The Estrogen Impact on Overactive Bladder Syndrome: Female Pelvic Floor Microbiomes and Antimicrobial Peptides

Overview

The medical field is beginning to adopt treatments that alter an individual's microbiome to improve patient health; however, this approach has not been adopted for treatment of lower urinary tract symptoms (LUTS). Here, the investigators propose the first step in development of such a therapy. If the investigators hypothesis is correct, the investigators could change the first line of treatment for hypoestrogenic women and develop future therapies that modulate bacteria in the bladder to improve not only LUTS but also treatment response. This could lead to the first treatment for lower urinary disorders that incorporates a person's individual microbiome.

Overactive bladder (OAB) syndrome is characterized by the symptom complex of urinary urgency, usually with associated frequency and nocturia, with or without urgency urinary incontinence in the absence of infection or other pathology. Vaginal estrogen, a well-documented treatment for OAB in hypoestrogenic women, has been shown to improve symptoms of frequency, urgency and urgency urinary incontinence (UUI). Several theories have been proposed to explain the mechanism underlying estrogen's effect on lower urinary tract symptoms (LUTS). Investigators propose that estrogen treatment influences bacterial communities (microbiomes) in the vagina and bladder and alters urothelial and vaginal (AMPs); thereby improving OAB symptoms in hypoestrogenic women. Long-standing medical dogma has been replaced by clear evidence that a female urinary microbiome (FUM) exists.This suggests that the FUM is a factor in lower urinary tract symptoms (LUTS) and that FUM diversity contributes to LUTS and treatment response, like the vaginal microbiome and its contribution to vaginal symptoms. In hypoestrogenic women, the vaginal microbiome shifts from low diversity communities, commonly dominated by Lactobacillus, to more diverse communities dominated by anaerobes; this change can be reversed with estrogen treatment. Since the FUM of women with OAB includes bacteria similar to those of the vaginal microbiome (e.g. Lactobacillus, Gardnerella, and diverse anaerobes), investigators reason the FUM would respond similarly to estrogen and become less diverse. While almost nothing is known about urinary/vaginal microbiome interplay, even less is known about immune response modulation in the bladder and vagina. However, estrogen reduces the subsequent urinary tract infection (UTI) rate in hypoestrogenic women affected by recurrent UTI, and estrogen induces urothelial antimicrobial peptide (AMP) expression. Since AMPs exhibit microbicidal activity, stimulate inflammation, and facilitate epithelial barrier homeostasis, estrogen may work through AMPs as mediators to optimize microbial equilibrium.