Protective effects of probiotics against menopausal symptoms in ovariectomized mice

With growing interest in the role of the gut microbiome in the pathogenesis of menopausal disorders, probiotic supplementation is emerging as a novel therapeutic strategy for postmenopausal women. In this study, we investigated the protective effects of several probiotic strains against menopausal symptoms using an ovariectomized (OVX) mouse model fed a high-fat diet, in comparison with the effects of 17β-estradiol (E2) replacement. Among the eight tested probiotic strains, we selected four (Limosilactobacillus fermentum MG901, Lactiplantibacillus plantarum MG4604, Ligilactobacillus salivarius MG4679, and Lacticaseibacillus reuteri MG5463) that showed superior estrogen-like activity in an uterotrophic assay. We then examined their effects in OVX mice. The probiotic MG4679 was tested in combination with MG5463. During the 12-week experimental period, oral administration of the four probiotics reduced blood glucose and body temperature and ameliorated depression-like behavior in OVX mice. In the Barnes maze test, MG901 and MG4604 improved the spatial memory deficits observed in OVX mice. Micro-CT analysis of mouse femurs revealed that MG5463 prevented the OVX-induced reduction in cortical bone mineral density and bone volume fraction. Importantly, similar to E2 replacement, most of the test probiotics increased Akt phosphorylation in skeletal muscle, estrogen receptor-α (ER-α) protein expression in the liver, and ERK phosphorylation in the brain of OVX mice. However, unlike E2 treatment, all probiotics did not affect uterine weight, uterine ER-α expression, and serum E2 concentration. These results indicated that the probiotics used in this study exhibited protective effects against menopausal symptoms, partly through estrogen-mimetic action, without unfavorable uterine stimulation in OVX mice.