# Dysbiosis of the Sinus Microbiota in Chronic Rhinosinusitis

> **NIH NIH K08** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $158,814

## Abstract

PROJECT SUMMARY:
Chronic rhinosinusitis (CRS) is a chronic airway disease defined as persistent inflammation and infection of the
nasal and sinus mucosa. Mounting evidence suggests that a microbial imbalance (dysbiosis) is associated with
disease pathogenesis, yet the complex interaction between the sinus microbiota and host environment (including
dysfunctional mucociliary clearance (MCC)) is poorly understood. Additionally, it is unclear how the local milieu
created through ineffective mucus transport supports and sustains bacterial growth in vivo. The fundamental
hypothesis of this proposal is that CRS develops through a defined series of dependent events: 1) impaired
mucus clearance, 2) generation of dysbiosis (predominantly anaerobic bacterial growth), 3) mucin degradation
to carbon-source nutrients, and 4) proliferation of sinus pathogens. The following specific aims are proposed to
test this hypothesis:
(1) Evaluate the contribution of mucin-fermenting anaerobes to recalcitrant CRS progression. Our
 specific hypothesis is that abundance of carbon-source nutrients (generated from abundant
mucinfermenting anaerobes) in CRS patients with Pseudomonas correlates to markers of CRS severity.
(2) Determine the impact of the carbon-source nutrient (acetate) on the development of Pseudomonas
 sinusitis. Our specific hypothesis is that rabbits inoculated with wild type P. aeruginosa will demonstrate the
most severe sinusitis when acetate is available.
(3) Assess whether the transfer of healthy mucus with baseline mucin metabolites and commensal
 microbiota can reverse disease progression. Our specific hypothesis is that transfer of mucus
containing baseline SCFAs and healthy microbiota will restore sinus health and reverse rabbit sinusitis
disease progression.
Overall, we anticipate that this proposal will yield critical understanding of CRS pathogenesis and establish new
and important knowledge regarding anaerobic bacteria in disease progression. We believe the innovative rabbit
model of CRS created by our laboratory is ideally suited for the proposed pre-clinical studies and will unlock the
pathogenic mechanism leading to chronic inflammation and infection in CRS. Organisms typically defined as
commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens
otherwise unable to obtain a carbon source for growth in the sinus. Targeting mucin-fermenting anaerobes and
their metabolites is a novel therapeutic strategy for the treatment of CRS. Restoring the microbial community in
diseased sinuses by mucus transfer represents a highly valued, inexpensive and safe therapy for CRS. Such a
therapy could reduce antibiotic prescriptions and combat the rising incidence of antibiotic resistance.

## Key facts

- **NIH application ID:** 10165486
- **Project number:** 5K08AI146220-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Do-Yeon Cho
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $158,814
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165486

## Citation

> US National Institutes of Health, RePORTER application 10165486, Dysbiosis of the Sinus Microbiota in Chronic Rhinosinusitis (5K08AI146220-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10165486. Licensed CC0.

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