Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation

作者：Aurélien Trompette, Julie Pernot, Olaf Perdijk, Rayed Ali A. Alqahtani, Jaime Santo Domingo, Dolores Camacho‐Muñoz, Nicholas C. Wong, Alexandra C. Kendall, Andreas Wiederkehr, Laurent Pierre Nicod, Anna Nicolaou, Christophe von Garnier, Niki D. J. Ubags, Benjamin J. Marsland · 发表于：Mucosal Immunology · 年份：2022 · DOI：10.1038/s41385-022-00524-9 · 被引用次数：228 · 研究领域：Dermatology and Skin Diseases、Asthma and respiratory diseases、Exercise and Physiological Responses

Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.The Graphical Abstract was designed using Servier Medical Art images ( https://smart.servier.com ).