Context-Dependent Short-Chain Fatty Acids in Inflammatory Skin Diseases: Immunometabolic Mechanisms, Evidence Boundaries, and Translational Perspectives - PubMed
4 hours ago
- #inflammatory skin diseases
- #short-chain fatty acids
- #gut-skin axis
- Short-chain fatty acids (SCFAs) have anti-inflammatory and barrier-regulatory potential but their effects are context-dependent and not uniformly beneficial.
- SCFAs like acetate, propionate, and butyrate regulate cutaneous immunity and barrier function through various mechanisms including FFARs, HCAR2, HDAC inhibition, and metabolic-substrate effects.
- Outcomes of SCFAs depend on factors such as species, source, dose, tissue bioavailability, pH, receptor expression, target-cell identity, and disease stage.
- Gut-derived SCFAs support systemic immunometabolic regulation and barrier maturation, while local cutaneous SCFAs can maintain homeostasis or amplify inflammation in pilosebaceous niches.
- SCFA mechanisms are discussed across various cell types including immune cells, keratinocytes, sebocytes, fibroblasts, adipocytes, and endothelial cells.
- The review interprets SCFA relevance to multiple inflammatory skin diseases like atopic dermatitis, psoriasis, acne vulgaris, rosacea, hidradenitis suppurativa, chronic spontaneous urticaria, and contact dermatitis.
- Strategies for SCFA application include dietary, prebiotic/probiotic, topical, fecal microbiota transplantation, engineered probiotic, prodrug, and delivery-based approaches, distinguishing SCFA-specific causality from microbiome remodeling.
- A context-resolved framework is needed to translate SCFA biology into rational immunometabolic interventions for inflammatory skin diseases.