Qingying Shi, Fanglu Yu, Maoyuan Zhou, Hongmin Niu, Hong Zhao, Mohan Xu, Linbang Long, Zhepeng Cao, Xinyue Yu, Yanxiang Jiang, Fufeng Liu, Fuping Lu, Zhengmei Huang, Xihong He, Huabing Zhao
In vitro, L. plantarum EVs were efficiently internalized by HaCaT keratinocytes, significantly increasing ceramide levels and upregulating key barrier-related genes, including filaggrin (FLG), desmoglein-1 (DSG1), and ceramide synthase 3 (CerS3), thereby enhancing skin barrier function in the AD-like cell model. Meanwhile, EVs treatment downregulated pro-inflammatory cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), interleukin-33 (IL-33), and tumor necrosis factor-α (TNF-α). In the DNFB-induced AD mouse model, EVs administration markedly alleviated clinical symptoms, reduced lesion scores and transepidermal water loss, and restored epidermal thickness to near-normal levels, indicating barrier repair in AD mice. Skin tissue analysis further confirmed reduced inflammatory cytokine expression. Additionally, EVs suppressed scratching behaviors by inhibiting the IL-31 pathway. Multi-omics analysis suggested that the therapeutic effects of L. plantarum EVs may be associated with lipid-based bioactive components within EVs.
INTRODUCTION: Atopic dermatitis (AD), a chronic inflammatory skin disorder, represents a significant global health challenge. Although probiotic therapy shows potential for skin disease management, the application of live bacteria remains associated with multiple limitations. Bacterial extracellular vesicles (EVs) may provide a safer and more effective alternative.
METHODS: In this study, EVs derived from Lactobacillus plantarum were isolated and characterized. Their therapeutic potential against AD was evaluated through in vitro and in vivo experiments. HaCaT keratinocytes were used to establish an AD-like cellular model, and an AD mouse model was induced using 2,4-dinitrofluorobenzene (DNFB). The effects of L. plantarum EVs on skin barrier function, inflammatory responses, and scratching behaviors were evaluated. Multi-omics analysis was performed to explore the potential bioactive components within EVs underlying their therapeutic effects.
RESULTS: In vitro, L. plantarum EVs were efficiently internalized by HaCaT keratinocytes, significantly increasing ceramide levels and upregulating key barrier-related genes, including filaggrin (FLG), desmoglein-1 (DSG1), and ceramide synthase 3 (CerS3), thereby enhancing skin barrier function in the AD-like cell model. Meanwhile, EVs treatment downregulated pro-inflammatory cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), interleukin-33 (IL-33), and tumor necrosis factor-α (TNF-α). In the DNFB-induced AD mouse model, EVs administration markedly alleviated clinical symptoms, reduced lesion scores and transepidermal water loss, and restored epidermal thickness to near-normal levels, indicating barrier repair in AD mice. Skin tissue analysis further confirmed reduced inflammatory cytokine expression. Additionally, EVs suppressed scratching behaviors by inhibiting the IL-31 pathway. Multi-omics analysis suggested that the therapeutic effects of L. plantarum EVs may be associated with lipid-based bioactive components within EVs.
DISCUSSION: These findings indicate that bacterial EVs represent a promising probiotic-inspired strategy for AD treatment and provide new insights into the development of safe and effective dermatological therapies.