Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Front Cell Infect Microbiol. 2021 Jul 1;11:560201. doi: 10.3389/fcimb.2021.560201. eCollection 2021.
Chronic intermittent hypoxia (CIH) is the prominent signature of highly prevalent obstructive sleep apnea (OSA) pathophysiology, which leads to increased risk and aggravation of atherosclerotic cardiovascular diseases. However, whether intestinal microbiota is implicated in the mechanisms linking CIH to arteriosclerosis (AS) pathogenesis remains unclear. The association of CIH with the development of altered gut microbiota (GM) may provide the opportunity to develop preventive strategies for atherosclerotic cardiovascular risk reduction. Animal models of apolipoprotein E-deficient (apoE) mice treated with high-fat diet (HFD) and subjected to CIH conditions was applied to mimic the AS observed in patients with OSA. The physiological status and atherosclerotic lesion formation were confirmed by histological analysis. 16S rDNA sequencing of fecal samples was conducted to determine the changes in gut microbial composition. Morphometric analysis demonstrated that CIH caused aggravated atherosclerotic lesions and facilitated AS in apoE mice treated with HFD. The gut bacteria was significantly varied in AS and AS+CIH mice compared with that in the control mice. Significantly perturbed GM profiles were detected in AS mice with and without CIH, with altered microbial α- and β- diversity and shifts in bacterial compositions at phylum and genus levels. While the difference between AS and AS+CIH was observed at different bacteria taxa levels. Aggravation of reduced and increased , and Oceanospirillales was noted in CIH-treated AS mice. The correlation of intestinal bacterial parameters with pathological changes in artery indicated complicated interactions under CIH-induced GM dysbiosis. Furthermore, the gut microbial functions in the potential ability of replication recombination and repair proteins, glycan biosynthesis and metabolism, as well as metabolism of cofactors and vitamins were identified to be further suppressed by CIH. Our findings demonstrated a causal effect of CIH on GM alterations in AS mice and suggested that the disordered GM features in AS development were deteriorated by CIH, which may be associated with AS aggravation. Preventative strategies targeting gut microbiome are highly recommended for intervention of OSA-related AS.
慢性间歇性低氧（CIH）是普遍存在的阻塞性睡眠呼吸暂停（OSA）病理生理学的显著特征，这导致动脉粥样硬化性心血管疾病风险增加和恶化。然而，肠道微生物群是否参与 CIH 与动脉粥样硬化（AS）发病机制的联系尚不清楚。CIH 与肠道微生物群（GM）改变的关联可能为降低动脉粥样硬化性心血管风险的预防策略提供机会。应用载脂蛋白 E 缺陷（apoE）小鼠高脂饮食（HFD）和 CIH 条件处理的动物模型来模拟 OSA 患者观察到的 AS。通过组织学分析证实生理状态和动脉粥样硬化病变形成。对粪便样本进行 16S rDNA 测序以确定肠道微生物组成的变化。形态计量分析表明，CIH 导致喂食 HFD 的 apoE 小鼠的动脉粥样硬化病变加重并促进 AS。与对照小鼠相比，AS 和 AS+CIH 小鼠的肠道细菌明显不同。在有和没有 CIH 的 AS 小鼠中检测到明显扰动的 GM 谱，微生物 α-和 β-多样性发生改变，门和属水平的细菌组成发生变化。而在 AS 和 AS+CIH 之间的差异则在不同的细菌分类群水平上观察到。在 CIH 治疗的 AS 小鼠中观察到减少和增加的和 Oceanospirillales 的加剧。肠道细菌参数与动脉病理变化的相关性表明，在 CIH 诱导的 GM 失调下存在复杂的相互作用。此外，还确定了肠道微生物功能在复制重组和修复蛋白、聚糖生物合成和代谢以及辅因子和维生素代谢方面的潜在能力进一步受到 CIH 的抑制。我们的研究结果表明 CIH 对 AS 小鼠 GM 改变有因果关系，并表明 CIH 加剧了 AS 发展中紊乱的 GM 特征，这可能与 AS 加重有关。建议针对肠道微生物组的预防策略作为 OSA 相关 AS 的干预措施。
