Impact of Dupilumab on the Skin Microbiome in Children Aged 6–12 years with Moderate-to-Severe Atopic Dermatitis

Yan Liu,1,2 Shan Wang,1 Ying Liu,1 Dan Yu,3 Qing Wang,3 Yuanyuan Tian,1 Lin Ma1 1Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Department of Dermatology, Beijing Aerospace General Hospital, Beijing, People’s Republic of China; 3Laboratory of Infection and Microbiology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaCorrespondence: Lin Ma, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China, Email [email protected]: We aimed to investigate alterations in the skin microbiome following treatment and discontinuation of dupilumab in children with atopic dermatitis (AD).Methods: In all, 24 pediatric AD patients and 10 pediatric health volunteers (HVs) were included. AD patients were treated with dupilumab for 16 weeks and following by a 12-week discontinuation. Cutaneous samples were collected from HVs, and AD patients at baseline and during dupilumab application period (Week 2, Week 4, Week 8, Week 12, and Week 16) and discontinuation period (Week 22 and Week 28) to conduct sequencing targeting the 16s rRNA V3-V4 regions. Clinical severity was assessed using the Eczema Area and Severity Index (EASI), Individual Signs Score (ISS), Children’s Dermatology Life Quality Index scores (CDLQI), Patient Oriented Eczema Measure (POEM), and peak pruritus Numerical Rating Scale (NRS itch).Results: Dupilumab treatment significantly improved AD characteristics, with reductions in EASI, ISS, CDLQI, POEM, and NRS itch scores (all P < 0.01). Concurrently, 16s rRNA sequencing indicated decline in Staphylococcus aureus abundance and increase in microbial diversity. These changes began to reverse upon treatment discontinuation, coinciding with a trend toward worsening EASI scores. Moreover, a dupilumab-responsive reduction in other bacterial genera such as Aggregatibacter, and Megasphaera were observed; and these alterations could be reversed after treatment cessation.Conclusion: We provided a dynamical pattern of skin bacterial community during and after dupilumab therapy in pediatric AD patients. Our findings suggest that the therapeutic action of dupilumab may extend to modulating a wider range of bacteria than previously recognized. The roles of our identified candidate microbial taxa require further investigation in larger and functional studies.Keywords: atopic dermatitis, dupilumab, pediatrics, Staphylococcus aureus, microbiome