Microbiome analysis of AD patients treated with dupilumab

Background: Atopic dermatitis (AD) is associated with an altered skin microbiome and both lesional and nasal Staphylococcus aureus (S. aureus) colonization. Dupilumab treatment showed to reduce skin inflammation and therefore AD signs and symptoms, but it is also associated with facial adverse events (AEs). Objectives: To evaluate the effect of dupilumab treatment on the microbiome of AD patients and to investigate clonality of S. aureus strains present on lesional and facial skin, and anterior nares. Methods: Lesional, facial and nasal swabs were taken from AD patients at baseline (T0) and after 4 (T4) and 28 (T28) weeks of dupilumab treatment. AD severity was measured with the Eczema Area and Severity Index (EASI). Relative abundance, microbial diversity and differential abundances (DA) were analysed using 16s rRNA gene sequencing. Data were compared with non-atopic healthy controls (HCs). Whole genome sequencing (WGS) was performed on S. aureus cultures. Results: In total, 31 AD patients and 30 matched HCs were included. The mean EASI significantly decreased from 17.0 (SD 11.1) at T0 to 8.2 (SD 5.6) and 3.9 (SD 2.9) at T4 and T28, respectively (p<0.001). In lesional skin, the mean relative abundance of S. aureus significantly decreased from 43.1% at T0 to 5.3% at T28, , with S. aureus abundance having an opposite effect with the second most abundant species C. acnes. Both the inverse Simpson and Shannon index revealed an increase in microbial diversity between T0 and T28 (p<0.05), where the latter was comparable to HCs. Bray-Curtis dissimilarities showed a significant decrease in mean dissimilarity between HC and T0 versus T4/T28 samples. Similar changes, although mostly non-significant, were found in the facial microbiome of AD patients. No clear differences were observed in S. aureus abundance in the nose during treatment, while WGS revealed that S. aureus strains were mostly clonal within patients and across different body regions, irrespective of treatment. Conclusion: The lesional skin microbiome, and to a lesser extent the facial microbiome, of AD patients shifted towards healthy skin during 28-weeks of dupilumab treatment. No clear effect was found on S. aureus abundance in the nose and the nasal microbiome.