Association Between Vaginal Commensal Microbiota And Health Of Reproductive Tract In Postmenopausal Women

Atrophic vaginitis is defined as inflammation of the vaginal epithelium due to atrophy secondary to decreased levels of circulating estrogen,and it is a common finding among 25% to 50% of postmenopausal women.The preferred treatment to date has been based on estrogen therapy after a thorough assessment of its risks and benefits.Nevertheless,long-term estrogen-replacement therapy still mines some risks and impacts that have been noticed and discussed for decades.With the dramatic progresses in Human Microbiome Project(HMP)and molecular microecological technology,major efforts are currently under way to better understand the vaginal microbiota,whereas the potential role of commensal bacteria playing sustaining vaginal health has been continuously concerned.In spite of the current understanding of pathogenesis and treatment in atrophic vaginitis,little is known about the composition and structure of vaginal bacterial community in postmenopausal women and much less about its etiological role playing in atrophic vaginitis.And to date,there is no research in this field by molecular microecological method in China.Here,we firstly identified the composition,distribution as well as dynamics of vaginal bacterial communities in 29 healthy postmenopausal women over a 4-week period by classifying 16 S r RNA gene sequences in each sample using next-generation deep sequencing(Illumina sequencing).The results derived from the study demonstrated that Lactobacillus was generally the most prevalent and abundant species in healthy participants and predominately drove the main functions with constituting the main body of vaginal community,which countered the long-held view that lactobacilli are absent or depleted in menopause.The communities in healthy women commonly remained fairly steady due to the innate situations after menopause,and prevented the collapse of the vaginal ecosystem.Secondly,we analyzed and compared the profiles of vaginal bacterial communities in postmenopausal women with or without atrophic vaginitis,revealed the changes during estrogen treatment and screened the risk/benefit strains by deep transcription of metadata.Our finding indicated that differences of vaginal microbiota were detected between patients and healthy women(p<0.05),and at the end of medication,the communities in patients became similar to those in asymptomatic participants along with the improvement of clinical characteristics.Moreover,Lactobacillus was negative correlated(p<0.0001)with symptom score,whereas Gardnerella and Atopobium were positively correlations with genital symptom(p<0.001 and p<0.05,respectively).Thirdly,to investigate host-vaginal microbiota interactions and the impact on immune barrier function,we colonized human vaginal epithelial cells in vitro model with Atopobium vaginae and Lactobacillus crispatus in different MOI with/without estrogen cultivation.ELISA was used for assessing the levels of pre-inflammation cytokines and chemokines in supernatant.We observed that vaginal epithelial cells secreted IL-6 and IL-8 in bacterial-amount-dependent response to Atopobium vaginae,but not to Lactobacillus crispatus.When cultured in estrogen environment,the innate response of vaginal epithelial cells triggered by Atopobium vaginae was compromised and suppressed.In conclusion,in most women after menopause,a lactobacilli-dominating vaginal microbiota still kept playing its benefit role in health maintenance,while the community dynamics remained relatively steady over a short period of time.The alternations of vaginal bacterial community composition and structure were strongly relevant to the host's dynamic shift between health and risk to atrophic vaginitis,especially the changes in relative abundance of Lactobacillus spp.,Gardnerella and Atopobium by which the vaginal epithelial cells were triggered an abnormal secretion of IL-6 and IL-8.When treated with estrogen,there was a dramatic response of bacteria communities and then a lactobacilli-dominated vaginal microbiota restored.The innate immune response of vaginal epithelial cells induced by Atopobium was beneficially modulated by estrogen,while the community diversity dropped and contributed to raising a more stable vaginal ecosystem with strong resistance/resilience capacity to maintain delicate balance and stay healthy.