Computational insights into streptococcus as a driver of pediatric atopic dermatitis via skin, oral, and nasal cross-transmission

Summary: Abstract Body: Pediatric atopic dermatitis affects up to 20% of children globally, yet its pathogenesis remains poorly understood. While Staphylococcus aureus and Staphylococcus epidermidis are established contributors to adult AD, the role of the skin microbiome in pediatric AD remains underexplored, particularly given the distinct microbial composition of infants and young children. Here, we investigate Streptococcus (Strep), a dominant genus in pediatric oral, nasal, and skin microbiomes, and its potential role in AD pathogenesis. Through a multi-omic analysis of 503 16S rRNA sequencing samples and 208 shotgun metagenomes from three independent pediatric cohorts (ages 3 months to 4 years in San Diego, South Africa, and Singapore), we identified a striking enrichment of Strep species on lesional AD skin, with relative abundances exceeding 20% compared to ~10% in non-lesional skin and <5% in healthy controls. Source tracking using FEAST traced the origin of Strep strains on the skin to oral and nasal microbiomes of paired samples, implicating these sites as reservoirs of transmission likely facilitated by frequent hand-to-skin contact. A Random Forest model validated Strep as a discriminatory feature for lesional AD skin, achieving high accuracy in separating lesional, non-lesional, and healthy skin microbiomes. Strain-level analysis revealed shared Strep strains between the skin and oral or nasal microbiomes in children with AD, suggesting cross-microbiome transmission. Metagenomic profiling identified enrichment of protease- and toxin-associated genes in Strep strains isolated from lesional skin, suggesting potential functional adaptations contributing to inflammation and barrier dysfunction. The presence of Strep in the pediatric skin microbiome and its functional potential offer insight into why children are more commonly afflicted with AD and provide microbial targets to improve outcomes for affected families. Yang Chen¹, Teruaki Nakatsuji¹, Anna D. Nguyen¹, Felix S. Dube², Chris Dupont³, Richard L. Gallo¹ 1. Dermatology, University of California San Diego, La Jolla, CA, United States. 2. University of Cape Town Faculty of Science, Rondebosch, WC, South Africa. 3. J Craig Venter Institute, San Diego, CA, United States. Innate Immunity, Microbiology, and Microbiome