Abstract
BackgroundAntibiotic therapy is commonly used in animal agriculture. Antibiotics excreted by the animals can contaminate farming environments, resulting in long term exposure of animals to sub-inhibitory levels of antibiotics. Little is known on the effect of this exposure on antibiotic resistance. In this study, we aimed to investigate the long term effects of sub-inhibitory levels of antibiotics on the gut microbiota composition and resistome of veal calves in vivo.Forty-two veal calves were randomly assigned to three groups. The first group (OTC-high) received therapeutic oral dosages of 1 g oxytetracycline (OTC), twice per day, during 5 days. The second group (OTC-low) received an oral dose of OTC of 100–200 μg per day during 7 weeks, mimicking animal exposure to environmental contamination. The third group (CTR) did not receive OTC, serving as unexposed control. Antibiotic residue levels were determined over time. The temporal effects on the gut microbiota and antibiotic resistance gene abundance was analysed by metagenomic sequencing.ResultsIn the therapeutic group, OTC levels exceeded MIC values. The low group remained at sub-inhibitory levels. The control group did not reach any significant OTC levels. 16S rRNA gene-based analysis revealed significant changes in the calf gut microbiota. Time-related changes accounted for most of the variation in the sequence data. Therapeutic application of OTC had transient effect, significantly impacting gut microbiota composition between day 0 and day 2. By metagenomic sequence analysis we identified six antibiotic resistance genes representing three gene classes (tetM, floR and mel) that differed in relative abundance between any of the intervention groups and the control. qPCR was used to validate observations made by metagenomic sequencing, revealing a peak of tetM abundance at day 28–35 in the OTC-high group. No increase in resistance genes abundance was seen in the OTC-low group.ConclusionsUnder the conditions tested, sub-therapeutic administration of OTC did not result in increased tetM resistance levels as observed in the therapeutic group.
Highlights
Antibiotic therapy is commonly used in animal agriculture
We did detect elevated levels in the samples taken at the Discussion In this study we aimed to investigate the effects of long term exposure to a low dose of oxytetracycline (OTC)
Based on 16S rDNA sequence analysis, we observed that antibiotic administration did not cause drastic changes in the composition of the gut microbiome of calves
Summary
Antibiotic therapy is commonly used in animal agriculture. Antibiotics excreted by the animals can contaminate farming environments, resulting in long term exposure of animals to sub-inhibitory levels of antibiotics. We aimed to investigate the long term effects of sub-inhibitory levels of antibiotics on the gut microbiota composition and resistome of veal calves in vivo. Selection mechanisms for resistance at sub-inhibitory concentrations are different from those active in the presence of lethal antibiotic concentrations [7]. Exposure to very low concentrations of antibiotics – even below the minimum inhibitory concentration (MIC) – elicits an adaptive resistance response [8], and can result in the presence of a wider range of resistant mutants, increased genotypic [9] and phenotypic [8] diversity, and higher rates of mechanisms that allow spreading of resistance, such as horizontal gene transfer (HGT) [10]. It has been shown that resistance mutations in bacteria exposed to sub-MIC antibiotic concentrations are different from those of bacteria exposed to high concentrations [11], supporting the presence of alternative resistance mechanisms
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