Evaluating the Impact of Prophylactic Administration of Ivermectin on the Fecal Microbiome of Healthy C57BL/6J Mice (Mus musculus).

Upon importation, laboratory mice may undergo prophylactic antiparasitic treatment during quarantine to prevent the introduction of parasites into established colonies. While quarantine protocols vary across institutions, ivermectin is commonly used, administered either orally or topically. However, the impact of these practices on the fecal microbiome remains poorly understood, raising concerns about unintended consequences for experimental outcomes. This study investigated the effects of ivermectin on fecal microbiome composition in naïve, healthy male and female C57BL/6J mice. Animals received either ivermectin-impregnated feed (12 ppm, ad libitum for 4 weeks), weekly topical ivermectin solution (2.0 mg/kg for 4 weeks), or no treatment (controls). Fecal samples were collected for 16S rRNA-based microbiome analysis before ivermectin treatment, immediately posttreatment, and 4 weeks after treatment cessation. Weekly body weights were recorded, and histopathologic evaluation of the small intestine and colon was performed at study completion. Both oral and topical ivermectin treatments resulted in significant alterations in microbiome α and β diversity at the end of treatment, with more pronounced effects observed in female mice. Some of these changes persisted for up to 4 weeks after treatment cessation. Furthermore, the findings indicate a sex-specific effect of ivermectin on specific bacterial orders, with Bacillales predominantly affected in male mice, whereas Coriobacteriales and Bacteriodales were primarily impacted in female mice. During treatment, males receiving topical ivermectin weighed significantly less than controls, while females receiving dietary ivermectin weighed significantly more. Histopathological analysis revealed no abnormalities in intestinal tissues across all groups at 4 weeks posttreatment. These findings demonstrate that ivermectin administration induces measurable and persistent changes in the fecal microbiome of healthy mice. Researchers should consider these effects when designing experiments, and institutions must weigh the benefits of colony protection against potential microbiome-related confounding variables.