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Dapagliflozin enhances gut barrier function in rats with chronic myocardial infarction by modulating gut microbiota
Chanon Kunasol1,2, Chayodom Maneechote1,2, Nattayaporn Apaijai1,2,3
1Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Background:
Chronic myocardial infarction (CMI) is a leading cause of heart failure and is increasingly recognized as a systemic condition involving multi-organ dysfunction, particularly impaired gut health due to systemic inflammation and metabolic disturbances. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, exerts cardioprotective effects beyond glycemic control, but its role in CMI-induced gut dysbiosis and barrier dysfunction remains unclear. This study aimed to determine whether dapagliflozin mitigates CMI-induced gut dysbiosis and intestinal barrier dysfunction-alongside systemic inflammation and metabolic disturbances-and whether these changes are associated with improved cardiac function.
Methods:
Thirty-nine male Wistar rats underwent left anterior descending (LAD) coronary artery ligation (CMI, n=26) or sham surgery (n=13). One-week post-surgery, CMI rats with anterior wall akinesia and left ventricular ejection fraction (LVEF) <50% were randomized to receive vehicle (distilled water; n=13) or dapagliflozin (1 mg/kg/day, oral; n=13) for 10 weeks. Outcomes measured included cardiac function, gut microbiota composition, gut barrier integrity, intestinal apoptosis, inflammatory cytokines, and levels of plasma microbial metabolites-short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO).
Results:
Dapagliflozin improved cardiac function and attenuated CMI-induced gut dysbiosis by restoring microbial diversity, enriching beneficial bacteria (UCG-007, Bacillus), and reducing harmful taxa (Holdemania). Gut barrier integrity was preserved through upregulation of tight junction proteins (TJPs) and suppression of intestinal apoptosis and inflammation. Metabolically, dapagliflozin increased butyrate production while lowering plasma TMAO levels, indicating a favorable microbial metabolic shift.
Conclusions:
In this CMI rat model, dapagliflozin was associated with changes in the gut-heart axis that may relate to its observed cardioprotective effects. Further studies are required to determine causality and the relative contribution of these pathways.
