The vaginal microbiome is critical for the reproductive health of women, yet the differential impacts exerted by the host and by ambient environmental variables on the vaginal microbiome remain largely unknown. Here, we conducted a comprehensive cross-sectional study of the relationships between the vaginal microbiome and 81 matched host and environmental variables across 6755 Chinese women. By 16S rRNA sequencing, we identified four core vaginal microbiota with a prevalence of over 90% and a total median abundance of 98.8%. Twenty-four variables, including physiology, lifestyle behaviors, gynecologic history, social and environmental information, were found associated with the microbiome composition, of which bacterial vaginosis (BV) showed the largest effect size. Age was among the strongest explanatory variables and the vaginal microbiome dynamically succeeded with increasing age, especially with a composition turning point at the age of 45. Our mediation analyses indicated that the effects of age on the microbiome could be mediated by variables such as parity number and lifestyles. We further classified the vaginal microbiomes of the population into 13 "Vagitypes". Women with Lactobacillus iners- and Lactobacillus jensenii-dominated Vagitypes had significantly higher live birth rate than those with Vagitype dominated by Fannyhessea vaginae (53.40%, 59.09% vs 21.43%
OR [95% CI]: 3.62 [1.12-14.87], 5.39 [1.27-27.36]
P = 0.031, P = 0.021). This study provides a comprehensive overview of the associations between identified variables and the vaginal microbiome, representing an important step toward understanding of environment-microbe-host interactions.