Culture supernatants from human-derived commensal bacteria alleviate DNCB-induced atopic dermatitis through modulation of inflammatory and barrier-associated pathways

IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, impaired epidermal barrier function, and recurrent episodes of itching and inflammation. Emerging evidence suggests that skin-resident microbiota influence host immune responses and may modulate AD pathogenesis. Here, we investigated the anti-inflammatory, barrier-restoring, and neuro-supportive effects of culture supernatants (CSs) derived from skin-resident bacteria.MethodsHuman keratinocytes (HaCaT) stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were treated with CSs from various isolates. For in vivo evaluation, a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was utilized, receiving topical applications of the CSs. Furthermore, differentiated SH-SY5Y neuronal cells were treated with keratinocyte- or fibroblast-conditioned media, prepared after stimulation with bacterial CSs, to evaluate their neurotrophic potential.ResultsCSs from Brachybacterium paraconglomeratum and Brevibacterium casei significantly suppressed interleukin-6 (IL-6) and C-C motif chemokine ligand 17 (CCL17) while restoring filaggrin expression. In keratinocytes and human dermal fibroblasts, these CSs increased brain-derived neurotrophic factor (BDNF) expression. In the DNCB-induced AD-like mouse model, topical application of B. paraconglomeratum and B. casei CSs reduced epidermal hyperplasia and immune cell infiltration, downregulated tyrosine hydroxylase (TH), and restored cutaneous BDNF, glial cell line-derived neurotrophic factor (GDNF), and filaggrin (FLG) expression. In differentiated SH-SY5Y neuronal cells, the conditioned media treatments markedly upregulated BDNF, GDNF, and nerve growth factor (NGF). Mechanistically, CS treatment inhibited p38 MAPK and JAK–STAT signaling.DiscussionCollectively, these findings demonstrate that specific skin-derived bacterial metabolites exert coordinated anti-inflammatory, barrier-reinforcing, and neurotrophic activities, thereby promoting associated changes in neurotrophic markers. Such microbial products may serve as promising biologic candidates for managing atopic dermatitis.