Enterococcus faecium secreted the NlpC/P60 family protein to enhance host immunity and indirectly increases Akkermansia muciniphila for slowing aging

While probiotics like <i>Enterococcus faecium</i> are known for gut health benefits, their potential anti-aging effects are poorly understood. This study investigated whether <i>E. faecium</i> fermentation broth delays aging and explored its mechanisms. Using a mouse model, lifespan assays suggested that the <i>E. faecium fermentation</i> broth may contribute to lifespan extension, indicating anti-aging properties. Microbiome analysis showed it modulated gut microbiota, increasing beneficial <i>Akkermansia</i> abundance. Key active components identified included myo-inositol (promoting hair follicle growth), D-ribose, and secreted proteins. While myo-inositol increased the abundance of <i>Lactobacillus reuteri</i> and <i>Lactobacillus johnsonii</i>, it did not increase <i>Akkermansia</i>. A high-content secreted protein, NlpC/P60, present in <i>E. faecium</i> 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 <i>Akkermansia muciniphila</i> and <i>L. johnsonii</i>, improving overall microbiota composition and mitigating age-related diseases. The findings demonstrate that <i>E. faecium</i> 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 <i>E. faecium</i> fermentation broth delays aging, offering experimental support for developing novel microecological therapies against age-related diseases.