Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis

Naofumi Yoshida; Takuo Emoto; Tomoya Yamashita; Hikaru Watanabe; Tomohiro Hayashi; Tokiko Tabata; Namiko Hoshi; Naoya Hatano; Genki Ozawa; Naoto Sasaki; Taiji Mizoguchi; Hilman Zulkifli Amin; Yushi Hirota; Wataru Ogawa; Takuji Yamada; Ken Ichi Hirata

doi:10.1161/CIRCULATIONAHA.118.033714

Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis

Naofumi Yoshida, Takuo Emoto, Tomoya Yamashita, Hikaru Watanabe, Tomohiro Hayashi, Tokiko Tabata, Namiko Hoshi, Naoya Hatano, Genki Ozawa, Naoto Sasaki, Taiji Mizoguchi, Hilman Zulkifli Amin, Yushi Hirota, Wataru Ogawa, Takuji Yamada, Ken Ichi Hirata

Research output: Contribution to journal › Article › peer-review

309 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2486-2498
Number of pages	13
Journal	Circulation
Volume	138
Issue number	22
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.118.033714
Publication status	Published - Nov 27 2018
Externally published	Yes

Keywords

Bacteroides dorei
Bacteroides vulgatus
coronary artery disease
gut microbiome
lipopolysaccharide

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/CIRCULATIONAHA.118.033714

Cite this

Yoshida, N., Emoto, T., Yamashita, T., Watanabe, H., Hayashi, T., Tabata, T., Hoshi, N., Hatano, N., Ozawa, G., Sasaki, N., Mizoguchi, T., Amin, H. Z., Hirota, Y., Ogawa, W., Yamada, T., & Hirata, K. I. (2018). Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis. Circulation, 138(22), 2486-2498. https://doi.org/10.1161/CIRCULATIONAHA.118.033714

Yoshida, N, Emoto, T, Yamashita, T, Watanabe, H, Hayashi, T, Tabata, T, Hoshi, N, Hatano, N, Ozawa, G, Sasaki, N, Mizoguchi, T, Amin, HZ, Hirota, Y, Ogawa, W, Yamada, T & Hirata, KI 2018, 'Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis', Circulation, vol. 138, no. 22, pp. 2486-2498. https://doi.org/10.1161/CIRCULATIONAHA.118.033714

@article{6c2d85394fd24c928346a5a09f49fbac,

title = "Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis",

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.",

keywords = "Bacteroides dorei, Bacteroides vulgatus, coronary artery disease, gut microbiome, lipopolysaccharide",

author = "Naofumi Yoshida and Takuo Emoto and Tomoya Yamashita and Hikaru Watanabe and Tomohiro Hayashi and Tokiko Tabata and Namiko Hoshi and Naoya Hatano and Genki Ozawa and Naoto Sasaki and Taiji Mizoguchi and Amin, {Hilman Zulkifli} and Yushi Hirota and Wataru Ogawa and Takuji Yamada and Hirata, {Ken Ichi}",

note = "Funding Information: This work was supported by Japan Society for the Promotion of Science KAK-ENHI grant Nos. 24591114 (T.Y.), 16K09516 (T.Y.), and 17K09497 (K.H.), the Japanese Circulation Society Translational Research Foundation (K.H.), the Ue-hara Memorial Foundation (K.H.), the Suzuken Memorial Foundation (N.S.), the Takeda Scientific Foundation (N.S. and T.Y.), the Senshin Medical Research Foundation (T.Y.), the Yakult Bioscience Research Foundation (T.Y.), the Hyogo Science and Technology Association (T.Y. and K.H.), the Mishima Kaiun Memorial Foundation (T.E.), and the Kondou Kinen Medical Foundation (T.Y.). Funding Information: This work was supported by Japan Society for the Promotion of Science KAKENHI grant Nos. 24591114 (T.Y.), 16K09516 (T.Y.), and 17K09497 (K.H.), the Japanese Circulation Society Translational Research Foundation (K.H.), the Uehara Memorial Foundation (K.H.), the Suzuken Memorial Foundation (N.S.), the Takeda Scientific Foundation (N.S. and T.Y.), the Senshin Medical Research Foundation (T.Y.), the Yakult Bioscience Research Foundation (T.Y.), the Hyogo Science and Technology Association (T.Y. and K.H.), the Mishima Kaiun Memorial Foundation (T.E.), and the Kondou Kinen Medical Foundation (T.Y.). Publisher Copyright: {\textcopyright} 2018 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.",

year = "2018",

month = nov,

day = "27",

doi = "10.1161/CIRCULATIONAHA.118.033714",

language = "English",

volume = "138",

pages = "2486--2498",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "22",

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TY - JOUR

T1 - Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis

AU - Yoshida, Naofumi

AU - Emoto, Takuo

AU - Yamashita, Tomoya

AU - Watanabe, Hikaru

AU - Hayashi, Tomohiro

AU - Tabata, Tokiko

AU - Hoshi, Namiko

AU - Hatano, Naoya

AU - Ozawa, Genki

AU - Sasaki, Naoto

AU - Mizoguchi, Taiji

AU - Amin, Hilman Zulkifli

AU - Hirota, Yushi

AU - Ogawa, Wataru

AU - Yamada, Takuji

AU - Hirata, Ken Ichi

N1 - Funding Information: This work was supported by Japan Society for the Promotion of Science KAK-ENHI grant Nos. 24591114 (T.Y.), 16K09516 (T.Y.), and 17K09497 (K.H.), the Japanese Circulation Society Translational Research Foundation (K.H.), the Ue-hara Memorial Foundation (K.H.), the Suzuken Memorial Foundation (N.S.), the Takeda Scientific Foundation (N.S. and T.Y.), the Senshin Medical Research Foundation (T.Y.), the Yakult Bioscience Research Foundation (T.Y.), the Hyogo Science and Technology Association (T.Y. and K.H.), the Mishima Kaiun Memorial Foundation (T.E.), and the Kondou Kinen Medical Foundation (T.Y.). Funding Information: This work was supported by Japan Society for the Promotion of Science KAKENHI grant Nos. 24591114 (T.Y.), 16K09516 (T.Y.), and 17K09497 (K.H.), the Japanese Circulation Society Translational Research Foundation (K.H.), the Uehara Memorial Foundation (K.H.), the Suzuken Memorial Foundation (N.S.), the Takeda Scientific Foundation (N.S. and T.Y.), the Senshin Medical Research Foundation (T.Y.), the Yakult Bioscience Research Foundation (T.Y.), the Hyogo Science and Technology Association (T.Y. and K.H.), the Mishima Kaiun Memorial Foundation (T.E.), and the Kondou Kinen Medical Foundation (T.Y.). Publisher Copyright: © 2018 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

PY - 2018/11/27

Y1 - 2018/11/27

N2 - 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.

AB - 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.

KW - Bacteroides dorei

KW - Bacteroides vulgatus

KW - coronary artery disease

KW - gut microbiome

KW - lipopolysaccharide

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AN - SCOPUS:85058923055

SN - 0009-7322

VL - 138

SP - 2486

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JO - Circulation

JF - Circulation

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ER -

Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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