Skin microbiome in atopic dermatitis: New insights from clinical trials.

Abstract

Atopic dermatitis (AD) is a chronic skin inflammatory disorder, with extensive burden among both children and adults.1 Recent advances in mechanistic understanding of underlying inflammatory pathways associated with AD phenotypes have resulted in improved options for topical and systemic treatment,2 with efficacy of monotherapies (e.g. abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab, upadacitinib) ranging from 56.7% to 83.6%.3 Progression of AD is influenced by a combination of genetic, environmental and microbial covariates, and several studies have demonstrated the potential role of skin resident microbial flora (especially the bacterium Staphylococcus aureus) in AD,4 which may also impact response to therapy. Pertinent to this topic, Rauer et al.5 present their results from microbiome analysis of skin samples collected from patients with AD in the current issue of The Journal of the European Academy of Dermatology and Venereology. The authors analyzed baseline demographic and microbiome data from 60 moderate-to-severe AD patients from a previously reported cohort in New York, USA, to investigate correlation between disease severity and composition of the skin microbiome. Skin microbiome was sampled by swabbing lesional and adjacent non-lesional skin, and characterized by sequencing hypervariable regions V1–V3 of the 16S rRNA gene. Severity of AD was determined using SCORAD (SCORing Atopic Dermatitis), the validated clinical tool used to assess the extent and severity of eczema. Rauer et al. used objective SCORAD (oSCORAD, which considers only extent and intensity of AD) to determine correlation of AD severity with microbiome. These authors reported the skin microbiome of AD patients was dominated by S. aureus, which was detected in 79% of samples and was the most abundant species in 49% of lesional and 28% of non-lesional samples. Interestingly, diversity of skin microbiome correlated with oSCORAD, with lower diversity in lesional skin compared to non-lesional skin. High AD severity was associated with low evenness (a key determinant of microbiome composition), independent of skin sampling location. These results indicate dysbiosis in the microbiome population in lesional skin. Moreover, these authors identified S. aureus as a major contributor to association of microbiome diversity with AD severity and AD-affected skin sites. Among clinical variables, ethnicity was found to be an important covariate in the association between AD severity and skin microbiome. However, given the small sample size for sub-group analysis in the study, the contribution of ethnicity to skin microbiome and AD severity warrants further investigation. While elevated levels of S. aureus in the skin microbiome of AD patients have previously been reported,4 the study by Rauer et al.5 underscores the clinical relevance of this association as the samples were collected from patients at baseline of a well-designed clinical trial. Further analysis of skin microbiome during the progression of disease is likely to shed important insight into the interplay between changes in microbial composition and response to therapy. Given these interesting findings, a reasonable next step could be inclusion of skin microbiome sampling into clinical trials as exploratory endpoints in future clinical trials of AD. This would allow assessment if the identified microbial changes are linked with patient outcomes or medication response in a controlled setting. Ultimately this may then allow patient stratification based on microbial composition. Expanding those findings beyond the microbiome, such as targeting skin fungal mycobiome or virome may also reveal new insights into the contribution of microbial populations in AD. An important clinical implication of these results is that abundance of S. aureus may be used as a surrogate for skin microbial dysbiosis, especially since this organism may be more easily measured in a clinical setting using quantitative PCR rather than complete or complex microbiome analysis. Sequencing results can subsequently be obtained to analyze the microbiome, and used as a validation tool. The current study by Rauer et al.5 highlights key relationships between the skin microbiome and severity of AD, and will greatly inform ongoing efforts to develop new personalized therapeutic options for this disease. The authors have no conflicts of interest to declare. Data sharing is not applicable to this article as no new data were created or analyzed in this study.