Dapagliflozin Modulates the Fecal Microbiota in a Type 2 Diabetic Rat Model

Abstract

<b>Background:</b> The gut microbiota is recognized as a major modulator of metabolic disorders such as type 2 diabetes. Dapagliflozin, sodium glucose cotransporter 2 inhibitors (SGLT2i), enhances renal glucose excretion, and lowers blood glucose levels. The study aimed to determine the effects of dapagliflozin on fecal microbiota in a type 2 diabetic rat model. <b>Methods:</b> Four-week-old male Sprague Dawley rats (<i>n</i> = 24) were fed a high-fat diet (HFD) for 8 weeks and then given a single dose of STZ injection (30 mg/kg, i.p). They were randomly divided into three groups (<i>n</i> = 8). Each group received intragastric infusion of normal saline (2 ml, 0.9%) or metformin (215.15 mg/kg/day) or dapagliflozin (1 mg/kg/day) for 4 weeks. Blood glucose levels and plasma insulin levels were detected during intragastric glucose tolerance. Fecal samples were collected to access microbiome by 16S ribosomal RNA gene sequencing. <b>Results:</b> Dapagliflozin significantly decreased fasting and postprandial blood glucose levels as metformin in type 2 diabetic rats (<i>P</i> < 0.001). Enterotype was composed of <i>Ruminococcaceae</i> after treatment of dapagliflozin, whereas <i>Ruminococcaceae</i> and <i>Muribaculaceae</i> were the main enterotypes following metformin treatment. Dapagliflozin did not increase the abundance of beneficial bacteria including <i>Lactobacillaceae</i> and <i>Bifidobacteriaceae</i>. However, these were increased in the metformin group. It is surprising to find that <i>Proteobacteria</i> (especially <i>Desulfovibrionaceae</i>) were enriched in the dapagliflozin group. <b>Conclusion:</b> Dapagliflozin and metformin exerted complementary effects on the main beneficial bacteria. A combination of these two drugs might be beneficial to improve the structure of fecal microbiota in the treatment of type 2 diabetes.