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

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

背景：在2型糖尿病（type 2 diabetes mellitus, T2DM）相关糖尿病肾病（diabetic nephropathy, DN）患者体内可观察到肠道菌群失调现象。作为糖尿病肾病的治疗药物，钠-葡萄糖协同转运蛋白2（sodium-glucose co-transporter 2, SGLT2）抑制剂据报道可对肠道菌群产生调控作用。本研究旨在明确作为SGLT2抑制剂的恩格列净（empagliflozin, EMPA）是否可通过调节肠道菌群来减轻糖尿病肾病的损伤。材料与方法：本研究采用高脂饮食（high-fat diet, HFD）联合链脲佐菌素（streptozocin, STZ）注射的方式，构建雄性C57BL/6J小鼠的糖尿病肾病模型。通过口服葡萄糖耐量试验（oral glucose tolerance test, OGTT）检测小鼠血糖水平。通过肾组织MASSON染色、PAS染色、HE染色结果以及尿白蛋白/肌酐比值（urine albumin/creatinine ratio, UACR）水平，观察恩格列净灌胃给药的治疗效果。分别在恩格列净给药前后收集小鼠粪便样本，进行16S rRNA测序检测。同时分别测定粪便短链脂肪酸（short-chain fatty acids, SCFAs）以及粪便、血清脂多糖（lipopolysaccharide, LPS）的水平。关键词：恩格列净，糖尿病肾病，肠道菌群，16S rRNA测序