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

29 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

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

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, K. I. (2017). Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. Journal of Lipid Research, 58(3), 519-528. https://doi.org/10.1194/jlr.M072165