Therapeutic responses to <i>Roseomonas mucosa</i> in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair.

Abstract

Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium <i>Roseomonas mucosa</i> for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of <i>R. mucosa</i> treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, <i>R. mucosa</i> treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced <i>Staphylococcus aureus</i> burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to <i>R. mucosa</i> treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by <i>R. mucosa</i> persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by <i>R. mucosa</i>, cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of <i>R. mucosa</i> treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.