Inflammation in children with cystic fibrosis: contribution of bacterial production of long-chain fatty acids

Erin Felton,Keith A Crandall,Iman Sami,Robert J Freishtat,Andrea Hahn,Aszia Burrell,Hollis Chaney,Anastassios C Koumbourlis

doi:10.1038/s41390-021-01419-4

Abstract

BackgroundCystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status.MethodsRespiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status.ResultsThe mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001).ConclusionsLCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF.ImpactIncreased levels of LCFAs are found after IV antibiotic treatment in persons with CF.LCFAs have previously been associated with increased lung inflammation in asthma.This is the first report of LCFAs in the airway of persons with CF.This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF.Future studies should evaluate LCFAs as predictors of future PExs.

Highlights

Cystic fibrosis (CF) is an autosomal recessive disease affecting >30,000 people in the United States and 70,000 people worldwide.[1,2] Lung disease in CF patients is characterized by chronic and intermittent acute lung infections
Pulmonary function was improved at the end of antibiotic treatment and follow-up compared to pulmonary exacerbations (PExs), not significantly (FEV1 p = 0.303, forced vital capacity (FVC) p = 0.099, and FEF25–75 p = 0.267)
Bacterial metabolic pathways across changes in clinical status Generally, we found that pathways related to bacterial metabolic pathways of biosynthesis, degradation/utilization, and fermentation were differentially present based on clinical status (Fig. 4)

Summary

Introduction

Cystic fibrosis (CF) is an autosomal recessive disease affecting >30,000 people in the United States and 70,000 people worldwide.[1,2] Lung disease in CF patients is characterized by chronic and intermittent acute lung infections Sequela of these infections leads to an increase in respiratory symptoms accompanied by an acute decrease in lung function known as pulmonary exacerbations (PExs).[3] Staphylococcus aureus and Pseudomonas aeruginosa remain the most common bacterial pathogens identified in routine culture and are thought to contribute to both lung inflammation and PEx.[2,4] PEx occurs in patients with CF at all ages, and while advances in pulmonary and antibiotic therapy continue to extend the life of CF patients, PExs are still the main cause of morbidity, mortality, and decreased quality of life.[1,5].

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