Analyzing differences in gut microbiota in secondary failure of sulfonylureas through 16S rDNA sequencing and metabolomics

Currently, sulfonylureas, a class of medications used in type 2 diabetes mellitus (T2DM) treatment, are widely applied, but the problem of secondary failure isn't fully understood. This study aims to explore the potential mechanisms of secondary failure of sulfonylureas (SFS ) and to identify reliable predictive biomarkers. In this study, 16S rDNA sequencing technology and non-targeted metabolomics were used to analyze the differences in gut microbiota and metabolic products between the SFS and sulfonylurea effective (SE) groups. The results of 16S rDNA sequencing indicated that there are differences in composition between two groups. Seventeen different bacterial types were identified, including six types from SFS patients and eleven from SE. SFS might be linked to disturbances in energy metabolism, amino acid metabolism, nucleotide metabolism, and lipid metabolism within the gut microbiota. Metabolomics results showed 66 different metabolites between two groups (49 metabolites were upregulated, and 17 metabolites were downregulated). Correlation analysis between gut bacteria and fecal metabolites revealed that 4 types of gut bacteria were significantly linked to 5 types of metabolites. This study reveals distinct gut microbiota composition in patients with sulfonylurea secondary failure, helping us understand changes in gut metabolites and providing new biomarkers for personalized treatment.