Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.
Front Immunol. 2021 Mar 17;12:650621. doi: 10.3389/fimmu.2021.650621. eCollection 2021.
Epidemiological studies have long reported that perturbations of the childhood microbiome increase the risk of developing allergies, but a causal relationship with atopic dermatitis remains unclear. Here we colonized germ-free mice at birth or at one or eight week-of-age to investigate the role of prenatal and early postnatal microbial exposure on development of oxozolone-induced dermatitis later in life. We demonstrate that only one week delayed microbial colonization increased IgE levels and the total histological score of the inflamed ear compared to mice colonized throughout life. In parallel, several pro-inflammatory cytokines and chemokines were upregulated in the ear tissue demonstrating an enhanced immunological response following delayed postnatal colonization of the gut. In contrast, sensitivity to oxazolone-induced dermatitis was unaffected by the presence of a maternal microbiota during gestation. Mice colonized at eight week-of-age failed to colonize Rikenellaceae, a group of bacteria previously associated with a high-responding phenotype, and did not develop an immunological response to the same extent as the early colonized mice despite pronounced histopathological manifestations. The study provides proof-of-principle that the first intestinal colonizers of mice pups are crucial for the development of oxazolone-induced dermatitis later in life, and that the status of the maternal microbiota during pregnancy has no influence on the offspring's allergic immune response. This highlights an important window of opportunity following birth for microbiota-mediated interventions to prevent atopic responses later in life. How long such a window is open may vary between mice and humans considering species differences in the ontogeny of the immune system.
流行病学研究长期以来报告称，儿童微生物组的紊乱会增加过敏的风险，但与特应性皮炎之间的因果关系仍不清楚。在这里，我们在出生时或 1 或 8 周龄时对无菌小鼠进行定植，以研究产前和早期产后微生物暴露对生命后期氧化唑诱导性皮炎发展的作用。我们证明，与一生中定植的小鼠相比，仅延迟一周定植会增加 IgE 水平和发炎耳朵的总组织学评分。平行地，在耳朵组织中上调了几种促炎细胞因子和趋化因子，表明在延迟的肠道定植后，免疫反应增强。相比之下，怀孕期间母体微生物群的存在对氧化唑诱导的皮炎的敏感性没有影响。在 8 周龄定植的小鼠未能定植理研菌科，该科细菌以前与高反应表型有关，并且尽管有明显的组织病理学表现，但未像早期定植的小鼠那样发展出免疫反应。该研究提供了原理证明，即幼鼠的第一批肠道定植细菌对于生命后期氧化唑诱导性皮炎的发展至关重要，并且怀孕期间母体微生物群的状态对后代的过敏免疫反应没有影响。这强调了出生后，通过微生物群介导的干预来预防生命后期特应性反应的一个重要机会窗口。考虑到免疫系统的个体发育在不同物种之间存在差异，这种窗口开放的时间长短在老鼠和人类之间可能有所不同。
