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

J Proteome Res. 2019 Nov 1;18(11):3944-3954. doi: 10.1021/acs.jproteome.9b00402. Epub 2019 Oct 4.


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.

Keywords: BCAA; SCFA; antibiotic; diabetes; gut microbiota; metabolomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / classification
  • Bacteria / genetics
  • Colon / drug effects
  • Colon / metabolism
  • Diabetes Mellitus, Type 1 / metabolism*
  • Energy Metabolism / drug effects
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Humans
  • Male
  • Metabolome / drug effects*
  • Metabolomics / methods*
  • Phenotype
  • RNA, Ribosomal, 16S / genetics
  • Rats, Sprague-Dawley


  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S