Empagliflozin improves gut microbial disturbances and intestinal barrier integrity in STZ-induced type 2 diabetic mice
Abstract
Intestinal barrier dysfunction and gut microbiota dysbiosis contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). However, the effects of empagliflozin on the gut microbiota-intestinal barrier axis remain incompletely understood. This study investigated whether empagliflozin improves intestinal barrier integrity and gut microbiota profiles in a streptozotocin (STZ)-induced murine model of T2DM. Male C57BL/6 mice were fed a high-fat diet followed by STZ injection to induce T2DM and then treated with empagliflozin (10 mg/kg/day) for 8 weeks. Intestinal barrier-related proteins were assessed by immunofluorescence and western blotting. Gut microbial profiles were analyzed using 16S rRNA gene sequencing. Short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), and inflammatory cytokines were quantified by GC-MS and ELISA. Empagliflozin treatment significantly reduced fasting blood glucose levels and attenuated weight gain in diabetic mice. Diabetic animals exhibited compromised intestinal barrier structure, accompanied by decreased tight junction protein expression (Claudin-1 and ZO-1) and enhanced TLR4/MyD88/NF-κB signaling, which were substantially alleviated following empagliflozin treatment. Concurrently, elevated inflammatory cytokines (IL-1β, IL-6, and TNF-α) and LPS levels were significantly reduced following empagliflozin treatment. Microbiome analyses revealed treatment-associated reorganization of gut microbial communities, including altered β-diversity…
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