Fundamental discoveries in many aspects of mammalian physiology have been made using laboratory mice as research models. These studies have been facilitated by the genetic tractability and inbreeding of such mice, the large set of immunological reagents that are available, and the establishment of environmentally controlled, high-throughput facilities. Such facilities typically include barriers to keep the mouse colonies free of pathogens and the frequent re-derivation of the mice severely limits their commensal flora. Because humans have co-evolved with microorganisms and are exposed to a variety of pathogens, a growing community of researchers posits that preclinical disease research can be improved by studying mice in the context of the microbiota and pathogens that they would encounter in the natural world. Here, we provide a perspective of how these different approaches can be combined and integrated to improve existing mouse models to enhance our understanding of disease mechanisms and develop new therapies for humans. We also propose that the term ‘mice with natural microbiota’ is more appropriate for describing these models than existing terms such as ‘dirty mice’.

哺乳动物生理学许多方面的基础发现都是使用实验室小鼠作为研究模型。这些研究得益于此类小鼠的遗传易处理性和近亲繁殖、可用的大量免疫试剂以及环境控制、高通量设施的建立。此类设施通常包括保持小鼠菌落免受病原体侵害的屏障，并且小鼠的频繁再衍生严重限制了它们的共生菌群。由于人类与微生物共同进化并暴露于各种病原体，因此越来越多的研究人员认为，可以通过在小鼠在自然界中遇到的微生物群和病原体的背景下研究小鼠来改进临床前疾病研究。在这里，我们提供了一个观点，说明如何结合和整合这些不同的方法以改进现有的小鼠模型，以增强我们对疾病机制的理解并为人类开发新的疗法。我们还提出，术语“具有天然微生物群的小鼠”比现有术语（如“脏小鼠”）更适合描述这些模型。