# Defining the dynamics of urobiome structure and function in postmenopausal women and its role in recurrent UTI susceptibility

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2022 · $64,925

## Abstract

Community-acquired urinary tract infection (UTI) is among the most common bacterial infections worldwide,
affecting at least 150 million people annually. When a patient suffers 3 UTIs within a 12-month period, the
infection is termed recurrent UTI (rUTI). rUTI severely diminishes quality of life and has become one of the most
difficult urologic diseases to manage in women. Rates of range from 19-36% in premenopausal women and
increasing to 50% in postmenopausal (PM) women. The higher incidence of rUTI in PM women compared to
premenopausal women suggests that the host environment plays a role in rUTI susceptibility. rUTI management
relies on antibiotic therapy but many front-line antibiotics have become ineffective due to widespread
antimicrobial resistance. To combat the increasing rates of antibiotic-refractory rUTI, new therapies must be
developed. A promising source of new rUTI therapies is the urinary microbiome, termed here the urobiome,
which has been recently identified as an important component of the urinary environment. A critical step in the
development of probiotic therapies is defining niche colonization and maintenance requirements. However, to
date, urobiome studies have been largely focused on compositional classification and have not identified nichespecific urobiome functions or metabolic requirements. Furthermore, the effect of rUTI and the hormonal
changes on urobiome composition and function has not been assessed in PM women.
 We have completed shotgun metagenomic sequencing (MGS) of urine from a cross-sectional cohort of PM
women. In this work we have discovered that urinary lactobacilli (Lb) abundance in women without rUTI was
associated with specific modalities of estrogen hormone therapy (EHT). Our functional analysis of the MGS data
revealed differential enrichment in central carbon metabolism pathways in the metagenomes of women with no
history of UTI versus women with active rUTI suggesting that urobiomes of healthy women are functionally
different than those with rUTI. We have assembled a multidisciplinary, collaborative team to conclusively fill
fundamental gaps in knowledge through the following specific aims: 1) Define the correlation between urinary
Lb abundance and estrogen concentration in PM women using EHT, 2) Define metabolic differences between
the urobiomes of healthy women and those with rUTI relevant to the urinary environment, and 3) Establish the
spatiotemporal dynamics of urobiome composition and function in healthy PM women and during rUTI. In
completing these aims, we will quantify excreted EHT metabolites and define their correlation with urinary Lb
abundance. We will define key, relevant metabolic differences between urobiomes and identify metabolite-taxa
associations related to rUTI. Finally, our longitudinal analysis of urinary metagenomes and metabolites in
matched patient samples will define the effect of EHT on urobiome dynamics in healthy PM women and during
rUTI. These findings will generate...

## Key facts

- **NIH application ID:** 10614131
- **Project number:** 3R01DK131267-02S1
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Nicole Janell De Nisco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $64,925
- **Award type:** 3
- **Project period:** 2021-09-30 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10614131

## Citation

> US National Institutes of Health, RePORTER application 10614131, Defining the dynamics of urobiome structure and function in postmenopausal women and its role in recurrent UTI susceptibility (3R01DK131267-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10614131. Licensed CC0.

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