Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of
cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As
lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study,
ApoE-/- mice fed with a high-fat diet (HFD) were subjected to
ovariectomy and supplemented with
estrogen. The ovariectomized HFD-fed
ApoE-/- mice underwent significant AS damage, hepatic
lipid damage,
hyperlipidemia, and changes of lipid metabolism- and transport-related
enzymes. There was significantly higher abundance of some
lipid metabolites in the plasma of ovariectomized HFD-fed
ApoE-/- mice than in non-ovariectomized ones, including
cholesterol esters,
triglycerides,
phospholipids, and other types of
lipids (
free fatty acids,
acylcarnitine,
sphingomyelins, and
ceramides). The administration of
estrogen significantly reduced the contents of most
lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed
ApoE-/- mice, compared to HFD-fed
ApoE-/- mice without
ovariectomy. In contrast, with
estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed
ApoE-/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the
transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed
ApoE-/- mice was sufficient to correct the
hyperlipidemia and AS damage, and to reverse the characteristics changing of
lipid metabolomics in ovariectomized HFD-fed
ApoE-/- mice. These phenomena were also been observed after
transplantation of feces from
estrogen-treated ovariectomized HFD-fed
ApoE-/- mice to ovariectomized HFD-fed
ApoE-/- mice. Moreover, the gut microbiota and
lipid metabolites were significantly correlated, demonstrating that the changes of serum
lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating
lipid metabolites.
Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.