Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet

J Atheroscler Thromb. 2010 Aug 31;17(8):796-804. doi: 10.5551/jat.3285. Epub 2010 Apr 2.


Aim: The aim of our work was to determine the influence of intestinal bacteria on the development of atherosclerotic lesions using apolipoprotein E (ApoE)-deficient knockout mice.

Methods: The experiments were performed on ApoE-/--deficient mouse strain C57BL/6, bred under germ-free (GF) conditions for two generations or under conventional conditions with defined microflora (CV). The mice were fed a standard low cholesterol diet or cholesterol-rich diet for 3-4 months. We studied the development of advanced lesions in the thoracic and abdominal aorta by histological, morphometric and immunohistological methods.

Results: Conventionally reared ApoE-/- mice (containing no pathogenic intestinal microbiota) and fed a standard low cholesterol diet in contrast to a high cholesterol diet did not develop atherosclerotic aortic plaques. In contrast, ApoE-/- mice reared under germfree conditions for 2 generations and fed a low cholesterol diet exhibited atherosclerotic plaques in the aorta. Characteristic lipid deposition with foam cells and macrophages was found in their arterial walls.

Conclusion: In contrast to the absence of atherosclerotic plaques in conventionally reared ApoE-deficient mice, germ-free ApoE-/- mice consuming the same low cholesterol standard diet developed atherosclerotic plaques in the aorta. Differences in atherosclerotic plaques between GF and CV ApoE-/- mice are not so apparent when mice are fed a high cholesterol diet. Our findings thus document the protective effect of microbiota (commensal bacteria) on atherosclerosis development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology*
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology*
  • Apolipoproteins E / physiology*
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control*
  • Blotting, Western
  • Cholesterol / blood
  • Cholesterol, Dietary / administration & dosage*
  • Disease Models, Animal
  • Female
  • Germ-Free Life
  • Intestinal Mucosa / microbiology
  • Male
  • Metagenome*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Apolipoproteins E
  • Cholesterol, Dietary
  • RNA, Messenger
  • Cholesterol