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

研究成果: Article査読

49 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)519-528
ページ数10
ジャーナルJournal of lipid research
58
3
DOI
出版ステータスPublished - 2017 3 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 内分泌学
  • 細胞生物学

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