Background:Exercise elicits cardiometabolic benefits,reducing the risks of cardiovascular diseases and type 2 diabetes.This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise...Background:Exercise elicits cardiometabolic benefits,reducing the risks of cardiovascular diseases and type 2 diabetes.This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism.Methods:Leptin receptor-deficient diabetic(db/db)and nondiabetic(db/m+)mice underwent running treadmill exercise for 8 weeks,during which fecal microbiota transplantation(FMT)was parallelly performed from exercise-trained to sedentary diabetic(db/db)mice.Endothelial function,glucose homeostasis,physical performance,and vascular signaling of recipient mice were assessed.Vascular and intestinal stresses,including inflammation,oxidative stress,and endoplasmic reticulum(ER)stress,were investigated.RNA sequencing analysis on mouse aortic and intestinal tissues was performed.Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing.Results:Chronic exercise improved vascular and metabolic abnormalities in donor mice.Likewise,FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice.Exercise-associated FMT enhanced endothelial function in different arteries,suppressed vascular and intestinal stresses,and improved glucose homeostasis in recipient mice,with noted microRNA181b upregulation in aortas and intestines.Altered gut microbiota profiles and gut-derived factors(e.g.,short-chain fatty acids and glucagon-like peptide-1)as well as improved intestinal integrity shall contribute to the cardiometabolic benefits,implying a gut‒vascular connection.Conclusion:This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice,extending the beneficial mechanism of exercise through gut‒vascular communication.The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.展开更多
基金funded by the Health and Medical Research Fund(Grant No.08190776)Hong Kong Research Grants Council(T12-101/23-N,SRFS2021-4S04 to Yu Huang,and T11-104/22-R to Sheng Chen)supported by a fellowship award from the Research Grants Council of the Hong Kong Special Administrative Region,China(Project No.CityU PDFS22231S01).
文摘Background:Exercise elicits cardiometabolic benefits,reducing the risks of cardiovascular diseases and type 2 diabetes.This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism.Methods:Leptin receptor-deficient diabetic(db/db)and nondiabetic(db/m+)mice underwent running treadmill exercise for 8 weeks,during which fecal microbiota transplantation(FMT)was parallelly performed from exercise-trained to sedentary diabetic(db/db)mice.Endothelial function,glucose homeostasis,physical performance,and vascular signaling of recipient mice were assessed.Vascular and intestinal stresses,including inflammation,oxidative stress,and endoplasmic reticulum(ER)stress,were investigated.RNA sequencing analysis on mouse aortic and intestinal tissues was performed.Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing.Results:Chronic exercise improved vascular and metabolic abnormalities in donor mice.Likewise,FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice.Exercise-associated FMT enhanced endothelial function in different arteries,suppressed vascular and intestinal stresses,and improved glucose homeostasis in recipient mice,with noted microRNA181b upregulation in aortas and intestines.Altered gut microbiota profiles and gut-derived factors(e.g.,short-chain fatty acids and glucagon-like peptide-1)as well as improved intestinal integrity shall contribute to the cardiometabolic benefits,implying a gut‒vascular connection.Conclusion:This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice,extending the beneficial mechanism of exercise through gut‒vascular communication.The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.
