Vaginal-Derived Potential Probiotics and Their Postbiotics Alleviate Aerobic Vaginitis via Suppressing TLR4/MyD88/NF-κB Signalling Pathway and Potentially Enhancing Vaginal Barrier.

Abstract

Antibiotic therapy is currently challenged by drug resistance and high recurrence in aerobic vaginitis (AV), making it urgent to seek novel strategies. In this study, we selected two potential probiotic strains Lactobacillus crispatus YBR-01 (L. crispatus YBR-01) and Lactiplantibacillus plantarum YBR-01 (L. plantarum YBR-01) from our proprietary bacterial library, and comprehensively evaluated the protective potential against AV in mouse model induced by a pathogen cocktail. Supplementation with L. crispatus YBR-01 and L. plantarum YBR-01, either individually or in combination, attenuated vaginal edema, reduced proinflammatory mediators, and restored anti-inflammatory cytokines, with the combination therapy yielding the best results. Mechanistically, the combination of strains significantly inhibited the TLR4/MyD88/NF-&#x3ba;B cascade (p&#x2009;<&#x2009;0.05), restored vaginal mucosal integrity (p&#x2009;<&#x2009;0.01), and rebalanced the Th17/Treg immunity (p&#x2009;<&#x2009;0.05). Moreover, given that postbiotics represent a safe and highly stable alternative strategy with emerging translational potential, the research investigated their impact derived from L. crispatus YBR-01 and L. plantarum YBR-01 on the phenotypic characteristics and molecular profile of the AV mouse model. While postbiotics could synergistically alleviate the AV-like murine phenotype and improve inflammatory markers, the impacts were quantitatively similar as those observed with the live strain combination (p&#x2009;<&#x2009;0.05). More importantly, the postbiotics effectively mirrored the mechanisms of their live counterparts by downregulating the TLR4/MyD88/NF-&#x3ba;B pathway (p&#x2009;<&#x2009;0.01), demonstrating the potential to enhance vaginal barrier (p&#x2009;<&#x2009;0.01) and restoring Th17/Treg balance (p&#x2009;<&#x2009;0.05), with the combination of postbiotics exhibiting superior advantages over monotherapy. Our study unveiled the therapeutic benefits of both potential probiotic Lactobacillus spp. and their postbiotics in AV, presenting an ideal prospect for clinical translation.