Hao Han, Li Zhu, Qiao Shi-Yang, Qi Yu, Xu Xiao-Ying, Si Jia-Yi, Liu Yi-Hai, Chang Lei, Shi Yi-Fan, Xu Biao, Wei Zhong-Hai, Kang Li-Na
Department of Cardiology, Affiliated Drum Tower Hospital, Medical School, Nanjing University, No.321, Zhongshan Road, Nanjing, 210008, China.
Department of Cardiology, Nanjing Drum Hospital, Clinical College of Nanjing University of Chinese Medicine, No.138, Xian-Lin Avenue, Nanjing, 210008, China.
Atherosclerosis. 2023 Apr;371:32-40. doi: 10.1016/j.atherosclerosis.2023.03.011. Epub 2023 Mar 20.
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora.
Six-week-old male ApoE mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n = 9) or saline (Ctrl group, n = 6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n = 6) or from Ctrl (FMT-Ctrl group, n = 6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses.
In comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p < 0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group.
Empagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.
据报道，钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）可减轻动脉粥样硬化。此外，有研究表明肠道菌群会影响动脉粥样硬化的进展。在此，我们旨在研究SGLT2i是否能通过肠道菌群减轻动脉粥样硬化。
给6周龄高脂饮食喂养的雄性ApoE小鼠灌胃恩格列净（SGLT2i组，n = 9）或生理盐水（对照组，n = 6），持续12周。实验结束时收集两组小鼠的粪便进行粪便微生物群移植（FMT）。另外12只6周龄高脂饮食喂养的雄性ApoE小鼠接受来自SGLT2i组（FMT-SGLT2i组，n = 6）或对照组（FMT-Ctrl组，n = 6）粪便的FMT。收集血液、组织和粪便样本用于后续分析。
与对照组相比，SGLT2i组的动脉粥样硬化程度较轻（p < 0.0001），粪便中益生菌如柯里杆菌科、S24-7、毛螺菌科和阿德勒克雷茨菌属的丰度更高。此外，恩格列净可显著降低炎症反应并改变肠道菌群代谢。有趣的是，与FMT-Ctrl组相比，FMT-SGLT2i组的动脉粥样硬化和全身炎症反应也有所减轻，肠道菌群组成和相关代谢产物的变化与SGLT2i组相似。
恩格列净似乎部分通过调节肠道微生物群减轻动脉粥样硬化，且这种抗动脉粥样硬化作用可通过肠道菌群移植传递。
