Background

Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. Although alterations in the skin microbiome have been described in subjects with AD during progression to flare state, the prognostic value of baseline microbiome configurations has not been explored.

Objective

Our aim was to identify microbial signatures on AD skin that are predictive of disease fate.

Methods

Nonlesional skin of patients with AD and healthy control subjects were sampled at 2 time points separated by at least 4 weeks. Using whole metagenome analysis of skin microbiomes of patients with AD and control subjects (n = 49 and 189 samples), we identified distinct microbiome configurations (dermotypes A and B). Blood was collected for immunophenotyping, and skin surface samples were analyzed for correlations with natural moisturizing factors and antimicrobial peptides.

Results

Dermotypes were robust and validated across 2 additional cohorts (63 individuals), with strong enrichment of subjects with AD in dermotype B. Dermotype B was characterized by reduced microbial richness, depletion of Cutibacterium acnes, Dermacoccus and Methylobacterium species, individual-specific outlier abundance of Staphylococcus species (eg, S epidermidis, S capitis, S aureus), and enrichment in metabolic pathways (eg, branched chain amino acids and arginine biosynthesis) and virulence genes (eg, β-toxin, δ-toxin) that defined a pathogenic ecology. Skin surface and circulating host biomarkers exhibited a distinct microbial-associated signature that was further reflected in more severe itching, frequent flares, and increased disease severity in patients harboring the dermotype B microbiome.

Conclusion

We report distinct clusters of microbial profiles that delineate the role of microbiome configurations in AD heterogeneity, highlight a mechanism for ongoing inflammation, and provide prognostic utility toward microbiome-based disease stratification.

中文翻译：

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特应性皮炎微生物群分层为生态皮肤类型，使微生物毒力和疾病严重程度成为可能

背景

特应性皮炎 (AD) 是一种常见的皮肤病，影响全球 20% 的人口，具有显着的临床异质性，关于分子亚型和可操作的生物标志物的信息有限。尽管已经描述了 AD 受试者在进展到爆发状态期间皮肤微生物组的改变，但尚未探索基线微生物组配置的预后价值。

客观的

我们的目标是确定 AD 皮肤上可预测疾病命运的微生物特征。

方法

在相隔至少 4 周的 2 个时间点对 AD 患者和健康对照受试者的非病变皮肤进行取样。通过对 AD 患者和对照受试者（n = 49 和 189 个样本）的皮肤微生物组进行全宏基因组分析，我们确定了不同的微生物组配置（皮肤型 A 和 B）。收集血液进行免疫表型分析，分析皮肤表面样本与天然保湿因子和抗菌肽的相关性。

结果

Dermotypes是健壮和跨越2个额外的队列（63个个体）验证，与AD的受试者强烈富集在dermotype B. Dermotype B在其特征在于减少微生物的丰富性，耗尽Cutibacterium痤疮，Dermacoccus和Methylobacterium物种，个体特异性离群丰葡萄球菌属（如表皮葡萄球菌、头葡萄球菌、金黄色葡萄球菌）），以及定义致病生态学的代谢途径（例如，支链氨基酸和精氨酸生物合成）和毒力基因（例如，β-毒素、δ-毒素）的富集。皮肤表面和循环宿主生物标志物表现出独特的微生物相关特征，这进一步反映在皮肤型 B 微生物组患者更严重的瘙痒、频繁发作和疾病严重程度增加上。

结论

我们报告了不同的微生物群，这些群描述了微生物组配置在 AD 异质性中的作用，突出了持续炎症的机制，并为基于微生物组的疾病分层提供了预后效用。