Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis

Kazuyuki Kasahara, Takeshi Tanoue, Tomoya Yamashita, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Taiji Mizoguchi, Tomohiro Hayashi, Naoki Kitano, Naoto Sasaki, Koji Atarashi, Kenya Honda, Ken Ichi Hirata

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE-/-) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE-/- mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE-/- mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE-/- mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.

Original languageEnglish
Pages (from-to)519-528
Number of pages10
JournalJournal of Lipid Research
Volume58
Issue number3
DOIs
Publication statusPublished - 2017 Mar 1
Externally publishedYes

Fingerprint

Apolipoproteins E
Atherosclerosis
Bacteria
Homeostasis
Cholesterol
Inflammation
Bile Acids and Salts
Receptor, Fibroblast Growth Factor, Type 4
Cholesterol 7-alpha-Hydroxylase
Liver
Fibroblast Growth Factors
Nutrition
Microbiota
Lipopolysaccharides
Hypercholesterolemia
Ileum
Lipid Metabolism
Chemical activation
Plasmas
Gastrointestinal Microbiome

Keywords

  • bile acid metabolism
  • cholesterol/metabolism
  • gut microbiota
  • macrophages
  • nuclear receptors/farnesoid X receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. / Kasahara, Kazuyuki; Tanoue, Takeshi; Yamashita, Tomoya; Yodoi, Keiko; Matsumoto, Takuya; Emoto, Takuo; Mizoguchi, Taiji; Hayashi, Tomohiro; Kitano, Naoki; Sasaki, Naoto; Atarashi, Koji; Honda, Kenya; Hirata, Ken Ichi.

In: Journal of Lipid Research, Vol. 58, No. 3, 01.03.2017, p. 519-528.

Research output: Contribution to journalArticle

Kasahara, K, Tanoue, T, Yamashita, T, Yodoi, K, Matsumoto, T, Emoto, T, Mizoguchi, T, Hayashi, T, Kitano, N, Sasaki, N, Atarashi, K, Honda, K & Hirata, KI 2017, 'Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis', Journal of Lipid Research, vol. 58, no. 3, pp. 519-528. https://doi.org/10.1194/jlr.M072165
Kasahara, Kazuyuki ; Tanoue, Takeshi ; Yamashita, Tomoya ; Yodoi, Keiko ; Matsumoto, Takuya ; Emoto, Takuo ; Mizoguchi, Taiji ; Hayashi, Tomohiro ; Kitano, Naoki ; Sasaki, Naoto ; Atarashi, Koji ; Honda, Kenya ; Hirata, Ken Ichi. / Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. In: Journal of Lipid Research. 2017 ; Vol. 58, No. 3. pp. 519-528.
@article{11cb9d202431448e9d89026339ee3a17,
title = "Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis",
abstract = "The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE-/-) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE-/- mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE-/- mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE-/- mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.",
keywords = "bile acid metabolism, cholesterol/metabolism, gut microbiota, macrophages, nuclear receptors/farnesoid X receptor",
author = "Kazuyuki Kasahara and Takeshi Tanoue and Tomoya Yamashita and Keiko Yodoi and Takuya Matsumoto and Takuo Emoto and Taiji Mizoguchi and Tomohiro Hayashi and Naoki Kitano and Naoto Sasaki and Koji Atarashi and Kenya Honda and Hirata, {Ken Ichi}",
year = "2017",
month = "3",
day = "1",
doi = "10.1194/jlr.M072165",
language = "English",
volume = "58",
pages = "519--528",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis

AU - Kasahara, Kazuyuki

AU - Tanoue, Takeshi

AU - Yamashita, Tomoya

AU - Yodoi, Keiko

AU - Matsumoto, Takuya

AU - Emoto, Takuo

AU - Mizoguchi, Taiji

AU - Hayashi, Tomohiro

AU - Kitano, Naoki

AU - Sasaki, Naoto

AU - Atarashi, Koji

AU - Honda, Kenya

AU - Hirata, Ken Ichi

PY - 2017/3/1

Y1 - 2017/3/1

N2 - The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE-/-) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE-/- mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE-/- mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE-/- mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.

AB - The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE-/-) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE-/- mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE-/- mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE-/- mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.

KW - bile acid metabolism

KW - cholesterol/metabolism

KW - gut microbiota

KW - macrophages

KW - nuclear receptors/farnesoid X receptor

UR - http://www.scopus.com/inward/record.url?scp=85021899083&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021899083&partnerID=8YFLogxK

U2 - 10.1194/jlr.M072165

DO - 10.1194/jlr.M072165

M3 - Article

C2 - 28130274

AN - SCOPUS:85021899083

VL - 58

SP - 519

EP - 528

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 3

ER -