Center for the Prevention of Cardiovascular Disease, Department of Medicine, New York University School of Medicine, New York, USA.
Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, USA.
Sci Rep. 2021 Apr 26;11(1):8966. doi: 10.1038/s41598-021-88479-y.
Since alterations in the intestinal microbiota may induce systemic inflammation and polarization of macrophages to the M1 state, the microbiome role in atherosclerosis, an M1-driven disease, requires evaluation. We aimed to determine if antibiotic (Abx) induced alterations to the intestinal microbiota interferes with atherosclerotic plaque inflammation resolution after lipid-lowering in mice. Hyperlipidemic Apoe mice were fed a western diet to develop aortic atherosclerosis with aortas then transplanted into normolipidemic wild-type (WT) mice to model clinically aggressive lipid management and promote atherosclerosis inflammation resolution. Gut microbial composition pre and post-transplant was altered via an enteral antibiotic or not. Post aortic transplant, after Abx treatment, while plaque size did not differ, compared to Apoe mice, Abx WT recipient mice had a 32% reduction in CD68-expressing cells (p = 0.02) vs. a non-significant 12% reduction in Abx WT mice. A trend toward an M1 plaque CD68-expresing cell phenotype was noted in Abx mice. By 16S rRNA sequence analysis, the Abx mice had reduced alpha diversity and increased Firmicutes/Bacteroidetes relative abundance ratio with a correlation between gut Firmicutes abundance and plaque CD68-expressing cell content (p < 0.05). These results indicate that in a murine atherosclerotic plaque inflammation resolution model, antibiotic-induced microbiome perturbation may blunt the effectiveness of lipid-lowering to reduce the content of plaque inflammatory CD68-expressing cells.
由于肠道微生物群的改变可能会引起全身炎症和巨噬细胞向 M1 状态的极化，因此需要评估微生物组在动脉粥样硬化（一种 M1 驱动的疾病）中的作用。我们旨在确定降脂后抗生素（Abx）诱导的肠道微生物群改变是否会干扰小鼠动脉粥样硬化斑块炎症的消退。高脂血症 Apoe 小鼠喂食西式饮食以发展主动脉粥样硬化，然后将主动脉移植到正常脂质野生型（WT）小鼠中，以模拟临床上积极的脂质管理并促进动脉粥样硬化炎症的消退。通过肠内抗生素或不改变移植前和移植后的肠道微生物组成。在接受 Abx 治疗后进行主动脉移植后，与 Apoe 小鼠相比，Abx WT 受体小鼠的 CD68 表达细胞减少了 32%（p=0.02），而非 Abx WT 小鼠的 CD68 表达细胞减少了 12%，但无统计学意义。在 Abx 小鼠中观察到 M1 斑块 CD68 表达细胞表型呈趋势。通过 16S rRNA 序列分析，Abx 小鼠的 alpha 多样性降低，厚壁菌门/拟杆菌门相对丰度比值增加，并且肠道厚壁菌门丰度与斑块 CD68 表达细胞含量之间存在相关性（p<0.05）。这些结果表明，在小鼠动脉粥样硬化斑块炎症消退模型中，抗生素诱导的微生物群改变可能会削弱降脂降低斑块炎症性 CD68 表达细胞含量的效果。
