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

Zhongming Li1, Kai Wang2, Yinzhang Ding2

  • 1Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Insights

Dapagliflozin improved cardiac function in mice after myocardial infarction by altering gut microbiota composition. The treatment increased beneficial bacteria and positively impacted heart health.

Area of Science:

  • Cardiovascular Research
  • Microbiome Research
  • Pharmacology

Background:

  • The gut microbiota plays a crucial role in cardiovascular disease development, including myocardial infarction.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i), like dapagliflozin, are used for diabetes and show potential in cardiovascular conditions.

Purpose of the Study:

  • To investigate the impact of dapagliflozin on the fecal microbiota of non-diabetic mice following myocardial infarction.
  • To assess the therapeutic effects of dapagliflozin on cardiac function and gut microbiome structure post-myocardial infarction.

Main Methods:

  • Myocardial infarction was induced in male mice, followed by administration of saline or dapagliflozin for 4 weeks.
  • Cardiac function was evaluated using echocardiography, and cardiac fibrosis was assessed via Masson's trichrome staining.
  • Fecal samples were analyzed using 16S ribosomal RNA gene sequencing to determine microbial composition and changes.

Main Results:

  • Dapagliflozin significantly improved cardiac function, notably ejection fraction and fractional shortening, in myocardial infarction mice (p < 0.01).
  • Microbiome analysis revealed shifts in enterotypes, with an increase in beneficial bacteria like Lactobacillaceae and enrichment of Proteobacteria (Desulfovibrionaceae).
  • Dapagliflozin treatment altered the gut microbiota structure, increasing beneficial bacteria abundance compared to the post-myocardial infarction state.

Conclusions:

  • Dapagliflozin demonstrates a positive effect on cardiac function in a non-diabetic myocardial infarction mouse model.
  • The therapeutic benefits of dapagliflozin are associated with significant alterations in the gut microbiota structure.
  • Dapagliflozin holds potential as a post-myocardial infarction treatment, influencing both cardiac health and the gut microbiome.