Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites

• Published in: Nutrition & diabetes Vol. 14; no. 1; pp. 10 - 13
• Main Authors: Zhu, Jinxiu, Bao, Zhijun, Hu, Zuoqi, Wu, Shenglin, Tian, Cuihong, Zhou, Yueran, Ding, Zipeng, Tan, Xuerui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12-03-2024; Nature Publishing Group
• Subjects: 13/1; 13/51; 14/28; 38/1; 64/60; 692/163/2743/137/138; 692/699/75; 82/1; 82/51; Animals; Cardiac function; Cardiomyocytes; Cardiomyopathy; Clinical Nutrition; Diabetes; Diabetes Mellitus; Diabetic Cardiomyopathies; Diet, High-Fat; Epidemiology; Flavonoids; Gastrointestinal Microbiome; Hypertrophy; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Microbiota; Occludin - pharmacology
• ISSN: 2044-4052; 2044-4052
• DOI: 10.1038/s41387-024-00268-4

Background
The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota.
Methods
DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed.
Results
Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased.
Conclusions
Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function.