Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare
Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare
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DOI：
10.1038/nmicrobiol.2016.106
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发表时间：
2016-09-01
影响因子：
28.3
通讯作者：
Nagarajan, Niranjan
中科院分区：
文献类型：
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作者：
Chng, Kern Rei;Tay, Angeline Su Ling;Nagarajan, Niranjan
全宏基因组分析有可能揭示皮肤病的功能性触发因素，但成本、稳健性和采样效率等问题限制了其应用。在这里，我们建立了一种替代的，临床实用的和强大的宏基因组分析方案，并将其应用于80个皮肤微生物组样本流行病学分层的特应性皮炎（AD）。我们已经确定了不同的非耀斑，基线皮肤微生物组签名富集链球菌和Gemella，但耗尽了AD易感皮肤与正常健康皮肤中的Dermacoccus。使用角质形成细胞和单核细胞来源的树突状细胞的细菌攻击试验建立了不同的IL-1介导的，先天性和Th 1介导的适应性免疫反应与金黄色葡萄球菌和表皮葡萄球菌。细菌差异得到了真核生物群落扰动和微生物群全基因组功能变化的补充，这可能加剧AD易感皮肤中病原体生长和炎症的干燥和碱性表型。这些发现提供了关于皮肤微生物群落、皮肤表面微环境和免疫系统如何相互交叉调节，从而升级它们之间导致AD爆发的破坏性反馈循环的见解。
Whole metagenome analysis has the potential to reveal functional triggers of skin diseases, but issues of cost, robustness and sampling efficacy have limited its application. Here, we have established an alternative, clinically practical and robust metagenomic analysis protocol and applied it to 80 skin microbiome samples epidemiologically stratified for atopic dermatitis (AD). We have identified distinct non-flare, baseline skin microbiome signatures enriched for Streptococcus and Gemella but depleted for Dermacoccus in AD-prone versus normal healthy skin. Bacterial challenge assays using keratinocytes and monocyte-derived dendritic cells established distinct IL-1-mediated, innate and Th1-mediated adaptive immune responses with Staphylococcus aureus and Staphylococcus epidermidis. Bacterial differences were complemented by perturbations in the eukaryotic community and functional shifts in the microbiome-wide gene repertoire, which could exacerbate a dry and alkaline phenotype primed for pathogen growth and inflammation in AD-susceptible skin. These findings provide insights into how the skin microbial community, skin surface microenvironment and immune system cross-modulate each other, escalating the destructive feedback cycle between them that leads to AD flare.