Abstract 333: Protective Role of Gut Microbiota Akkermansia municiphila Against Development of Atherosclerosis in Mice
Gut microbiota is involved in both onset and progression of obesity. Obesity is associated with several cardiovascular diseases, among which atherosclerosis is the leading cause of morbidity and mortality. However, the role of gut microbiota in obesity-related cardiovascular complication remains to be explored. We found that the fecal amount of Akkermansia municiphila (Akk), a beneficial bacterium, decreased in apolipoprotein E-deficient (apoE -/-) mice fed a Western diet. In this study, we investigated whether Akk may exert beneficial role against the development of atherosclerosis.
ApoE -/- mice were oral gavaged with either PBS or Akk daily along with feeding a Western diet for 8 weeks. Atherosclerotic lesions in these mice were analyzed by H&E staining and Oil Red O staining. Local and systemic expressions of inflammatory molecules including MCP-1, ICAM, VCAM, IL-1beta and TNF-alpha were evaluated.
Western diet substantially altered gut microbiota pattern in apoE -/- mice. However, treatment of Akk, without changing the gut microbiota composition, significantly reduced atherosclerotic lesion. Although decreased body weight and fat mass were observed in Akk treatment group, the changing levels were physiologically insignificant. Serum total cholesterol, triglyceride, HDL and LDL levels were not affected by Akk treatment. However, local expression levels of MCP-1, ICAM, VCAM and TNF-alpha along with macrophage infiltration at the lesions were diminished by Akk. Furthermore, Akk treatment ameliorated systemic inflammatory status by decreasing circulating MCP-1 and IL1-beta levels. It appeared that Akk treatment was able to decrease gut permeability by inducing the expression levels of tight junction proteins, ZO-1 and occludin. Akk-induced reduction of gut permeability led to elimination of bacterial products penetration and serum LPS level was decreased. We speculated that the protective effect of Akk against atherosclerosis was mediated by decreasing gut permeability and LPS level in circulation.
Collectively, our results demonstrated that Akk can decrease atherosclerotic lesions by ameliorating local and systemic inflammation. Probiotic Akkermansia municiphila may be a potential therapeutic target for atherosclerosis.
Author Disclosures: J. Li: None. C. Woo: None. A. Xu: None.
- © 2015 by American Heart Association, Inc.