植物乳植杆菌CCFM1352发酵代谢产物对毛囊周期的作用及机制探讨

Effects and mechanistic insights of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites on hair follicle cycling

摘要:

目的 针对脱发治疗维持性差、长期用药受限等问题，本研究利用体外人真皮乳头细胞(human dermal papilla cells, HDPCs)模型和休止期C57BL/6小鼠模型，研究植物乳植杆菌(Lactiplantibacillus plantarum) CCFM1352发酵代谢产物及菌体组分对毛囊周期的调控作用及相关机制。方法 体外以不同浓度的CCFM1352发酵代谢产物或菌体裂解物处理HDPCs，检测细胞活力及Wnt/β-catenin、生长期与退行期转换、细胞凋亡相关分子的表达水平；体内于休止期C57BL/6小鼠连续口服发酵代谢产物或灭活菌体21 d，评估毛发覆盖率、毛囊形态结构及相关信号分子的变化。结果 体积分数为10%的CCFM1352发酵代谢产物可将HDPCs活力提升至135.30%，并上调Wnt10b、FGF-7表达，下调DKK1、TGF-β1表达，同时伴随Bcl-2上调与Bax下调，整体呈现有利于毛囊生长期的分子信号变化。体内实验表明，连续口服CCFM1352发酵代谢产物可促进毛囊由休止期向生长期转变，毛发覆盖率提高至61.62%，毛囊密度和真皮厚度显著增加，同时增强β-catenin积累及核转位。相比之下，菌体组分在体内外模型中的调控作用整体较弱，仅在部分指标上表现出有限改善。结论 CCFM1352发酵代谢产物可通过调节Wnt/β-catenin信号通路相关分子，以及FGF-7、TGF-β1、Bcl-2、Bax等关键因子的表达促进毛囊由休止期向生长期转变，在毛发健康维护方面具有潜在应用价值。本研究为益生菌来源生物活性代谢产物在毛发健康领域的开发利用提供了实验依据。

Abstract:

Objective To address the limitations of current hair-loss treatments, we employed an in vitro human dermal papilla cell (HDPC) model and a telogen C57BL/6 mouse model to study the effects of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites and bacterial preparations on the hair follicle cycle and decipher the associated molecular mechanisms.Methods HDPCs were treated with different concentrations of CCFM1352 fermentation metabolites or bacterial lysates in vitro, and cell viability as well as the expression of molecules related to Wnt/β-catenin signaling, anagen/catagen regulation, and apoptosis was assessed. Telogen C57BL/6 mice were administrated with the fermentation metabolites or heat-killed bacterial cells by gavage for 21 days, and changes in hair coverage, follicular structure, and associated signaling molecules were analyzed.Results CCFM1352 fermentation metabolites at a volume fraction of 10% increased the viability of HDPCs to 135.30%, up-regulated Wnt10b and FGF-7, down-regulated DKK1 and TGF-β1, and increased Bcl-2 and decreased Bax, inducing a favorable change pattern associated with the anagen phase. Continuous gavage of the fermentation metabolites promoted the transition of hair follicles from telogen to anagen, increased the hair coverage to 61.62%, and enhanced hair follicle density, dermal thickness, and β-catenin accumulation and nuclear translocation. However, the regulatory effects of bacterial lysate and heat-killed bacteria were weaker in both models and showed only limited improvements in some indices.Conclusion CCFM1352 fermentation metabolites could modulate Wnt/β-catenin-related molecules and the expression of key factors such as FGF-7, TGF-β1, Bcl-2, and Bax, which favors the transition of hair follicles from telogen to anagen and suggests an important role in promoting hair growth. This study provides experimental evidence for the application of bioactive metabolites from probiotics in the field of hair health.