Skin microbiome and its association with host cofactors in determining atopic dermatitis severity

Abstract

Background Atopic dermatitis (AD) is a heterogeneous, chronic inflammatory skin disease linked to skin microbiome dysbiosis with reduced bacterial diversity and elevated relative abundance of Staphylococcus aureus (S. aureus). Objectives We aimed to characterize the yet incompletely understood association between the skin microbiome and patients' demographic and clinical cofactors in relation to AD severity. Methods The skin microbiome in 48 adult moderate‐to‐severe AD patients was investigated using next‐generation deep sequencing (16S rRNA gene, V1–V3 region) followed by denoising (DADA2) to obtain amplicon sequence variant (ASV) composition. Results In lesional skin, AD severity was associated with S. aureus relative abundance (rS = 0.53, p < 0.001) and slightly better with the microbiome diversity measure Evenness (rS = −0.58, p < 0.001), but not with Richness. Multiple regression confirmed the association of AD severity with microbiome diversity, including Shannon (in lesional skin, p < 0.001), Evenness (in non‐lesional skin, p = 0.015) or S. aureus relative abundance (p < 0.012), and with patient's IgE levels (p < 0.001), race (p < 0.032), age (p < 0.034) and sex (p = 0.012). The lesional model explained 62% of the variation in AD severity, and the non‐lesional model 50% of the variation. Conclusions Our results specify the frequently reported “reduced diversity” of the AD‐related skin microbiome to reduced Evenness, which was in turn mainly driven by S. aureus relative abundance, rather than to a reduced microbiome Richness. Finding associations between AD severity, the skin microbiome and patient's cofactors is a key aspect in developing new personalized AD treatments, particularly those targeting the AD microbiome.

Skin microbiome in atopic dermatitis: New insights from clinical trials

“…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.…”

“…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.…”

“…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.…”

Functional heterogeneity of human skin‐resident memory T cells in health and disease

“…Recently, CLA + T cells were identified as superior producers of Th2 cytokines in the blood of a murine AD model 186 . Local microbiome disruption and Staphylococcus aureus colonization in AD have been shown to induce epithelial cytokine production, including IL‐33 and thymic stromal lymphopoietin which can modulate skin T RM phenotype and function 187,188 …”

Mild atopic dermatitis is characterized by increase in non-staphylococcus pathobionts and loss of specific species

“…These data indicate that other bacterial taxa could be involved in the pathogenesis of AD. So far, studies investigating the differences between the healthy and AD skin microbiome have included a limited age group (children or adults) and mostly focused on moderate-tosevere AD, while excluding AD patients with milder manifestations of disease (Byrd et al 2017;Chng et al 2016;Dekio et al 2007;Kong et al 2012;Rauer et al 2022). To gain better insights into the taxa important for the microbiome changes in mild AD manifestations, we need more studies including these patients and using next generation sequencing techniques, such as metagenomic sequencing, that can pro le their skin microbiome up to species level.…”