Dapagliflozin modulates the faecal microbiota after myocardial infarction in non‐diabetic mice

Abstract

The gut microbiota seems to be a major modulator of cardiovascular diseases, such as myocardial infarction. Dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2i), is an antidiabetic agent that was recently utilized in patients with cardiovascular diseases. This study aims to investigate the effects of dapagliflozin on the faecal microbiota of postinfarction non‐diabetic mice. A total of 19 male mice were randomly divided into three groups, where two groups were enduced with myocardial infarction (MI) by left anterior descending ligation. One day after the surgery, each group was administered normal saline (15 mL/kg/day, 0.9%) or dapagliflozin (1.5 mg/kg/day) for 4 weeks. Echocardiography was obtained on day 28 post MI. Masson's trichrome staining was used to determine the degree of fibrosis. Faecal samples were collected to assess the microbiome by 16S ribosomal RNA gene sequencing. We found that dapagliflozin significantly improved cardiac function in the non‐diabetic myocardial infarction mice model after the 28‐day treatment, especially in ejection fraction and fractional shortening (p < 0.01). Enterotypes were composed of Muribaculaceae and Lactobacillaceae after dapagliflozin treatment, while Muribaculaceae and Erysipelotrichaceae were the main enterotypes post‐MI. Dapagliflozin increased the abundance of beneficial bacteria like Lactobacillaceae, while decreasing the abundance of beneficial bacteria like Bifidobacteriaceae. It was interesting to discover that Proteobacteria (especially Desulfovibrionaceae) were enriched after the dapagliflozin treatment for myocardial infarction. Dapagliflozin increased the abundance of the main beneficial bacteria. In post‐myocardial infarction treatments, using dapagliflozin could positively contribute to the improvement of cardiac function and alter the structure of faecal microbiota.

Dapagliflozin-affected endothelial dysfunction and altered gut microbiota in mice with heart failure

“…Our findings demonstrated dapagliflozin could improve endothelial dysfunction in mice undergoing HF via targeting gut microbiota, thereby contributing to the recovery of myocardial function. It is the difference between our findings and the report by Li et al (2023) . The functional prediction of altered microbiota indicated these microbiotas ameliorated endothelial dysfunction in mice with HF by modulating the biosynthesis and degradation of metabolites.…”

“…Recent study by Li et al (2023) showed the role of dapagliflozin in gut microbiota based on a model of LDA ligation. They found dapagliflozin modulated gut microbiota to improve myocardial dysfunction.…”

Gut Microbiota and Cardiovascular Disease: Evidence on the Metabolic and Inflammatory Background of a Complex Relationship

“…In a recent study, empagliflozin was able to promote a selection of SCFAs-producing bacteria, such as Roseburia, Faecalibacterium, and Eubacterium over potentially harmful bacteria, including Escherichia-Shigella, Bilophila, and Hungatella [147]. In another study, a 28-day treatment with dapagliflozin, another SGLT2i, significantly improved cardiac function in the non-diabetic myocardial infarction mice model and modified the gut microbiota composition, increasing the abundance of beneficial bacteria such as Lactobacillaceae [148]. Muribaculaceae and Lactobacillaceae were the main components of the intestinal microbial community after treatment with dapagliflozin, while Muribaculaceae and Erysipelotrichaceae were the ones associated with myocardial infarction.…”

From multi-omics approaches to personalized medicine in myocardial infarction

“…This provides direction for the development of new biologics or dietary interventions. Secondely, studies have shown that gut microbiota remodeling through certain interventions, such as Lactobacillus johnsonii, dapagliflozin, and flavonoids, can result in enhanced cardiac function after AMI (253)(254)(255). SCFAs have been found to improve cardiomyocyte function and heart contractility (244,256).…”