# The Microbiota of the Pediatric CF Airway: What role does it play?

> **NIH NIH R01** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $363,830

## Abstract

Project Summary/Abstract
Progressive, obstructive lung disease remains the biggest cause of morbidity and early mortality in cystic
fibrosis (CF). Early detection and treatment of pulmonary decline is key to optimal long-term outcome;
however, physiologic measures of lung function and radiologic outcomes fail to capture the inflammation and
infection that begin in infancy, which are often asymptomatic. Mucus stasis and impaired bacterial killing
provide the optimal environment for chronic bacterial infection in the CF airway. Culture-independent
approaches using next-generation sequencing techniques have revealed a more complex, polymicrobial
community in the CF airway than previously identified using traditional culture. Interestingly, a large number of
these communities are anaerobes, known to inhabit the oral cavity and thought to be non-pathogenic.
Recently, anaerobes in CF sputum were found to generate a nutritional environment through fermentative
metabolism and mucin degradation that facilitates the growth and persistence of bacterial pathogens like
Pseudomonas aeruginosa, a known contributor to lung function decline in CF. Surprisingly, Dr. Laguna has
found that anaerobes are already present in higher relative abundance compared to traditional CF pathogens
in the lower airways of infants with CF; however, we do not yet understand their contribution in the
development of early lung disease. The key question remains whether the early presence of anaerobic
bacteria in the lower airways of CF infants predisposes them to a more rapid decline in lung function, more
frequent pulmonary exacerbations or structural lung damage. Therefore, the central hypothesis of this
proposal is that anaerobic bacteria in the lower airways of infants and children with CF is associated
with fermentative metabolism and will have a unique metabolic and metaproteomic biosignature that
incites inflammation and contributes to the development of early CF lung disease. This research takes
advantage of the team's expertise and established collaborations with experts in the field as well as a unique
and valuable resource: a collection of bronchoalveolar lavage fluid (BALF) samples from children with/without
CF available for immediate analysis. The aims of this project are three-fold: First, through the measurement of
fermentation and mucin products, to determine if anaerobic communities in BALF associate with a fermentative
environment in the CF airway. Second, to determine if the lower airway microbiota is associated with the
metabolomic profile measured in BALF from young children with/without CF. Third, through innovative
metaproteomics technology, to characterize the metaproteome to determine the metabolic activity of the
microbial communities in the CF airway. The knowledge gained upon completion of this project would allow
healthcare providers to consider anaerobic specific antibiotics or encourage the development of new
antimicrobials targeting bacterial fermentativ...

## Key facts

- **NIH application ID:** 9927663
- **Project number:** 5R01HL136499-03
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Theresa A Laguna
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,830
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927663

## Citation

> US National Institutes of Health, RePORTER application 9927663, The Microbiota of the Pediatric CF Airway: What role does it play? (5R01HL136499-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927663. Licensed CC0.

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