Commensal Skin Bacteria Exacerbate Inflammation and Delay Skin Barrier Repair.

The skin microbiome can both trigger beneficial immune stimulation and pose a potential infection threat. Previous studies have shown that colonization of mouse skin with the model human skin commensal Staphylococcus epidermidis is protective against subsequent excisional wound or pathogen challenge. However, less is known about concurrent skin damage and exposure to commensal microbes, despite growing interest in interventional probiotic therapy. In this study, we address this open question by applying commensal skin bacteria at a high dose to abraded skin. Although depletion of the skin microbiome through antibiotics delayed repair from damage, probiotic-like application of commensals-including the mouse commensal Staphylococcus xylosus, 3 distinct isolates of S. epidermidis, and all other tested human skin commensals-also significantly delayed barrier repair. Increased inflammation was observed within 4 hours of S. epidermidis exposure and persisted through day 4, at which point the skin displayed a chronic wound-like inflammatory state with increased neutrophil infiltration, increased fibroblast activity, and decreased monocyte differentiation. Transcriptomic analysis suggested that the prolonged upregulation of early canonical proliferative pathways inhibited the progression of barrier repair. These results highlight the nuanced role of members of the skin microbiome in modulating barrier integrity and indicate the need for caution in their development as probiotics.

Commensal skin bacteria exacerbate inflammation and delay skin healing.

The skin microbiome can both trigger beneficial immune stimulation and pose a potential infection threat. Previous studies have shown that colonization of mouse skin with the model human skin commensal Staphylococcus epidermidis is protective against subsequent excisional wound or pathogen challenge. However, less is known about concurrent skin damage and exposure to commensal microbes, despite growing interest in interventional probiotic therapy. Here, we address this open question by applying commensal skin bacteria at a high dose to abraded skin. While depletion of the skin microbiome via antibiotics delayed repair from damage, application of commensals-- including the mouse commensal Staphylococcus xylosus, three distinct isolates of S. epidermidis, and all other tested human skin commensals-- also significantly delayed barrier repair. Increased inflammation was observed within four hours of S. epidermidis exposure and persisted through day four, at which point the skin displayed a chronic-wound-like inflammatory state with increased neutrophil infiltration, increased fibroblast activity, and decreased monocyte differentiation. Transcriptomic analysis suggested that the prolonged upregulation of early canonical proliferative pathways inhibited the progression of barrier repair. These results highlight the nuanced role of members of the skin microbiome in modulating barrier integrity and indicate the need for caution in their development as probiotics.

On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis.

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.

The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment.

Background: Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics. Objectives: To characterize changes in the skin microbiome during treatment for AD. Methods: The skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification. Results: We included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment. Conclusions: There are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.