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

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

PROVIDER: PRJNA609668 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11213900_1.fastq.gz	Fastqsanger.gz
	SRR11213900_2.fastq.gz	Fastqsanger.gz
	SRR11213901_1.fastq.gz	Fastqsanger.gz
	SRR11213901_2.fastq.gz	Fastqsanger.gz
	SRR11213902_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

2020-09-23 | GSE146184 | GEO

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

Project description: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.

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mRNA expression of Atopic Dermatitis keratinocytes

Project description:mRNA array analysis of total RNA from primary kertinocytes from three healthy controls, three atopic dermatitis patients and three psoriasis patients was carried out

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Project description:Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. Serum from 8 children with AD and 8 healthy children were collected

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