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Metabolomics analysis identifies different metabotypes of asthma severity

Metabolomics analysis identifies different metabotypes of asthma severity
Metabolomics analysis identifies different metabotypes of asthma severity
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.
0903-1936
1-13
Reinke, Stacey
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Gallart-Ayala, Hector
307dceea-4127-4dff-be30-1d0b940bcffa
Gomez, Cristina
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Checa, Antonio
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Fauland, Alexander
8de02226-1a4d-45d9-b943-ab4a4fd86cc1
Naz, Shama
1c097c92-c8e5-40f9-b810-8a3dd6eeb6bd
Kamleh, Muhammed
5a41f6e0-9f7f-444a-9b78-14d64d607494
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Hinks, Timothy
c7668ed3-f706-4038-8645-ee6cc6aef29f
Wheelock, Craig
0b141710-465c-48c8-a9da-543ca3e98272
Reinke, Stacey
8ae0da28-99c5-431a-974b-b684cd3c2a3d
Gallart-Ayala, Hector
307dceea-4127-4dff-be30-1d0b940bcffa
Gomez, Cristina
3a41d9ba-46e8-4cbf-b2f4-b525a8b49095
Checa, Antonio
4e268495-7b91-4e8e-ad37-9d815401cc57
Fauland, Alexander
8de02226-1a4d-45d9-b943-ab4a4fd86cc1
Naz, Shama
1c097c92-c8e5-40f9-b810-8a3dd6eeb6bd
Kamleh, Muhammed
5a41f6e0-9f7f-444a-9b78-14d64d607494
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Hinks, Timothy
c7668ed3-f706-4038-8645-ee6cc6aef29f
Wheelock, Craig
0b141710-465c-48c8-a9da-543ca3e98272

Reinke, Stacey, Gallart-Ayala, Hector, Gomez, Cristina, Checa, Antonio, Fauland, Alexander, Naz, Shama, Kamleh, Muhammed, Djukanovic, Ratko, Hinks, Timothy and Wheelock, Craig (2017) Metabolomics analysis identifies different metabotypes of asthma severity. European Respiratory Journal, 49 (3), 1-13, [1601740]. (doi:10.1183/13993003.01740-2016).

Record type: Article

Abstract

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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Metabolomics paper Hinks KI Soton ERJ-01740-2016.pdf for eprints 16-01-2017.pdf - Version of Record
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Accepted/In Press date: 23 November 2016
e-pub ahead of print date: 29 March 2017
Published date: 2017
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 404770
URI: http://eprints.soton.ac.uk/id/eprint/404770
ISSN: 0903-1936
PURE UUID: 1cb2f709-4eb4-40a4-8f93-64f119f2f73b
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 23 Jan 2017 13:54
Last modified: 16 Mar 2024 02:36

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Contributors

Author: Stacey Reinke
Author: Hector Gallart-Ayala
Author: Cristina Gomez
Author: Antonio Checa
Author: Alexander Fauland
Author: Shama Naz
Author: Muhammed Kamleh
Author: Timothy Hinks
Author: Craig Wheelock

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