Therapeutic responses to Roseomonas mucosa 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 Roseomonas mucosa 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 R. mucosa 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, R. mucosa treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced Staphylococcus aureus burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to R. mucosa treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by R. mucosa 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 R. mucosa, 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 R. mucosa treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.

Authors

Myles, Ian A; Castillo, Carlo R; Barbian, Kent D; Kanakabandi, Kishore; Virtaneva, Kimmo; Fitzmeyer, Emily; Paneru, Monica; Otaizo-Carrasquero, Francisco; Myers, Timothy G; Markowitz, Tovah E; Moore, Ian N; Liu, Xue; Ferrer-Alegre, Marc; Sakamachi, Yosuke; Garantziotis, Stavros; Swamydas, Muthulekha; Lionakis, Michail S; Anderson, Erik D; Earland, Noah J; Ganesan, Sundar; Sun, Ashleigh A; Bergerson, Jenna R E; Silverman, Robert A; Petersen, Maureen; Martens, Craig A; Datta, Sandip K;

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