Microbial-derived 2,3-butanediol restores epidermal barrier integrity through NF-κB signaling pathway inhibition and enhanced keratinocyte differentiation

Abstract

2,3-butanediol (2,3-BDO), produced through microbial fermentation, exhibits significant therapeutic potential for inflammatory skin disorders. This study demonstrates that 2,3-BDO suppresses NF-κB signaling in macrophages, inhibiting inflammatory mediators (nitric oxide, TNF-α, IL-6) with efficacy comparable to dexamethasone and D-panthenol. In macrophage-keratinocyte co-cultures, 2,3-BDO simultaneously attenuates inflammatory signals while promoting keratinocyte differentiation through upregulation of involucrin and cytokeratin 10. Ex vivo porcine skin models confirm that 2,3-BDO reduces inflammatory hyperplasia, suppresses aberrant keratinocyte proliferation, and restores barrier protein expression. 2,3-BDO’s distinctive mechanism involves concurrent inhibition of inflammatory cascades and enhancement of epidermal differentiation. This biocompatible molecule offers advantages over synthetic approaches, including reduced environmental impact and enhanced product purity. These findings establish 2,3-BDO as a promising therapeutic candidate for inflammatory skin conditions characterized by barrier dysfunction, potentially advancing treatment options for disorders like psoriasis and atopic dermatitis. © 2026 The Korean Society of Industrial and Engineering Chemistry.