# Mechanistic basis of urinary Lactobacillus enrichment by estrogen hormone therapy

> **NIH NIH F32** · UNIVERSITY OF TEXAS DALLAS · 2022 · $67,582

## Abstract

Proposal Summary/Abstract
 The medical burden of urinary tract infection (UTI) is significant as they directly contribute to 1% of all clinical
visits in the United States. Annual medical expenses attributed to UTI currently exceed $3.5 billion. As a global
health concern, UTIs mainly affect women and commonly progress into recurrent UTI (rUTI) when a patient
experiences 3 or more UTIs in a 12 month period. The risk of rUTI increases with age, leading to
disproportionately high incidence rates in postmenopausal (PM) women. Effective therapies for rUTI are severely
limited as most treatment strategies rely on long-term antibiotic therapy with the goal of achieving sterility within
the urinary tract. However, even healthy urine is not sterile, and it has been confirmed that a microbial community
resides in the healthy urinary tract of PM women, termed here the urobiome. To date, most therapeutic strategies
for rUTI do not consider the preservation or restoration of the resident microbiota of the urinary or urogenital
tract. Interestingly, the urobiome has been shown to be interconnected with the vaginal microbiome and vaginal
D(-)Lactate-producing lactobacilli, such as Lactobacillus crispatus, have been shown to protect against bacterial
vaginosis. Vaginal lactobacilli have been associated with circulating estrogen levels and early clinical studies
found that estrogen hormone therapy (EHT) is strongly associated with vaginal lactobacilli enrichment in PM
women. Interestingly, EHT is now widely becoming recognized as an effective treatment option for rUTI in PM
women, but the mechanism behind this observation is unknown. We have observed a strong association
between EHT use and urinary L. crispatus enrichment in our metagenomic analysis of the urobiome of a
controlled cross-sectional cohort of PM women (n=75). These observations have led me to ask a fundamental
question: How does estrogen enrich for Lactobacillus communities in the urobiome? This proposal centers
around the following hypothesis: EHT, as a treatment for rUTI, enhances Lactobacillus colonization of the
urinary tract by stimulating host production of nutrient sources and scaffolding attachment sites needed
for colonization. To test these hypotheses, I will characterize the effect of EHT treatment on the metabolism of
cultured primary urothelial cells and use a curated biobank of bacterial isolates from our de-identified human
cohorts to study colonization of co-cultures of urothelial cells and L. crispatus in the presence and absence of
estrogen. The long-term goal of this proposal is to leverage the insight gained from testing these hypotheses to
identify alternate therapeutic targets for effective and safe adjunct therapies for rUTI. A central theme of this
proposal is to use the scientific goals as a vehicle to achieve critical training goals I and my sponsors believe will
greatly help in my future independent research career.

## Key facts

- **NIH application ID:** 10537389
- **Project number:** 1F32DK128975-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Michael Lee Neugent
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537389

## Citation

> US National Institutes of Health, RePORTER application 10537389, Mechanistic basis of urinary Lactobacillus enrichment by estrogen hormone therapy (1F32DK128975-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10537389. Licensed CC0.

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