Effect of Housing Condition and Diet on the Gut Microbiota of Weanling Immunocompromised Mice

Gastrointestinal microbiota are affected by a wide variety of extrinsic and intrinsic factors. In the husbandry of laboratorymice and design of experiments, controlling these factors where possible provides more reproducible results. However, themicrobiome is dynamic, particularly in the weeks immediately after weaning. In this study, we characterized the baselinegastrointestinal microbiota of immunocompromised mice housed under standard conditions for our facility for 6 weeks afterweaning, with housing either in an isolator or in individually ventilated cages and a common antibiotic diet (trimethoprimsulfamethoxazole). We compared these conditions to a group fed a standard diet and a group that was weaned to a standard diet then switched to antibiotic diet after 2 weeks. We found no clear effect of diet on richness and α diversity of the gastrointestinal microbiota. However, diet did affect which taxa were enriched at the end of the experiment. The change to antibiotic diet during the experiment did not convert the gastrointestinal microbiome to a state similar to mice consistently fed antibiotic diet, which may highlight the importance of the initial post-weaning period in the establishment of the gastrointestinal microbiome. We also observed a strong effect of housing type (isolator compared with individually ventilated cage) on the richness, α diversity, β diversity, and taxa enriched over the course of the experiment. Investigating whether the diet or microbiome affects a certain strain’s phenotype is warranted in some cases. However, our findings do not suggest that maintaining immunocompromised mice on antibiotic feed has a clinical benefit when potential pathogens are operationally excluded, nor does it result in a more consistent or controlled microbiome in the post-weaning period.