Effects of empagliflozin on gut microbiota in mice with type 2 diabetes mellitus-related diabetic nephropathy revealed by 16S rRNA sequencing

Background: The dysregulation of gut microbiota can be found in patients with type 2 diabetes mellitus (T2DM)-related diabetic nephropathy (DN). As a therapeutic medication of DN, inhibitors of sodium-glucose co-transporter 2 (SGLT2) were reported to affect the gut microbiota. This study aimed to identify whether empagliflozin (EMPA), an SGLT2 inhibitor, attenuated DN via regulating gut microbiota.Materials and Methods: The high-fat diet (HFD) combining streptozocin (STZ) injection was performed to induce DN in male C57BL/6J mice. Blood glucose was determined using the oral glucose tolerance test (OGTT). The therapeutic effects of intragastric administration of EMPA were observed by MASSON, PAS, and HE staining of renal tissues as well as the level of urine albumin/creatinine ratio (UACR). Mouse feces were collected for the 16S rRNA sequencing before and after the EMPA administration. Fecal short-chain fatty acids (SCFAs) and fecal and serum lipopolysaccharide (LPS) were determined, respectively.Keywords: empagliflozin, diabetic nephropathy, gut microbiota, 16S rRNA sequencing