The gut microbiota has a key role in determining susceptibility to Clostridioides difficile 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 C. difficile challenge, and then measured C. difficile 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 C. difficile challenge. While all mice were colonized 1 day postinfection, variation emerged from days 3 to 7 postinfection with animals from some sources colonized with C. difficile 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 Lachnospiraceae, Ruminococcaceae, and Enterobacteriaceae. 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 C. difficile 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 C. difficile cleared. They varied across sources (Bacteroides) or were altered by clindamycin (Porphyromonadaceae) or both (Enterobacteriaceae and Enterococcus). 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.

中文翻译：

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初始肠道微生物群和对抗生素扰动的反应影响小鼠艰难梭菌的清除

肠道微生物群在确定艰难梭菌感染 (CDI) 的易感性方面起着关键作用。然而，在小鼠模型中检查 CDI 的大部分机械工作使用从单一来源获得的动物。我们用克林霉素处理了来自 6 个来源（密歇根大学的 2 个菌落和 4 个商业供应商）的小鼠，然后进行了艰难梭菌攻击，然后测量了整个感染过程中的艰难梭菌定植水平。通过 16S rRNA 基因测序对微生物群进行了分析，以检查由于克林霉素处理和艰难梭菌引起的跨来源和改变的变异挑战。虽然所有小鼠都在感染后 1 天定植，但在感染后第 3 天至第 7 天出现变异，而来自某些来源的动物在更长时间和更高水平上定植艰难梭菌。我们确定了不同来源和整个实验过程中相对丰度不同的细菌。有些细菌一贯克林霉素治疗小鼠的所有来源，包括受影响的毛螺，Ruminococcaceae和肠杆菌。为了确定无论来源如何对定植最重要的细菌，我们创建了逻辑回归模型，该模型根据小鼠是否清除艰难梭菌成功地对小鼠进行分类到感染后 7 天，使用基线、克林霉素治疗后和感染后 1 天的群落组成数据。使用这些模型，我们确定了 4 个可预测艰难梭菌是否清除的细菌分类群。它们因来源（拟杆菌属）而异，或被克林霉素（卟啉单胞菌科）或两者（肠杆菌科和肠球菌）改变。允许跨来源的微生物群变异可以更好地模拟人类个体间变异，并有助于识别 CDI 背景下表型变异的细菌驱动因素。