Animals and Experimental Design
Eight-week-old male C57BL/6J mice and KK-Ay diabetic mice (C57BL/6J background) purchased from Beijing Huafukang Biotechnology Co., Ltd. The animals were maintained at standard environmental conditions temperature 25 °C, humidity 50%, and free access to sterile food and water. After one week of acclimation, the mice were randomly divided into 5 groups with 6 mice in each group. C57BL/6J mice were fed with a standard diet and KK-Ay mice were fed with a high fat diet (HFD) for two weeks, and the blood glucose was measured and the mice with blood glucose≥11 mmol/L were selected as the diabetic model. The diabetic mice were randomly divided into four groups: (1) Model group, treated with the vehicle; (2) L-Dios group, treated with 20 mg/kg.d Dios; (3) H-Dios group, treated with 60 mg/kg.d Dios; (4) Metformin (Met) group, treated with 60mg/kg.d Met. For the experiment of Corynebacterium glutamicum( C. glu)transplantation, the diabetic mice were also randomly divided into four groups: (1) Model group, treated with the vehicle; (2) Dios group, treated with 60 mg/kg.d Dios; (3)C. glu group, treated with 5×109CFU/100ul/10gC. glu ; (4) Dios+C. glu group, treated with 60mg/kg.d Dios and 5×109CFU/100ul/10g C. glu for four weeks. During the treatment period, body weight and blood glucose levels were monitored weekly. On the last day of the experiment, fresh mouse stool samples were directly collected in the ultra-clean workbench and immediately stored at -80°C for subsequent analysis. Tissues including liver and skeletal muscle were carefully harvested and kept in liquid nitrogen and then stored at −80°C until analysis.