Therapeutic Responses to Roseomonas mucosa in Atopic Dermatitis Involve Lipid-Mediated TNF-related Epithelial Repair

Dysbiosis is increasingly implicated as a targetable contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of commensal R. mucosa for the treatment of AD in ten adults and five children older than 9 years of age. However, both mechanism of action and impacts on the most common age range for AD patients (less than 7 years of age) remained unexplored. We now show in patients as young as three years, R. mucosa treatment was associated with significant improvements in disease severity, barrier function, S. aureus burden, topical steroid requirements, and quality of life without any related adverse events. Our observed response rates were significantly greater than those seen in the placebo control groups of prior AD studies and similar to responses seen during open-label testing phase for currently approved topical treatments. Improvements and colonization persisted up to 8 months after cessation of treatment. Production of lipids in the sphingolipid pathway, cholinergic signaling, and flagellin expression accounted for modeled therapeutic impacts via induction of TNFR2-related epithelia-to-mesenchymal transition. These results support conduct of a placebo-controlled trial and suggest a role of commensals in maintenance of the epithelial barrier.