The Urogenital Lactobacillus Axis Across Menopause: Connections Between the Vagina, Bladder, and Urinary Metabolome

Alterations in the female urinary microbiome have been linked to several several common urinary conditions that increase in prevalence after menopause. Here we use sequencing and metabolomic data to compare the urinary bladder microenvironments between women who are premenopausal, postmenopausal, and postmenopausal using vaginal estrogen. While the urinary microbiome differs between pre- and postmenopausal women, at least 6 weeks of vaginal estrogen is associated with higher urinary lactobacilli and fewer opportunistic pathogens in the urinary postmenopausal microbiome, which closer approximates what is seen in the premenopausal context. Changes in urinary Lactobacillus species are correlated with vaginal pH and the same Lactobacillus species found in the vaginal microbiome tend to also be identified within the urinary bladder microbiome. Urinary metabolites differ by context (e.g., pre-, post-, and post-menopausal using vaginal estrogen), but the majority of metabolites that drive these differences are unannotated. Of the metabolites with shared associations among different Lactobacillus species, L. iners have consistently inverse relationships compared to L. crispatus, L. gasseri, or L. jensenii.