Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis

Abstract

Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.

A systematic literature review of the human skin microbiome as biomarker for dermatological drug development

“…The skin microbiome in patients with AD was assessed in 11 studies, Table 1 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66. A greater proportion of longitudinal studies and 2 completed randomized controlled trials were performed in AD patients.…”

“…A greater proportion of longitudinal studies and 2 completed randomized controlled trials were performed in AD patients. There is general consensus across studies that skin affected by AD exhibits decreased bacterial diversity, as a result of an increased abundance of S. aureus 60, 61, 62, 63, 64, 66. In particular, AD flare ups were associated with an increased proportion of Staphyloccocus sequences, and S. aureus abundance correlated with disease severity 60.…”

“…There is general consensus across studies that skin affected by AD exhibits decreased bacterial diversity, as a result of an increased abundance of S. aureus 60, 61, 62, 63, 64, 66. In particular, AD flare ups were associated with an increased proportion of Staphyloccocus sequences, and S. aureus abundance correlated with disease severity 60. In line with these results, microbial diversity in AD lesions was inversely correlated with overall eczema severity as observed by the EASI 63, with several further studies also reporting taxonomic normalization and increased bacterial diversity in AD lesional skin, following various treatments 60, 61, 63, 66.…”

“…Currently, no evidence of benefit of antimicrobial interventions directed at reduction of Staphylococcus in patients with AD exists, only in secondarily impetiginized AD 69, 70, 71. As multiple studies included in this review indicate that the skin microbiota within an individual patient varies over time 60, 61, 63, 64, there is need for longitudinal, frequent sampling and standard analysis studies. Nevertheless, it has proven its potential value and is recommended to apply in AD clinical trials, in particular when microbiota can serve also as drug‐specific biomarker, i.e.…”

“…The standardization of controllable factors to reduce confounders was not well documented or maybe not performed in most of the included studies. As simple factors including but not limiting of age, ethnicity, environmental factors, soap use, hand‐washing and the use of topical (antimicrobial) agents before sampling have been shown to alter microbial skin communities; documentation of these metadata is essential to draw valid conclusions 5, 8, 12, 60, 61, 79, 80, 81. Multiple methods were used for skin microbiome sampling across the studies (i.e.…”