The differential effects of dupilumab and Janus kinase 1-selective inhibitors on the skin microbiome in adult patients with moderate-to-severe atopic dermatitis using metagenomic sequencing: results from the BioDay registry

Abstract Background The skin microbiome in atopic dermatitis (AD) is characterized by decreased bacterial diversity and increased Staphylococcus aureus colonization. Although dupilumab has been shown to improve the skin microbiome in adult AD patients, little is known about the effects of Janus kinase 1-selective inhibitors (JAK1-i). Therefore, the aim of this study was to evaluate the differential effects of dupilumab and JAK1-i on the skin microbiome of adult AD patients. Skin swabs were collected from dupilumab-treated patients (N = 10) lesional/facial at baseline (T0) and week 16 (T16), from JAK1-i-treated patients (N = 15) lesional/facial at T0, week 4 (T4) and week 28 (T28), and from healthy controls (HCs; N = 17) at a single time point. Shotgun metagenomic sequencing was used to assess microbial composition and diversity. Results During both treatments, the Eczema Area and Severity Index (EASI) scores significantly decreased over time (both p < 0.01), reflecting clinical response. In lesional/facial skin, S. aureus abundance significantly decreased after 16 weeks of dupilumab, whereas a nonsignificant decrease was observed after 28 weeks of JAK1-i. Microbial diversity increased in dupilumab-treated patients, approaching levels observed in HCs, while no such shift occurred during JAK1-i treatment. In both groups, commensal bacteria and fungi remained less abundant than in HCs. Conclusions Despite comparable clinical improvements, dupilumab induced a more pronounced shift in the skin microbiome towards healthy skin compared with JAK1-i.