BACKGROUND An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD. OBJECTIVE To determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms based on multi-omics analyses. METHODS Latent class trajectory analysis was used to AD phenotype in 2247 children who were followed until 9 years of age from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) birth cohort study. Multi-omics analyses (microbiome, metabolites, and gut epithelial cell transcriptome) using stool samples collected at 6 months of age were performed to elucidate the underlying mechanisms of AD phenotypes. RESULTS Five AD phenotypes were classified as follows: never/infrequent, early-onset transient, intermediate-transient, late-onset, and early-onset persistent. Early-onset persistent and late-onset phenotypes showed increased risks of food allergy and wheezing treatment ever, with bronchial hyperresponsiveness only evident in the early-onset persistent phenotype. Multi-omics analyses revealed a significantly lower relative abundance of Ruminococcus gnavus and a decreased gut acetate level in the early-onset persistent phenotype, with potential associations to ACSS2, JAK-STAT signaling, and systemic Th2 inflammation. The early-onset transient phenotype was associated with AMPK and/or chemokine signaling regulation, whereas the late-onset phenotype was linked with IL-17 and barrier dysfunction. CONCLUSIONS Multi-omics profiling in early life may offer insights into different mechanisms underlying AD phenotypes in children.

中文翻译：

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婴儿肠道多组学方法特应性皮炎的发育轨迹：COCOA 出生队列。


背景 了解特应性皮炎 （AD） 的表型和内型对于开发精准疗法至关重要。最近的研究证明了 AD 中肠-皮肤轴的证据。目的 确定 AD 表型的自然病程和临床特征，并在多组学分析的基础上探讨其机制。方法 对 2247 名儿童进行 AD 表型分析，这些儿童从 COhort 儿童哮喘和过敏性疾病起源 （COCOA） 出生队列研究中随访至 9 岁。使用在 6 月龄时收集的粪便样本进行多组学分析 （微生物组、代谢物和肠道上皮细胞转录组） 以阐明 AD 表型的潜在机制。结果 5 种 AD 表型分类如下： 从不/不频繁、早发性短暂、中度-短暂、晚发性和早发性持续性。早发性持续性和晚发性表型显示食物过敏和喘息治疗的风险增加，支气管高反应性仅在早发性持续表型中明显。多组学分析显示，在早发性持续性表型中，瘤胃球菌的相对丰度显著降低，肠道乙酸盐水平降低，可能与 ACSS2 、 JAK-STAT 信号传导和全身性 Th2 炎症有关。早发性瞬时表型与 AMPK 和/或趋化因子信号调节相关，而晚发性表型与 IL-17 和屏障功能障碍有关。结论 早期生命中的多组学分析可能为了解儿童 AD 表型的不同机制提供见解。