Table 1_Enterococcus faecium secreted the NlpC/P60 family protein to enhance host immunity and indirectly increases Akkermansia muciniphila for slowing aging.xlsx

While probiotics like Enterococcus faecium are known for gut health benefits, their potential anti-aging effects are poorly understood. This study investigated whether E. faecium fermentation broth delays aging and explored its mechanisms. Using a mouse model, lifespan assays suggested that the E. faecium fermentation broth may contribute to lifespan extension, indicating anti-aging properties. Microbiome analysis showed it modulated gut microbiota, increasing beneficial Akkermansia abundance. Key active components identified included myo-inositol (promoting hair follicle growth), D-ribose, and secreted proteins. While myo-inositol increased the abundance of Lactobacillus reuteri and Lactobacillus johnsonii, it did not increase Akkermansia. A high-content secreted protein, NlpC/P60, present in E. faecium fermentation broth, may enhance host immunity through the NOD-like receptor signaling pathway, thereby restricting pathogen colonization and reshaping the gut microbiota. This immune boost indirectly elevated levels of beneficial bacteria like Akkermansia muciniphila and L. johnsonii, improving overall microbiota composition and mitigating age-related diseases. The findings demonstrate that E. faecium fermentation broth combats aging through multiple pathways, primarily microbiota modulation and immune enhancement. The identification of NlpC/P60 as a key mediator provides crucial mechanistic insight. This study elucidates the material basis and pathways by which E. faecium fermentation broth delays aging, offering experimental support for developing novel microecological therapies against age-related diseases.

尽管诸如屎肠球菌（Enterococcus faecium）这类益生菌以其肠道健康益处为人熟知，但其潜在的抗衰老作用却鲜有研究阐明。本研究旨在探究屎肠球菌发酵液是否具有延缓衰老的功效，并对其作用机制展开探索。通过小鼠模型开展的寿命实验结果显示，屎肠球菌发酵液可延长受试个体寿命，提示其具备抗衰老特性。微生物组分析表明，该发酵液可调节肠道菌群，提升有益菌阿克曼菌（Akkermansia）的丰度。研究鉴定出的关键活性成分包括肌醇（myo-inositol，可促进毛囊生长）、D-核糖以及分泌蛋白。尽管肌醇可提升罗伊氏乳杆菌（Lactobacillus reuteri）与约翰逊乳杆菌（Lactobacillus johnsonii）的丰度，却无法增加阿克曼菌的数量。屎肠球菌发酵液中含量较高的分泌蛋白NlpC/P60，可通过NOD样受体（NOD-like receptor）信号通路增强宿主免疫力，进而抑制病原体定植并重塑肠道菌群结构。该免疫增强作用可间接提升嗜黏蛋白阿克曼菌（Akkermansia muciniphila）与约翰逊乳杆菌等有益菌的水平，优化整体菌群组成并缓解衰老相关疾病。本研究结果证实，屎肠球菌发酵液可通过多重通路发挥抗衰老作用，核心机制为菌群调节与免疫增强。将NlpC/P60鉴定为关键介导因子，为该抗衰老机制提供了重要的理论依据。本研究阐明了屎肠球菌发酵液延缓衰老的物质基础与作用通路，为开发针对衰老相关疾病的新型微生态疗法提供了实验支撑。