Antibiotic Exposure Disturbs the Gut Microbiota and Its Metabolic Phenotype Differently in Rats with Advanced-Stage Type 1 Diabetes and Age-Matched Controls.

Antibiotic-induced microbial perturbations alter host metabolism and affect host physiology. In this study, we aimed to investigate the effects of vancomycin (Vanc) and ciprofloxacin/metronidazole (CiMe) exposures on the gut microbiome and metabolome in the colonic content and tissue samples from advanced-stage type 1 diabetic (AST1D) rats and age-matched controls (AMCs) using 16S ribosomal RNA gene sequencing and nuclear magnetic resonance-based metabolomics. The results show that antibiotic effects on the gut microbiota were stronger in AMC rats relative to AST1D rats. These microbial alterations were accompanied by a series of metabolic changes, including energy metabolism, short-chain fatty acid metabolism, and amino acid metabolism. We found that AMC rats had a more notable metabolic response to antibiotic exposure than AST1D rats. Additionally, Vanc had a stronger impact on the gut microbiota and host metabolic phenotype versus CiMe. Therefore, our results reveal that antibiotic-induced shifts in the gut microbiome and metabolome are different between AST1D and AMC rats. If confirmed in human studies, these findings suggest that diabetic patients may need a specific strategy for antibiotic use in clinical practice.