The Initial Gut Microbiota and Response to Antibiotic Perturbation Influence Clostridioides difficile Clearance in Mice.

The gut microbiota has a key role in determining susceptibility to infections (CDIs). However, much of the mechanistic work examining CDIs in mouse models uses animals obtained from a single source. We treated mice from 6 sources (2 University of Michigan colonies and 4 commercial vendors) with clindamycin, followed by a challenge, and then measured colonization levels throughout the infection. The microbiota were profiled via 16S rRNA gene sequencing to examine the variation across sources and alterations due to clindamycin treatment and challenge. While all mice were colonized 1 day postinfection, variation emerged from days 3 to 7 postinfection with animals from some sources colonized with for longer and at higher levels. We identified bacteria that varied in relative abundance across sources and throughout the experiment. Some bacteria were consistently impacted by clindamycin treatment in all sources of mice, including , , and To identify bacteria that were most important to colonization regardless of the source, we created logistic regression models that successfully classified mice based on whether they cleared by 7 days postinfection using community composition data at baseline, post-clindamycin treatment, and 1 day postinfection. With these models, we identified 4 bacterial taxa that were predictive of whether cleared. They varied across sources () or were altered by clindamycin () or both ( and ). Allowing for microbiota variation across sources better emulates human interindividual variation and can help identify bacterial drivers of phenotypic variation in the context of CDIs. is a leading nosocomial infection. Although perturbation to the gut microbiota is an established risk, there is variation in who becomes asymptomatically colonized, develops an infection, or has adverse infection outcomes. Mouse models of infection (CDI) are widely used to answer a variety of pathogenesis questions. However, the interindividual variation between mice from the same breeding facility is less than what is observed in humans. Therefore, we challenged mice from 6 different breeding colonies with We found that the starting microbial community structures and persistence varied by the source of mice. Interestingly, a subset of the bacteria that varied across sources were associated with how long was able to colonize. By increasing the interindividual diversity of the starting communities, we were able to better model human diversity. This provided a more nuanced perspective of pathogenesis.