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肠道微生物组失调通过促进中性粒细胞胞外诱捕网形成导致腹主动脉瘤。

Gut microbiome dysbiosis contributes to abdominal aortic aneurysm by promoting neutrophil extracellular trap formation.

机构信息

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.

Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250036, China.

出版信息

Cell Host Microbe. 2022 Oct 12;30(10):1450-1463.e8. doi: 10.1016/j.chom.2022.09.004.

Abstract

Abdominal aortic aneurysm (AAA) is an insidious and lethal vascular disease that lacks effective nonsurgical interventions. Gut microbiota dysbiosis plays key roles in many diseases, but its relationship with AAA has not been fully elucidated. Herein, we reveal significant abnormalities in the gut microbe composition of AAA patients and confirm that gut microbiota dysbiosis is an important cause of AAA. Specifically, R. intestinalis was significantly reduced in AAA patients. Using AAA mice, we show that R. intestinalis and its metabolite butyrate significantly reduce neutrophil infiltration and NOX2-dependent neutrophil extracellular trap formation, inflammation, and abnormal phenotypic switching of vascular smooth muscle cells in the aortic wall, thereby markedly alleviating AAA development. Our research uncovers the role and mechanism of the gut microbiota in AAA development and provides insights into AAA prophylaxis from a microecological perspective.

摘要

腹主动脉瘤(AAA)是一种隐匿且致命的血管疾病,缺乏有效的非手术干预措施。肠道微生物失调在许多疾病中起着关键作用,但它与 AAA 的关系尚未完全阐明。在此,我们揭示了 AAA 患者肠道微生物组成的显著异常,并证实了肠道微生物失调是 AAA 的一个重要原因。具体而言,AAA 患者的 R. intestinalis 显著减少。通过使用 AAA 小鼠,我们表明 R. intestinalis 和其代谢产物丁酸盐可显著减少中性粒细胞浸润和 NADPH 氧化酶 2 依赖性中性粒细胞胞外诱捕网的形成、炎症以及主动脉壁中血管平滑肌细胞的异常表型转换,从而显著缓解 AAA 的发展。我们的研究揭示了肠道微生物群在 AAA 发展中的作用和机制,并从微生态学角度为 AAA 的预防提供了新的见解。

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