Distinctive metabolic profiles between Cystic Fibrosis mutational subclasses and lung function

Metabolomics. 2021 Jan 4;17(1):4. doi: 10.1007/s11306-020-01760-5.


Introduction: Cystic fibrosis (CF) is a lethal multisystemic disease of a monogenic origin with numerous mutations. Functional defects in the cystic fibrosis transmembrane conductance receptor (CFTR) protein based on these mutations are categorised into distinct classes having different clinical presentations and disease severity.

Objectives: The present study aimed to create a comprehensive metabolomic profile of altered metabolites in patients with CF, among different classes and in relation to lung function.

Methods: A chemical isotope labeling liquid chromatography-mass spectrometry metabolomics was used to study the serum metabolic profiles of young and adult CF (n = 39) patients and healthy controls (n = 30). Comparisons were made at three levels, CF vs. controls, among mutational classes of CF, between CF class III and IV, and correlated the lung function findings.

Results: A distinctive metabolic profile was observed in the three analyses. 78, 20, and 13 significantly differentially dysregulated metabolites were identified in the patients with CF, among the different classes and between class III and IV, respectively. The significantly identified metabolites included amino acids, di-, and tri-peptides, glutathione, glutamine, glutamate, and arginine metabolism. The top significant metabolites include 1-Aminopropan-2-ol, ophthalmate, serotonin, cystathionine, and gamma-glutamylglutamic acid. Lung function represented by an above-average FEV1% level was associated with decreased glutamic acid and increased guanosine levels.

Conclusion: Metabolomic profiling identified alterations in different amino acids and dipeptides, involved in regulating glutathione metabolism. Two metabolites, 3,4-dihydroxymandelate-3-O-sulfate and 5-Aminopentanoic acid, were identified in common between the three anlayses and may represent as highly sensitive biomarkers for CF.

Keywords: Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; FEV1%; Liquid chromatography-mass spectrometry; Metabolomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers*
  • Case-Control Studies
  • Chromatography, Liquid
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / metabolism*
  • Humans
  • Mass Spectrometry
  • Metabolome*
  • Metabolomics* / methods
  • Mutation*
  • Respiratory Function Tests
  • Severity of Illness Index


  • Biomarkers