The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA.
Lab Anim (NY). 2021 Jul;50(7):185-195. doi: 10.1038/s41684-021-00777-0. Epub 2021 Jun 14.
Animal models play a critical role in establishing causal relationships between gut microbiota and disease. The laboratory mouse is widely used to study the role of microbes in various disorders; however, differences between mouse vendors, genetic lineages and husbandry protocols have been shown to contribute to variation in phenotypes and to non-reproducibility of experimental results. We sought to understand how gut microbiome profiles of mice vary by vendor, vendor production facility and health status upon receipt into an academic facility and how they change over 12 weeks in the new environment. C57BL/6 mice were sourced from two different production sites for each of three different vendors. Mice were shipped to an academic research vivarium, and fresh-catch stool samples were collected from mice immediately from the shipping box upon receipt, and again after 2, 6 and 12 weeks in the new facility. Substantial variation in bacterial proportional abundance was observed among mice from each vendor at the time of receipt, but shared microbes accounted for most sequence reads. Vendor-specific microbes were generally of low abundance. Microbial profiles of mice from all vendors exhibited shifts over time, highlighting the importance of environmental conditions on microbial dynamics. Our results emphasize the need for continued efforts to account for sources of variation in animal models and understand how they contribute to experimental reproducibility.
动物模型在确定肠道微生物群与疾病之间的因果关系方面起着至关重要的作用。实验室小鼠被广泛用于研究微生物在各种疾病中的作用;然而,研究表明,小鼠供应商、遗传谱系和饲养方案之间的差异会导致表型的变化,并导致实验结果的不可重现性。我们试图了解在进入学术设施时,供应商、供应商生产设施和健康状况如何影响小鼠的肠道微生物组谱,以及它们在新环境中 12 周内如何变化。我们从三个不同供应商的每个供应商的两个不同生产地点获取 C57BL/6 小鼠。将小鼠运往学术研究动物设施,在收到后立即从运输箱中收集新鲜粪便样本,并在新设施中 2、6 和 12 周后再次收集。在收到时,每个供应商的小鼠之间观察到细菌比例丰度存在大量差异,但共享的微生物占大多数序列读数。每个供应商的特定微生物通常丰度较低。来自所有供应商的小鼠的微生物谱随着时间的推移发生了变化,突出了环境条件对微生物动态的重要性。我们的结果强调了需要继续努力解释动物模型中的变异来源,并了解它们如何导致实验重现性。