Lactobacillus crispatus-derived nCEV vesicles promote cutaneous wound healing and inhibit HPV16 infection.

UNLABELLED: Cervical cancer (CC) is a common gynecological malignancy, primarily associated with persistent infection by high-risk human papillomavirus (HPV). The vaginal microbiota, dominated by Lactobacillus species, plays a critical role in maintaining a healthy vaginocervical microenvironment. However, the influence of Lactobacillus on the pathogenesis and treatment of CC remains underexplored. Here, we report that the optimized 60-80 nm size dominant of extracellular vesicles from various Lactobacillus species (nLEVs) significantly affects cutaneous wound healing and HPV infection. Specifically, nCEVs from Lactobacillus crispatus demonstrate superior efficacy compared to nIEVs from Lactobacillus iners in promoting cell migration, angiogenesis, and wound healing via macrophage M2 polarization and blocking intravaginal HPV16 infection. Moreover, metabolic profiling revealed that D-lactate may be key to the functions of nCEVs. Altogether, our findings uncover a novel nCEV/D-lactate-mediated mechanism that promotes homeostasis and offers potential new approaches for the prevention and treatment of CC.

IMPORTANCE: This study identifies Lactobacillus crispatus-derived vesicles (nCEVs) as crucial for cervicovaginal homeostasis, functioning through promoting wound healing via macrophage polarization and blocking HPV infection, and delivering D-lactate-a key bioactive component. These insights advance microbiome-based female healthcare interventions.