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【論文摘要】Harnessing Anti-obesity Gut Microbiota for Improved Cardiovascular Risk Management

Abstracts


Commensal homeostasis of gut microbiota has been linked to cardiovascular pathologies and the inflammatory component modulated by gut microbiota also contributes significantly to atherosclerosis and hypertension. Obesity, a major contributor for type 2 diabetes and an important cardiovascular risk factor, has been linked with gut microbiota dysbiosis. This highlights the potential of harnessing the gut microbiota as a novel therapeutic strategy for cardiovascular diseases. With a high-fat diet (HFD)-induced obesity mouse model, we found that Dual-Specificity Phosphatase 6 (Dusp6)-deficient mice had reduced body weight gain and alleviated metabolic disorders. Notably, we found that the gut/fecal microbiota in Dusp6-deficient mice was more resistant to high-fat-diet-induced dysbiosis compared with wild-type mice. We used a gnotobiotic mouse model to demonstrate that fecal microbiota derived from Dusp6 deficient mice significantly increased the energy expenditure and reduced the weight-gain of recipient wild-type mice on high-fat diet. Our transcriptomic analyses have shown that Dusp6 deficient mice have reversed the HFD-induced disruption on intestinal barrier functions and mucosal immunity contributing to intestinal microbiome homeostasis. Since DUSP6 has been recently reported to promote endothelial inflammation, the function of DUSP6 in the context of obesity and cardiovascular diseases is complicated. Our studies shed light on obesity/metabolic syndrome/cardiovascular diseases with novel therapeutic candidates/strategies such as DUSP6 pharmacological inhibitors and the development of microbiota therapeutics.

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