[Construction of a butyrate-producing engineered bacteria and its therapeutic effects on atopic dermatitis]

Objective Dysregulation of the gut-skin axis caused by intestinal microbiota imbalance is an important contributor to the pathogenesis of atopic dermatitis (AD). This study aims to construct an engineered Escherichia coli Nissle 1917 (EcN) strain capable of efficient and stable butyrate secretion, and evaluate its therapeutic efficacy in a calcipotriol (MC903)-induced mouse model of AD. Methods Using synthetic biology strategies, the core butyrate synthesis gene modules (bcd, but) derived from Faecalibacterium prausnitzii were codon-optimized, cloned into an expression plasmid, and introduced into the probiotic chassis strain Escherichia coli Nissle 1917 (EcN) by electroporation to generate the butyrate-producing engineered strain EcN-But. Butyrate yield was quantified via High-Performance Liquid Chromatography (HPLC), and genetic stability was rigorously assessed. An MC903-induced AD mouse model was established and treated with oral EcN-But. Therapeutic efficacy was evaluated through Eczema Area and Severity Index (EASI) scores, histological analysis (HE staining), serum IgE levels, and RT-qPCR analysis of cutaneous inflammatory cytokines including interleukin 4 (IL-4), IL-13, IL-33, thymic stromal lymphopoietin (TSLP) and tumor necrosis factor α (TNF-α). Results The engineered strain EcN-But was successfully constructed, achieving a stable butyrate secretion of (326.30±19.8)mg/L under anaerobic fermentation without significant metabolic burden on bacterial growth. In vivo, oral administration of EcN-But significantly reduced EASI scores and inhibited epidermal hyperplasia. Furthermore, EcN-But treatment significantly downregulated serum total IgE levels and suppressed the expression of key inflammatory cytokines in skin tissues. Conclusion The engineered strain EcN-But effectively alleviates AD-like inflammation by enabling in situ butyrate secretion in the gut to modulate systemic immune homeostasis, offering a novel live biotherapeutic product strategy for the clinical management of atopic dermatitis.