Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Department of Food Science, Faculty of Science, University of Copenhagen, Denmark.
Sci Rep. 2017 Mar 14;7:44385. doi: 10.1038/srep44385.
Atopic Dermatitis (AD) has been associated with gut microbiota (GM) dysbiosis in humans, indicating a causative role of GM in AD etiology. Furthermore, the GM strongly correlates to essential disease parameters in the well-known oxazolone-induced mouse model of AD. Here, we demonstrate that it is possible to transfer both a high-responding and a low-responding AD phenotype with GM from conventional mice to germ-free mice. The mice inoculated with the high-responding GM had significantly higher clinical score, increased ear thickness, and increased levels of IL-1β, TNFα, IL-4, IL-5, and IL-6 compared to the mice inoculated with the low-responding GM. The inter-individual variation was in general not affected by this increase in effect size. Germ-free mice induced with AD revealed a high disease response as well as high inter-individual variation indicating protective properties of certain microbial taxa in this model. This study underlines that the GM has a strong impact on AD in mouse models, and that the power of studies may be increased by the application of mice inoculated with a specific GM from high responders to increase the effect size.
特应性皮炎(AD)与人类肠道微生物群(GM)失调有关,表明 GM 在 AD 发病机制中起因果作用。此外,GM 与 AD 的公认 oxazolone 诱导的小鼠模型中的重要疾病参数密切相关。在这里,我们证明可以将来自常规小鼠的 GM 中的高反应性和低反应性 AD 表型转移到无菌小鼠中。与接种低反应性 GM 的小鼠相比,接种高反应性 GM 的小鼠的临床评分显著升高,耳部厚度增加,IL-1β、TNFα、IL-4、IL-5 和 IL-6 水平升高。这种效应大小的增加通常不会影响个体间的变异。用 AD 诱导的无菌小鼠表现出高疾病反应和高个体间变异,表明在该模型中某些微生物类群具有保护作用。这项研究强调了 GM 对小鼠模型中 AD 的强烈影响,并且通过应用来自高反应者的特定 GM 对无菌小鼠进行接种可以增加效应大小,从而提高研究的效力。