Naofumi Yoshida1, Takuo Emoto1, Tomoya Yamashita1, Hikaru Watanabe2, Tomohiro Hayashi1, Tokiko Tabata1, Namiko Hoshi3, Naoya Hatano4, Genki Ozawa5, Naoto Sasaki1, Taiji Mizoguchi1, Hilman Zulkifli Amin1,6, Yushi Hirota7, Wataru Ogawa7, Takuji Yamada2, Ken-Ichi Hirata1. 1. Division of Cardiovascular Medicine (N.Y., T.E., T.Y., T.H., T.T., N.S., T.M., H.Z.A., K.H.), Kobe University Graduate School of Medicine, Japan. 2. School of Life Science and Technology, Tokyo Institute of Technology, Japan (H.W., T.Y.). 3. Division of Gastroenterology (N.H.), Kobe University Graduate School of Medicine, Japan. 4. Department of Internal Medicine; Integrated Center for Mass Spectrometry, Laboratory Medicine (N.H.), Kobe University Graduate School of Medicine, Japan. 5. TechnoSuruga Laboratory Co, Ltd, Shizuoka, Japan (G.O.). 6. Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta (H.Z.A.). 7. Division of Diabetes and Endocrinology (Y.H., W.O.), Kobe University Graduate School of Medicine, Japan.
Abstract
BACKGROUND: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. METHODS: We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. RESULTS: Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei. CONCLUSIONS: Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. CLINICAL TRIAL REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.
BACKGROUND: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. METHODS: We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. RESULTS:Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei. CONCLUSIONS: Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. CLINICAL TRIAL REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.
Authors: Na Young Lee; Sang Jun Yoon; Dae Hee Han; Haripriya Gupta; Gi Soo Youn; Min Jea Shin; Young Lim Ham; Min Jung Kwak; Byung Yong Kim; Jeong Seok Yu; Do Yup Lee; Tae-Sik Park; Si-Hyun Park; Byoung Kook Kim; Hyun Chae Joung; In Suk Choi; Ji Taek Hong; Dong Joon Kim; Sang Hak Han; Ki Tae Suk Journal: Gut Microbes Date: 2020-01-22