Translocation of vaginal microbiota is involved in impairment and protection of uterine health

Abstract

The vaginal and uterine microbiota play important roles in the health of the female reproductive system. However, the interactions among the microbes in these two niches and their effects on uterine health remain unclear. Here we profile the vaginal and uterine microbial samples of 145 women, and combine with deep mining of public data and animal experiments to characterize the microbial translocation in the female reproductive tract and its role in modulating uterine health. Synchronous variation and increasing convergence of the uterine and vaginal microbiome with advancing age are shown. We also find that transplanting certain strains of vaginal bacteria into the vagina of rats induces or reduces endometritis-like symptoms, and verify the damaging or protective effects of certain vaginal bacteria on endometrium. This study clarifies the interdependent relationship of vaginal bacterial translocation with uterine microecology and endometrial health, which will undoubtedly increase our understanding of female reproductive health.

The Endometrial Microbiome and Its Impact on Human Conception

“…There are significant fluctuations in bacterial communities in the FGT. These shifts correlate with parameters such as age, hormonal changes, ethnicity, and intrauterine devices [ 9 , 17 , 19 , 25 , 27 ]. Although most data come from vaginal samples given the site’s easy accessibility and lower risk of sample contamination, there is increasing knowledge about changes in the endometrial microbiome.…”

“…Furthermore, there is a significant impact of age in bacterial communities inside the uterus. Microbial diversity within samples (alpha diversity) decreases with advancing age, while interindividual similarity (beta diversity) is higher among women ages 20 years and younger, suggesting that dissimilarities among patients accumulate with age [ 25 ]. Older age, number of abortions, and vaginal delivery may reduce the differences between endometrial and vaginal microbiomes via perturbation of the closed uterine environment through cervical incompetence, which ultimately suggests that alterations in the vaginal microbiome could directly affect bacterial communities in the endometrium in certain circumstances [ 25 ].…”

“…Microbial diversity within samples (alpha diversity) decreases with advancing age, while interindividual similarity (beta diversity) is higher among women ages 20 years and younger, suggesting that dissimilarities among patients accumulate with age [ 25 ]. Older age, number of abortions, and vaginal delivery may reduce the differences between endometrial and vaginal microbiomes via perturbation of the closed uterine environment through cervical incompetence, which ultimately suggests that alterations in the vaginal microbiome could directly affect bacterial communities in the endometrium in certain circumstances [ 25 ]. This theory is corroborated by findings that the majority of patients with an NLD endometrial microbiota also had an NLD vaginal microbiota, and all patients with dysbiotic vaginal communities had an NLD endometrial status [ 16 ].…”

“…The sample cohort is one of the biggest limitations on endometrial microbiome studies. Patient characteristics—such as ethnicity, age, and sexual habits—should be carefully considered during the process of cohort selection, as several studies have suggested that these characteristics may be responsible for community fluctuations in the FGT, including the uterus [ 19 , 25 , 28 ]. For instance, important taxa dissimilarities were observed between patients of different genetic backgrounds, suggesting that black women harbor a distinct FGT microbiome [ 19 , 99 , 100 ].…”

“…In another study, there was great dissimilarity among endometrial samples from 10 patients undergoing hysterectomy, with Acinetobacter , Corynebacterium , Lactobacillus , and Staphylococcus detected in variable abundances [ 24 ]. Of note, the study included premenopausal, perimenopausal, and postmenopausal patients, a design that could greatly impact results and study comparison because of the natural changes occurring in microbiota across the lifespan [ 25 ]. Interestingly, endometrial microbiota from 34 women of European descent undergoing ART treatment showed six possible biomarker species for the endometrium—namely Kocuria dechangensis , Sphingomonas paucimobilis , Stenotrophomonas maltophilia , Agrobacterium tumefaciens , Delftia tsuruhatensis , and Cutibacterium acnes —together with an almost total absence of Lactobacillus [ 26 ].…”