Developmental trajectories of atopic dermatitis with multi-omics approaches in the infant gut: COCOA birth cohort.

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.