Abstract
Biomedical research relies on the use of animal models, and the animals used in those models receive medical care, including antibiotics for brief periods of time to treat conditions such as dermatitis, fight wounds, and suspected bacterial pathogens of unknown etiology. As many mouse model phenotypes are sensitive to changes in the gut microbiota, our goal was to examine the effect of antibiotics commonly administered to mice. Therefore, four treatment groups (subcutaneous enrofloxacin for 7 days, oral enrofloxacin for 14 days, oral trimethoprim-sulfamethoxazole for 14 days, and topical triple antibiotic ointment for 14 days) alongside a fifth control group receiving no treatment (n = 12/group) were included in our study. Fecal samples were collected prior to treatment, immediately after two weeks of exposure, and four weeks after cessation of treatment, and subjected to 16S rRNA library sequencing. The entire experimental design was replicated in mice from two different suppliers. As expected, several treatments including enrofloxacin and triple antibiotic ointment substantially decreased the amount of DNA recovered from fecal material, as well as the microbial richness. Notably, many of these effects were long-lasting with diminished gut microbiota (GM) richness four weeks following exposure, in both substrains of mice. Trimethoprim-sulfamethoxazole induced minimal to no discernible changes in the taxonomic composition beyond that seen in control mice. Collectively, these data highlight the need to consider the impact on GM of brief and seemingly routine use of antibiotics in the clinical care of research animals.
Highlights
Comparative medicine is predicated on the use of animal models to provide a better understanding of the human condition, and mouse models in particular have become the backbone of biomedical research
Triple antibiotic ointment and enrofloxacin are associated with decreased fecal biomass Review of the sequencing data generated from all 360 samples (2 mouse sources × 5 treatment groups × 3 time-points × 12 mice/group) revealed that seven samples failed to achieve a sufficient read count for use in downstream statistical analysis
Four of those seven failed samples were from a single treatment group and time-point (C57BL/6 J mice immediately after two weeks of treatment with triple antibiotic ointment), suggesting that the gut microbiota (GM) of this group was disproportionately affected by exposure to antibiotics
Summary
Comparative medicine is predicated on the use of animal models to provide a better understanding of the human condition, and mouse models in particular have become the backbone of biomedical research. Once mice arrive at a new research institution, many other factors including shipping and acclimation [5], method of water purification [6], diet, bedding, and caging [7] can induce subtle or substantial changes in the composition of the GM at different levels of the gastrointestinal tract. Enrofloxacin can be administered via intra-peritoneal (IP) injection, possibly providing a preferable route of administration with decreased direct exposure to, and influence on, the GM. Another commonly used antibiotic in mouse colonies is triple-antibiotic ointment (TAB) containing bacitracin, neomycin, and polymyxin B, with relatively broad activity against Gram-positive and Gram-negative organisms. We tested the influence of four different transient antibiotic treatments on the composition of the GM, sampling before antibiotic exposure, immediately after two weeks of exposure, and again four weeks after the discontinuation of treatment, with untreated mice serving as a control for time-dependent changes
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