# Determining How a Dynamic Microbiome Contributes to Cystic Fibrosis Lung Disease

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $608,280

## Abstract

Project Summary
 Pulmonary exacerbations are a pervasive complication of chronic lung infection. These events
cause an increase in symptom severity, loss of lung function and require aggressive antibiotic
treatment. While the bacterial communities in chronically infected lungs are believed to be involved in
exacerbations, there is a poor understanding of how or why this happens. Our preliminary evidence
indicates there is a dysbiotic shift that occurs during CF pulmonary exacerbation (CFPE) to
the dominance of anaerobic bacteria. This proposal attempts to further test this hypothesis
and reveal mechanisms driving microbiome dynamics during CFPEs.
 Cystic Fibrosis (CF) is a chronic lung disease that is caused by mutations in the Cystic
Fibrosis Transmembrane Conductance Regulator gene (CFTR). These mutations cause a buildup of
mucus in the lungs due to disrupted epithelial ion transport. This abundant mucus plugs the
conducting airways, and due to the presence of bacteria, creates anaerobic environments. Although
poorly characterized as CF pathogens, anaerobic bacteria are ubiquitous in CF lungs and believed to
play a role in the disease. Our preliminary data indicates that there is a dysbiotic shift from pathogen
dominance to anaerobes during CFPE development. Antibiotic treatment kills these anaerobes
allowing the classic pathogens of CF, such as Pseudomonas aeruginosa, to again take over the lung.
We are able to reproduce these dynamics in the laboratory allowing us to directly study their cause.
This project will investigate CFPE microbial dynamics using clinical samples from patients, laboratory
experiments and mathematical modeling.
 We will collect longitudinal sputum samples from patients through exacerbation events and
analyze the microbial taxonomic composition, host response and metabolite production. In addition,
we will use a novel culture model that mimics the CF lung environment (called the WinCF model) to
test our hypothesis in vivo. WinCF can be manipulated to test the effect of chemical and biological
perturbations on the CF microbial community structure, metabolism and virulence. We will test
multiple variables on the structure and function of the CF microbial community in an attempt to
understand the drivers of dynamics observed during exacerbations. Results from these studies will be
mathematically modeled using a recently developed model of the CF microbiome growing in mucus-
plugged bronchioles. The entire project will utilize cutting edge multi-omics methods including
microbiome sequencing, metabolomics and novel bioinformatics data analysis platforms. Our
scientific rationale is that a better understanding of what causes microbial changes during CFPEs will
lead to more efficacious and targeted therapy against pathogens.

## Key facts

- **NIH application ID:** 10448246
- **Project number:** 5R01AI145925-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Robert Andrew Quinn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $608,280
- **Award type:** 5
- **Project period:** 2019-07-17 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448246

## Citation

> US National Institutes of Health, RePORTER application 10448246, Determining How a Dynamic Microbiome Contributes to Cystic Fibrosis Lung Disease (5R01AI145925-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448246. Licensed CC0.

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