AUTHOR=Yang Mei , Shi Fang-Hong , Liu Wen , Zhang Min-Chun , Feng Ri-Lu , Qian Cheng , Liu Wei , Ma Jing 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00635

DOI=10.3389/fendo.2020.00635

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> Four-week-old male Sprague Dawley rats (<italic>n</italic> = 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 (<italic>n</italic> = 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.</p><p><bold>Results:</bold> Dapagliflozin significantly decreased fasting and postprandial blood glucose levels as metformin in type 2 diabetic rats (<italic>P</italic> &lt; 0.001). Enterotype was composed of <italic>Ruminococcaceae</italic> after treatment of dapagliflozin, whereas <italic>Ruminococcaceae</italic> and <italic>Muribaculaceae</italic> were the main enterotypes following metformin treatment. Dapagliflozin did not increase the abundance of beneficial bacteria including <italic>Lactobacillaceae</italic> and <italic>Bifidobacteriaceae</italic>. However, these were increased in the metformin group. It is surprising to find that <italic>Proteobacteria</italic> (especially <italic>Desulfovibrionaceae</italic>) were enriched in the dapagliflozin group.</p><p><bold>Conclusion:</bold> 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.</p>