Abstract
BACKGROUND: Wound healing is a complex physiological process essential for restoring tissue integrity following various injuries, ranging from minor, everyday incidents to post-surgical complications. Emerging studies have demonstrated that lactic acid bacteria (LAB) can offer benefits beyond gut health, extending their positive effects on skin health. This study investigated the potential of Lactobacillus reuteri NCHBL-005, a honeybee-derived probiotic strain, to enhance fibroblast-mediated wound healing. METHOD: L929 cells and mouse embryonic fibroblasts (MEFs) were utilized as models to specifically target fibroblasts. To assess the wound healing potential in vitro, a scratch assay was performed, providing insights into wound closure. Additionally, we created wound models in mice to evaluate the in vivo effects of the treatment. RESULTS: Our results showed that L. reuteri NCHBL-005 significantly accelerated wound closure in L929 fibroblast compared to other lactobacilli and exhibited superior efficacy in activating the mitogen-activated protein kinase (MAPK) pathway. Through MAPK inhibition assays, we confirmed that the wound healing effects of L. reuteri NCHBL-005 were MAPK-dependent, promoting fibroblast proliferation and differentiation. Notably, L. reuteri NCHBL-005 treatment did not facilitate wound healing in MEF cells derived from Toll-like-receptor 2 knockout (TLR2(-/-)) mice, highlighting the critical role of TLR2 in this mechanism. In vivo studies further corroborated these findings, in which topical administration of L. reuteri NCHBL-005 enhanced wound healing and stimulated fibroblast proliferation and activation, as confirmed by histopathological analysis. CONCLUSION: These findings revealed that L. reuteri NCHBL-005 activates fibroblasts through TLR2 stimulation and subsequent MAPK pathway activation, suggesting its potential as a promising therapeutic candidate for wound management.