Abstract:[Objective] This study aims to explore the role of Lactobacillus in enhancing host immunocompetence and preventing vaginal infections with Candida albicans. [Method] A human vaginal epithelial cell (VK2/E6E7 cell) model was employed to screen the most potent strain among ten vaginal Lactobacillus isolates in inducing the antimicrobial peptide LL-37. A mouse model of vaginal infection with Candida albicans was established. The effects of oral administration of the selected Lactobacillus strain on vaginal mucosal immunity, systemic inflammatory balance, and vaginal microbiota homeostasis were systematically evaluated using hematoxylin-eosin (HE) staining, ELISA, qPCR, and 16S rRNA sequencing. [Result] Both the cell lysate and fermentation supernatant of Lacticaseibacillus paracasei CCFM1433 upregulated antimicrobial peptide LL-37 secretion in VK2/E6E7 cells by 22.5% and 12.3%, respectively, compared with the control group, exhibiting superior activity over those of other strains. Live Lacticaseibacillus paracasei CCFM1433 increased the level of cathelicidin-related antimicrobial peptide (CRAMP) in the vaginal tissue to 1.82 times that of the model group, increased the level of secretory immunoglobulin A (sIgA) by 52.9%, and the level of immunoglobulin G (IgG) in the serum by 16.9% compared with the model group. It also increased the level of IL-10 in the spleen by 23.9%, while reducing the TNF-α level by 20.3%. In addition, both live Lacticaseibacillus paracasei CCFM1433 and its postbiotics inhibited the TLR4/MyD88 signaling pathway, preventing overactivation of inflammatory pathways. The 16S rRNA sequencing results indicated that the live bacteria of this strain effectively maintained the vaginal homeostasis of Lactobacillus communities and its intervention effect was closely associated with a significant enrichment of functional genes in the signaling molecules and interaction pathway in the mouse vaginal microbiome. [Conclusion] Lacticaseibacillus paracasei CCFM1433 exerts an anti-infection effect and effectively prevents Candida albicans infections by directly activating host mucosal immunity, modulating inflammatory responses, and restoring the Lactobacillus-dominant vaginal microbiota. These findings provide theoretical support for the application of probiotics in preventing vaginal infections.
