# The Urinary Microbiota and Host Inflammation in Lower Urinary Tract Symptoms

> **NIH NIH K08** · CEDARS-SINAI MEDICAL CENTER · 2020 · $168,393

## Abstract

PROJECT SUMMARY
Storage lower urinary tract symptoms (LUTS), which include urinary urgency, frequency, nocturia, painful
urination, and bladder pressure/discomfort, refer to patient experiences when the bladder is unable hold urine
appropriately. These highly prevalent symptoms are chronic and debilitating, substantially degrading physical
activity and quality of life. Yet despite the heavy burden of storage LUTS on public health, little is understood of
the pathophysiology of these symptoms, limiting diagnosis, treatment, and prevention options.
Humans harbor diverse microbial communities that live in symbiosis with healthy hosts but are frequently altered
in disease. The role of these alterations is unclear, but mounting research suggests that microbial components
may interact with human tissue to alter organ function, tissue permeability, and even central nervous system
responsivity. We and others have used novel, state-of-the-art DNA sequencing methods to identify bacteria and
fungi residing within the urinary tract and describe global differences in urinary microbial communities in patients
with storage LUTS. We have yet to understand how these differences impact bladder pathophysiology, but our
preliminary data suggest that shifts in these microbial communities underlie or reflect storage LUTS symptoms
and correlate with increased local and systemic inflammation. We postulate that interactions of these changed
communities with the host alter local and systemic inflammation and increase immunologic activation of bladder
urothelial cells, generating inflammatory signatures characteristic of specific urinary symptoms. Based on
similarities to other inflammatory diseases, we hypothesize that this inflammation becomes pathogenic in
susceptible hosts with dysregulated microbial recognition, possibly mediated by genetic differences in host
responsiveness to microbial components. Using state-of-the-art microbial profiling techniques, we will identify
changes in urinary bacterial and fungal communities linked to storage LUTS in patients. We will also identify
disease-associated variations in inflammatory markers and urothelial activation and associate these findings with
specific microbial signatures and symptom patterns. We will perform a targeted characterization of genetic
polymorphisms associated with dysregulated inflammatory responses to microbes to explore the contribution of
host susceptibility in these conditions. Few previous studies have examined the urinary microbiota; this proposal
is the first to integrate multi-omic datasets with clinical metadata to allow the discovery of clinically useful disease
markers, microbial and inflammatory, and place them into the context of disease mechanisms and host risk
factors. This study may promote a more comprehensive understanding of storage LUTS pathogenesis,
identifying the molecular pathways that could serve as targets of new therapeutic agents. Positive results from
this study would have signif...

## Key facts

- **NIH application ID:** 10001501
- **Project number:** 5K08DK118176-02
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** A. Lenore Ackerman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,393
- **Award type:** 5
- **Project period:** 2019-09-01 → 2020-08-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001501

## Citation

> US National Institutes of Health, RePORTER application 10001501, The Urinary Microbiota and Host Inflammation in Lower Urinary Tract Symptoms (5K08DK118176-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001501. Licensed CC0.

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