Title :

Segmental Bronchial Allergen Challenge Elicits Distinct Metabolic Phenotypes in Allergic Asthma

Author(s) :

Zhu, Yanlong [Auteur]
University of Wisconsin School of Medicine and Public Health
Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Ge, Ying [Auteur]
University of Wisconsin-Madison
University of Wisconsin School of Medicine and Public Health
Jarjour, Nizar N [Auteur]
University of Wisconsin School of Medicine and Public Health
Brasier, Allan R [Auteur]

Journal title :

Metabolites

Abbreviated title :

Metabolites

Volume number :

12

Publisher :

MDPI

Publication date :

2022-04-22

Article status :

Publié

ISSN :

2218-1989

English keyword(s) :

allergic asthma
metabolomics
phenotype
saturated fatty acid synthesis
segmental bronchial antigen provocation

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Asthma is a complex syndrome associated with episodic decompensations provoked by aeroallergen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately ...
Show more >Asthma is a complex syndrome associated with episodic decompensations provoked by aeroallergen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bronchoalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial allergen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by pathway analysis and correlation with airway inflammation. SBP-Ag induced statistically significant changes in 549 features that mapped to 72 uniquely identified metabolites. From these features, two distinct inducible metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that informed the presence of asthma-relevant pathways, including unsaturated fatty acid production/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen challenge induces distinct metabolic responses in humans, providing insight into pathogenic and protective endotypes in allergic asthma.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-18T11:46:56Z
2024-05-23T09:46:16Z