测小鼠粪便菌群的多样性和结构，通过气相色谱-质谱联用技术检测小鼠粪便代谢物水平。通过多指标流式细胞术（CBA）检测血浆内毒素（LPS）水平和主动脉炎症因子。
高脂饮食喂养的 ApoE-/-小鼠的动脉粥样硬化病变面积增加约 46%，TC、TG 和 LDL-C 水平明显高于正常饮食组（P<0.05）。高脂组添加菊粉后，动脉粥样硬化病变面积、血清 LPS 水平和主动脉炎症减轻，TC、TG 和 LDL-C 水平降低（P<0.05）。基于 16S rRNA 基因检测，我们发现，由于高血脂，肠道微生物群的组成，如普雷沃氏菌，以及代谢物，如 L-精氨酸，发生了显著变化，而膳食菊粉干预部分逆转了相关变化。
菊粉可以抑制动脉粥样硬化斑块的形成，这可能与脂代谢变化、肠道微生物群落组成及其代谢物、相关炎症因子表达抑制有关。本研究确定了特征性肠道微生物群、代谢物与动脉粥样硬化之间的关系，旨在为通过改变宿主肠道微生物群和代谢物的组成和功能来延缓或治疗动脉粥样硬化提供新的研究方向。
