Temporal relationships between Staphylococcus aureus colonization, filaggrin expression, and pediatric atopic dermatitis

Background: Atopic dermatitis (AD) is characterized by Staphylococcus aureus (S. aureus) colonization. Longitudinal early life data delineating relationships of S.aureus colonization, barrier function, and AD outcomes are lacking. We define longitudinal S.aureus endotypes and AD pathogenesis in early life. Methods: We defined longitudinal S. aureus skin colonization phenotypes across two annual visits (non-colonized: V1(-)V2(-), early transient: V1(+)V2(-), late-onset: V1(-)V2(+), persistent: V1(+)V2(+)) in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. We analyzed AD severity, sensitization, and skin barrier function across phenotypes, and performed mediation analyses between colonization and FLG expression. Results: Persistent S.aureus colonization was associated with increased SCORAD at V1 (33.5 vs. 19.0, p=.004) and V2 (40.1 vs.16.9, p<.001), and lower non-lesional (NL) FLG at V2 (1.77 vs. 4.09, p=.029) compared to the non-colonized phenotype, with early transient and late-onset colonization as intermediate phenotypes. Children colonized at V2 demonstrated a decrease in NL-FLG expression from V1 to V2 compared to those non-colonized at V2 (p=.0012), who maintained expression. This effect remained significant even after adjusting for V1 colonization and SCORAD (p=.011). Conclusions: Our findings are the first to present longitudinal quantitative FLG expression and S. aureus skin colonization in early life and suggest that a decrease in NL-FLG drives later colonization. Hence, therapies to maintain NL-FLG expression may prevent S.aureus colonization. Further, a longitudinal AD endotype of persistent colonization is characterized by increased AD severity, sensitization, and decreasing NL-FLG.

Automated summary

This study investigates the relationship between S.aureus colonization, FLG expression, and atopic dermatitis (AD) outcomes in children. The results suggest that persistent S.aureus colonization is associated with increased AD severity and sensitization, as well as decreased FLG expression in non-lesional skin cells.