Age-Related Changes, Influencing Factors, and Crosstalk Between Vaginal and Gut Microbiota: A Cross-Sectional Comparative Study of Pre- and Postmenopausal Women.

Objective: The ideal vaginal environment is maintained by Lactobacillus species, which keep the vagina clean and free of infections, boost fertility and immunity. Age-related decline in estrogen affects Lactobacillus population, leading to dominance of nonoptimal species and increased diversity in vaginal microbiota. In this study, we compared the differences between the vaginal microbiota of pre- and postmenopausal women. We also examined the relationships between vaginal and gut microbiota, their relationships with sex hormones and equol-producing ability. Materials and Methods: This was a cross-sectional study of 35 premenopausal and 35 postmenopausal women (age range: 27-76 years). We compared parameters such as the composition of the gut and vaginal microbiota, vaginal pH, estradiol, follicular stimulating hormone, and urinary equol concentration. Results: In the vaginal microbiota of premenopausal women, Lactobacillus species constituted ∼71.98%, and nonoptimal species constituted ∼16.87%. They were 10.08% and 26.78%, respectively, in the vaginal microbiota of postmenopausal women. The proportion of Lactobacillus was significantly low, whereas microbial diversity and vaginal pH were significantly high (p < 0.0001) in postmenopausal women. The compositions of the vaginal microbiota were significantly different in pre- and postmenopausal women. However, such differences were not noticeable in the gut microbiota. Urinary equol production had no significant correlation with vaginal microbiota, although it had significant relationships with gut microbiota in postmenopausal women. In both groups, the proportions of vaginal Lactobacillus were inversely correlated with vaginal microbial diversity and vaginal pH. Conclusion: Postmenopausal women had significantly low Lactobacillus and high nonoptimal species in their vaginal flora, whereas such age-related differences were not identified in gut microbiota. Urinary equol concentration had significant correlation with gut microbiota in postmenopausal women only. This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (Trial registration No.: UMIN000043944).

Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial.

As estrogen level decreases with aging, the vaginal mucosa gets thinner, and collagen amount decreases. In addition, the population of Lactobacillus in the vagina declines, increasing the risk of atrophic vaginitis, bacterial vaginosis, and genitourinary symptoms in the postmenopausal women. In this study, we evaluated the effects of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women. This was a pilot randomized controlled trial in 35 premenopausal and 35 postmenopausal healthy women. For 4 weeks, treatment 1 group (14 premenopausal and 16 postmenopausal women) used the Lactobacillus-containing feminine soap and cream, and treatment 2 group (15 premenopausal and 14 postmenopausal women) used Lactobacillus-containing feminine gel in addition to soap and cream. The remaining 6 premenopausal and 5 postmenopausal women served as controls without using any products. We then compared the changes in the vaginal microbiota, genitourinary symptoms, and other related biomarkers after completion of treatment. Vaginal pH and pathogenic flora were reduced in both treatment groups compared to control group, which was more significant in the treatment 2 group of postmenopausal women. Genitourinary symptoms significantly improved in 60% of premenopausal women in treatment 1 group and 81.3% of postmenopausal women in treatment 2 group, compared to control group (0%, p = 0.043 and p<0.01 respectively). Overactive bladder symptom scores were significantly improved after using the products in eleven out of twelve postmenopausal women suspected of having overactive bladder. The use of Lactobacillus-containing feminine products was associated with improved vaginal ecosystem and urogenital health compared to control group, especially in those women using feminine gel.

MiR-21 is enriched in the RNA-induced silencing complex and targets COL4A1 in human granulosa cell lines.

MicroRNAs (miRNAs) are noncoding small RNAs that play important roles in a variety of physiological and pathological events. In this study, we performed large-scale profiling of EIF2C2-bound miRNAs in 3 human granulosa-derived cell lines (ie, KGN, HSOGT, and GC1a) by high-throughput sequencing and found that miR-21 accounted for more than 80% of EIF2C2-bound miRNAs, suggesting that it was enriched in the RNA-induced silencing complex (RISC) and played a functional role in human granulosa cell (GC) lines. We also found high expression levels of miR-21 in primary human GCs. Assuming that miR-21 target mRNAs are enriched in RISC, we performed cDNA cloning of EIF2C2-bound mRNAs in KGN cells. We identified COL4A1 mRNA as a miR-21 target in the GC lines. These data suggest that miR-21 is involved in the regulation of the synthesis of COL4A1, a component of the basement membrane surrounding the GC layer and granulosa-embedded extracellular structure.