Streptozotocin-Induced Hyperglycemia Is Associated with Unique Microbiome Metabolomic Signatures in Response to Ciprofloxacin Treatment

It is well recognized that the microbiome plays key roles in human health, and that damage to this system by, for example, antibiotic administration has detrimental effects. With this, there is collective recognition that off-target antibiotic susceptibility within the microbiome is a particularly troublesome side effect that has serious impacts on host well-being. Thus, a pressing area of research is the characterization of antibiotic susceptibility determinants within the microbiome, as understanding these mechanisms may inform the development of microbiome-protective therapeutic strategies. In particular, metabolic environment is known to play a key role in the different responses of this microbial community to antibiotics. Here, we explore the role of host dysglycemia on ciprofloxacin susceptibility in the murine cecum. We used a combination of 16S rRNA sequencing and untargeted metabolomics to characterize changes in both microbiome taxonomy and environment. We found that dysglycemia minimally impacted ciprofloxacin-associated changes in microbiome structure. However, from a metabolic perspective, host hyperglycemia was associated with significant changes in respiration, central carbon metabolism, and nucleotide synthesis-related metabolites. Together, these data suggest that host glycemia may influence microbiome function during antibiotic challenge.