Environmental and skin–nasal microbiome variation in South African children with atopic dermatitis

Background/Objective: Atopic dermatitis (AD) in early childhood involves microbial dysbiosis. Skin and nasal microbiomes have been linked to AD severity, but not yet in an African cohort. Here, we aimed to explore how urban and rural stratification, disease severity, and inter-site bacterial overlap shape the skin and nasal microbiomes of children with AD in South Africa (ZA). Methods Children were recruited from urban Cape Town (CT) and rural Umtata (UM), ZA. We profiled the skin and nasal microbiomes of 197 children (87 healthy, 110 with AD; ages 12–36 months), totaling 502 samples, including both lesional and non-lesional skin sites in children with AD, in a cross-sectional study design. We used 16S rRNA V4–V5 sequencing for its accessibility and scalability to large sample sets. To address the limited species- and strain-level resolution of 16S data, we applied random forest (RF) machine-learning models to classify AD status with amplicon sequence variants (ASVs). We analyzed microbiome composition and diversity stratified by environment. Results We found that RF models could predict AD status using both skin and nasal microbiomes ( AUCs: skin = 0.70–0.82; nasal = 0.68 ), strongly driven by both Streptococcus and Staphylococcus . The correlations between skin–nasal microbiome were significantly stronger in children with AD compared to healthy controls, with overall higher correlations observed in rural UM (healthy r = 0.44 to AD r = 0.69 ) compared to urban CT (healthy r = 0.34 to AD r = 0.65 ). The skin microbiome diversity was higher in children from rural UM with healthy skin than those from urban CT ( p = 0.0012 ). However, children with AD in both groups showed significant alterations in their microbiome, with those in rural UM exhibiting greater beta diversity ( p = 0.001 ) than their urban CT counterparts ( p = 0.002 ). Conclusion In children with AD in South Africa, the environmental context is associated with microbial dysbiosis, and skin–nasal microbiomes reflect shared reservoirs. These findings highlight the value of geographically diverse studies with skin and mucocutaneous sampling in understanding pediatric AD.