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 inApoE-/-mice caused a significant increase in the plasma and hepatic cholesterol levels compared with ConvApoE-/-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 ConvApoE-/-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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.|Department of Bacteriology, University of Wisconsin-Madison, Madison, WI.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kasahara
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanoue
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan tomoya@med.kobe-u.ac.jp.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yodoi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Emoto
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Mizoguchi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitano
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Atarashi
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D004032:Diet; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000235:genetics; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C108526:fibroblast growth factor 15, mouse; D005346:Fibroblast Growth Factors; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D051499:Receptor, Fibroblast Growth Factor, Type 4
keywords: bile acid metabolism; cholesterol/metabolism; gut microbiota; macrophages; nuclear receptors/farnesoid X receptor