Antibiotic treatment is widely used to combat bacterial infections. This can have detrimental consequences as antibiotics are not specific for pathogenic bacteria but can also cause long-lasting disruption of the gut microbiota. Previous work in our group did not find any detrimental consequences of antibiotic use on metabolic health, although inter-individual differences in response were observed. Here, we aimed to investigate this subject-specific response to antibiotic use by stratifying individuals based on the presence of antibiotic resistance genes (ARGs) or opportunistic pathogens (OP) in the baseline fecal microbiota.

Quantitative Polymerase Chain Reaction (qPCR) was used to determine presence of ARGs and OP in bacterial DNA isolated from fecal samples of 56 males with overweight/obesity (Body Mass Index: 25-35 kg/m²) and impaired glucose metabolism (fasting plasma glucose  5.6mmol/L and/or 2-hour glucose 7.8-11.1 mmol/L) at baseline and after 7-day vancomycin, amoxicillin or placebo treatment. Gut microbial composition was analyzed using the HITChip microarray. A two-step hyperinsulinemic-euglycemic clamp was used to determine tissue-specific insulin sensitivity. Adipose tissue gene expression was analyzed using Affymetrix microarray analysis.

At baseline, the vancomycin resistant gene vanB was present in 33 of 55 individuals. In the group carrying vanB at baseline, adipose tissue insulin sensitivity, defined as the insulin-mediated suppression of plasma free fatty acids, decreased during vancomycin use, while it improved in the vanB-absent group (% change after vs. baseline: -6,66+/-7,47 vs. 14,14+/-5,57% (p=0.042)). This decrease was accompanied by expansion of Enterococcus and Streptococcus, well-known vanB-carrying bacteria, in the gut microbiome. Conversely, in the vanB-absent group, inflammatory pathways were downregulated in subcutaneous adipose tissue after vancomycin use, while pathways involved in extracellular matrix remodeling were upregulated.

In conclusion, fecal carriage of vanB at baseline is predictive for vancomycin-induced metabolic response and is accompanied by deterioration of adipose tissue function, potentially resulting from expansion of vanB-resistant bacteria.