Lactobacillus gasseri postbiotics ameliorate age-related decline in endometrial receptivity.

Endometrial senescence contributes to a decline in fertility in women of advanced reproductive age, with emerging evidence linking it to remodeling of the uterine microbiome, particularly a reduced Lactobacillus abundance. Here, using a cross-sectional human cohort with clinical follow-up, we identify an age-related shift in the endometrial microbiome, characterized by the loss of beneficial Lactobacillus-enriched states and increased Lactobacillus iners. This shift is associated with impaired endometrial receptivity and less favorable embryo transfer outcomes. Functional screening of reproductive tract isolates highlights Lactobacillus gasseri as a candidate strain with strong antioxidant, anti-inflammatory, and adhesion-related activities. In cells and mouse models, L. gasseri and its exopolysaccharides (EPSs) attenuate endometrial senescence and improve implantation in aged mice. Mechanistically, these effects are mediated, at least partly, through the modulation of Hippo-YAP signaling. These findings suggest that restoring beneficial Lactobacillus and applying EPSs may represent complementary strategies to improve endometrial function and fertility outcomes in women of advanced reproductive age.