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Cutaneous SCFAs are reduced in infants with atopic dermatitis, and the SCFA-sensing receptor GPR43 modulates skin barrier integrity and inflammation [Human_RNA-seq]

ABSTRACT: Background: Early-life skin colonization by commensal microbes is associated with reduced risk of atopic dermatitis (AD), but underlying mechanisms remain unclear. Short-chain fatty acids (SCFAs), gut microbiome-derived metabolites with immunomodulatory functions, are also produced by cutaneous commensals, yet the roles of cutaneous SCFAs and their sensing receptor GPR43 in AD remain unclear. Methods: SCFA levels were quantified in non-lesional skin of infants with AD and controls. GPR43 expression was analyzed in flaky tail (Flgft) mice and human AD skin. The functional effects of GPR43 activation were evaluated in human keratinocytes and in vivo in Flgft mice using a GPR43 agonist. Results: Propionate and butyrate levels were reduced in non-lesional skin of infantile AD. Epidermal GPR43 expression was decreased in early life in Flgft mice. In keratinocytes, GPR43 was upregulated by differentiation, SCFAs, and type 2 cytokines. GPR43 activation promoted keratinocyte differentiation and long-chain ceramide synthesis, and attenuated IL-4/IL-13–induced barrier dysfunction and TSLP expression. Topical GPR43 agonist improved barrier function and reduced dermatitis in Flgft mice. Conclusion: Dysregulation of the SCFA–GPR43 axis occurs in the skin during early life in AD. Cutaneous GPR43 activation enhances barrier integrity and suppresses inflammation, suggesting a potential therapeutic strategy in AD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE336072 | GEO | 2026/08/24

REPOSITORIES: GEO

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Cutaneous SCFAs are reduced in infants with atopic dermatitis, and the SCFA-sensing receptor GPR43 modulates skin barrier integrity and inflammation

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