Acute and long-term effects of antibiotics commonly used in laboratory animal medicine on the fecal microbiota

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RESEARCH ARTICLE

Acute and long‑term effects of antibiotics commonly used in laboratory animal medicine on the fecal microbiota Scott W. Korte1, Rebecca A. Dorfmeyer2,3, Craig L. Franklin2,3,4 and Aaron C. Ericsson2,3,4* 

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. Introduction 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. When mouse models are used to study a disease process occurring in humans, a common practice is to strive for uniformity within the genetic background and environment of mice, by using inbred strains and providing a uniform diet, water, and housing to all mice. Moreover, all recognized infectious agents are excluded from many research

*Correspondence: [email protected] 2 Metagenomics Center, University of Missouri, Columbia, MO, USA Full list of author information is available at the end of the article

colonies through the use of extensive sentinel screening, quarantine, and procedural programs. Despite all of these efforts however, the gut microbiota (GM) likely represents a significant source of residual biological variability and as such, has gained the attention of many researchers as a variable that should be acknowledged and considered in experimental design [1, 2]. The trillions of bacteria residing within the gut of our research animals