Topical maltotetraose alleviates chronic pruritus by restoring skin barrier function and cutaneous homeostasis in C57BL/6J mice.

Food-grade ingredients are attracting increasing attention in cosmetic applications owing to their safety, biocompatibility, sustainability, and multifunctionality. Although maltotetraose (G4) has been reported to possess moisturizing and potential anti-pruritic properties, systematic in vivo evidence supporting its efficacy against chronic pruritus remains limited. Therefore, this study evaluated the anti-pruritic effects of topical G4 in an acetone-ether-water (AEW)-induced chronic pruritus mouse model and characterized the associated changes in skin barrier function, oxidative stress, inflammatory responses, neural-related signaling, and skin microbiota composition. G4 treatment significantly reduced scratching behavior and dermatitis severity while improving skin hydration and barrier function. These improvements were accompanied by enhanced expression of barrier-related proteins, increased antioxidant enzyme activities, reduced pro-inflammatory cytokine levels, and decreased mast cell degranulation. G4 treatment was also associated with lower expression of itch-related transient receptor potential channels and substance P/neurokinin-1 receptor signaling markers, as well as reduced cutaneous nerve fiber density. Furthermore, 16S rRNA sequencing revealed alterations in skin microbiota composition, including increased relative abundances of potentially beneficial taxa such as Adlercreutzia and Bifidobacterium and decreased abundance of Pseudomonas. Collectively, these findings suggest that G4 alleviates chronic pruritus in association with coordinated improvements in skin barrier function, inflammatory status, neural-related signaling, and microbiota composition, highlighting its potential as a food-derived ingredient for future skin health applications.