From Reshaped Metabolome to Repaired Skin: Fermented Gastrodia elata Alleviates UVB-Induced Damage Through Controlled Immune Activation

UVB radiation induces cutaneous damage through oxidative stress and immune dysregulation. This study investigated the therapeutic potential of <i>Gastrodia elata</i> fermented by <i>Lactobacillus salivarius</i> AACE1 (GL) in a mouse model of UVB-induced skin injury. Results demonstrated that GL treatment significantly improved skin morphology, enhanced antioxidant activities (SOD and GSH), reduced oxidative damage (MDA), and balanced inflammatory mediators by upregulating TGF-β and IL-10 while downregulating TNF-α, IL-6, and IL-1β. Transcriptomic analysis revealed that GL specifically activated NOD-like receptor signaling pathway components (<i>Nlrp3</i>, <i>Casp4</i>, and <i>Gbp2/5</i>) while inducing <i>Tnfaip3</i> to establish negative feedback control. Metabolomic profiling confirmed that fermentation transformed the metabolite landscape, enriching collagen-related dipeptides, antimicrobial/anti-inflammatory metabolites, and antioxidant cofactors. Importantly, comparative analysis showed that GL is more effective than vitamin E in coordinating multiple signaling pathways and maintaining inflammatory homeostasis. These findings establish GL as an effective natural product that alleviates UVB-induced skin damage through synchronized metabolic remodeling and controlled immune activation.