Journal Article 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

58 ( 3 )  , pp.519 - 528 , 2017-03 , American Society for Biochemistry and Molecular Biology
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 (GF) or conventionally raised (Conv) Apolipoprotein E deficient (ApoE(-/-)) mice were fed chow diet and sacrificed at twenty weeks of age. We found lack of gut microbiota in ApoE(-/-) mice caused a significant increase in the plasma and hepatic cholesterol levels compared to ConvR ApoE(-/-) mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the entero-hepatic fibroblast growth factor 15 (FGF15) - fibroblast growth factor receptor 4 (FGFR4) axis, and reduction of cholesterol 7α-hydroxylase (CYP7A1) 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 to 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.

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