Metabolomics analysis identifies different metabotypes of asthma severity
AuthorReinke, SN; Gallart-Ayala, H; Gomez, C; Checa, A; Fauland, A; Naz, S; Kamleh, MA; Djukanovic, R; Hinks, TSC; Wheelock, CE
Source TitleEuropean Respiratory Journal
PublisherEUROPEAN RESPIRATORY SOC JOURNALS LTD
University of Melbourne Author/sHINKS, TIMOTHY
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsReinke, S. N., Gallart-Ayala, H., Gomez, C., Checa, A., Fauland, A., Naz, S., Kamleh, M. A., Djukanovic, R., Hinks, T. S. C. & Wheelock, C. E. (2017). Metabolomics analysis identifies different metabotypes of asthma severity. EUROPEAN RESPIRATORY JOURNAL, 49 (3), https://doi.org/10.1183/13993003.01740-2016.
Access StatusOpen Access
In this study, we sought to determine whether asthma has a metabolic profile and whether this profile is related to disease severity.We characterised the serum from 22 healthy individuals and 54 asthmatics (12 mild, 20 moderate, 22 severe) using liquid chromatography-high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted mass spectrometry assays of eicosanoids, sphingolipids and free fatty acids.We conclusively identified 66 metabolites; 15 were significantly altered with asthma (p≤0.05). Levels of dehydroepiandrosterone sulfate, cortisone, cortisol, prolylhydroxyproline, pipecolate and N-palmitoyltaurine correlated significantly (p<0.05) with inhaled corticosteroid dose, and were further shifted in individuals treated with oral corticosteroids. Oleoylethanolamide increased with asthma severity independently of steroid treatment (p<0.001). Multivariate analysis revealed two patterns: 1) a mean difference between controls and patients with mild asthma (p=0.025), and 2) a mean difference between patients with severe asthma and all other groups (p=1.7×10-4). Metabolic shifts in mild asthma, relative to controls, were associated with exogenous metabolites (e.g. dietary lipids), while those in moderate and severe asthma (e.g. oleoylethanolamide, sphingosine-1-phosphate, N-palmitoyltaurine) were postulated to be involved in activating the transient receptor potential vanilloid type 1 (TRPV1) receptor, driving TRPV1-dependent pathogenesis in asthma.Our findings suggest that asthma is characterised by a modest systemic metabolic shift in a disease severity-dependent manner, and that steroid treatment significantly affects metabolism.
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