Targeting the Gut–Heart Axis in Diabetic Heart Failure: Microbiota and SGLT2is as Converging Therapeutic Frontiers

Emerging evidence highlights the gut microbiota as a critical modulator in the pathogenesis of heart failure (HF), particularly among patients with type 2 diabetes mellitus (T2DM). Dysbiosis contributes to systemic inflammation, endothelial dysfunction, and adverse cardiac remodeling via microbial metabolites such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs). However, the therapeutic intersection between the gut microbiota and pharmacological interventions remains insufficiently integrated. Sodium-glucose cotransporter-2 inhibitors (SGLT2is), a cornerstone of T2DM management, confer cardioprotective effects that may involve microbiota-mediated pathways. This review provides a novel synthesis of how SGLT2is influence gut ecology, specifically through altered glucose excretion and osmotic shifts, to potentially restore SCFA-producing taxa. By delineating the structural transitions from gut physiology to SGLT2i-modulated cardiac outcomes, we emphasize the gut-heart axis as a pivotal therapeutic target. This focused framework offers new insights into the triadic interplay between microbiome stability and cardiometabolic health, moving beyond traditional glucose-centric paradigms.