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

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

  • Cell Host Microbe. 2022 Oct 12;30(10):1450-1463.e8. doi: 10.1016/j.chom.2022.09.004.
Zhenyu Tian 1,  Yun Zhang 1,  Zhijian Zheng 1,  Meng Zhang 1,  Tao Zhang 2,  Jiajia Jin 1,  Xinjie Zhang 3,  Guixiang Yao 1,  Danxia Kong 4,  Cheng Zhang 5,  Zhe Wang 6,  Qunye Zhang 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250036, China.
  • 3 Department of Biology, University College London, London NW1 2HE, UK.
  • 4 Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan 250026, China.
  • 5 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. Electronic address: zhangc@sdu.edu.cn.
  • 6 Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan 250026, China. Electronic address: wangzhe.zqy@email.sdu.edu.cn.
  • 7 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; Cardiovascular Disease Research Center of Shandong First Medical University, Central Hospital Affiliated to Shandong First Medical University, Jinan 250028, China. Electronic address: wz.zhangqy@sdu.edu.cn.
PMID: 36228585 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.

Keywords

AAA; NET; Roseburia intestinalis; abdominal aortic aneurysm; butyrate; gut microbiome; neutrophil extracellular trap.

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