Research on the mechanism of gut microbiota in reducing blood glucose of db/db diabetic mice by broad-spectrum antibiotics / 医学研究生学报

ABSTRACT

Objective The alterations of gut microbiota is closely related to metabolic diseases. The aim of this study was to analyze the effects of antibiotics on glucose metabolism and gut microbiota in mice, and to further explore the mechanism of gut microbiota in reducing blood glucose in db/db diabetic mice by broad-spectrum antibiotics. Methods 16 C57BL/KsJ-db/db mice were randomly divided into antibiotic group and control group with 8 mice in each group. Antibiotic group broad-spectrum antibiotics(vancomycin 10mg/(kg·d), carbenicillin 50mg/(kg·d), metronidazole 50mg/(kg·d), neomycin 30mg/(kg·d)); Control group 1% cellulose sodium solution as placebo treatment. Fasting blood glucose and body weights were recorded once a week during the study. At the same time, feces were collected for 16S rDNA gene sequencing analysis. The changes of fasting blood glucose, body weight, the relative abundance of microbiota, Shannon index, Simpson index and GLP-1 were compared between the two groups. Results After 5 weeks of treatment with broad-spectrum antibiotics (Vancomycin , Carbenicillin , Metronidazole , and Neomycin ), fasting blood glucose levels in db/db diabetic mice were significantly decreased (9.59±4.49mmol/L vs 19.71±8.74mmol/L,P=0.016). At the same time, antibiotics can also affect the gut microbiota of mice. The relative abundance of Proteobacteria in mice treated with antibiotics was significantly higher than that in control group (0.471±0.12 vs 0.177±0.12, P<0.05), and the OTUs of Proteobacteria, Enterobacteriaceae, Gamma-proteobacteria, and Enterobacteriales increased in mice treated with antibiotics compared with controls. In addition, we also showed antibiotics could change the diversity of gut microbiota, and the diversity of gut microbiota in antibiotic treated mice decreased significantly (Shannon index 3.135 vs 5.359, P<0.01); Simpson index 0.794 vs 0.946, P<0.01). Conclusion Broad-spectrum antibiotics can significantly reduce the fasting blood glucose level and the diversity of gut microbiota of db / db diabetic mice, and the alterations of gut microbiota may play an essential role in the process of reducing blood glucose by broad-spectrum antibiotics.