Next Article in Journal
Review on Multispectral Photoacoustic Analysis of Cancer: Thyroid and Breast
Next Article in Special Issue
NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes
Previous Article in Journal
Evaluating Cefoperazone-Induced Gut Metabolic Functional Changes in MR1-Deficient Mice
Previous Article in Special Issue
Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response
 
 
Article

Segmental Bronchial Allergen Challenge Elicits Distinct Metabolic Phenotypes in Allergic Asthma

by 1,2,†, 3,†, 1,2, 3,*,† and 4,*
1
Department of Cell and Regenerative Biology, School of Medicine and Public Health (SMPH), University of Wisconsin-Madison, Madison, WI 53705, USA
2
Human Proteomics Program, School of Medicine and Public Health (SMPH), University of Wisconsin-Madison, Madison, WI 53705, USA
3
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine and Public Health (SMPH), University of Wisconsin-Madison, Madison, WI 53705, USA
4
Institute for Clinical and Translational Research (ICTR), University of Wisconsin-Madison, Madison, WI 53705, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Brent Warren Winston, Angela Rogers, Kathleen A. Stringer and Chel Hee Lee
Metabolites 2022, 12(5), 381; https://doi.org/10.3390/metabo12050381
Received: 19 January 2022 / Revised: 30 March 2022 / Accepted: 8 April 2022 / Published: 22 April 2022
(This article belongs to the Special Issue Using Metabolomics to Subphenotype Disease and Therapeutic Response)
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. View Full-Text
Keywords: allergic asthma; saturated fatty acid synthesis; segmental bronchial antigen provocation; metabolomics; phenotype allergic asthma; saturated fatty acid synthesis; segmental bronchial antigen provocation; metabolomics; phenotype
Show Figures

Graphical abstract

MDPI and ACS Style

Zhu, Y.; Esnault, S.; Ge, Y.; Jarjour, N.N.; Brasier, A.R. Segmental Bronchial Allergen Challenge Elicits Distinct Metabolic Phenotypes in Allergic Asthma. Metabolites 2022, 12, 381. https://doi.org/10.3390/metabo12050381

AMA Style

Zhu Y, Esnault S, Ge Y, Jarjour NN, Brasier AR. Segmental Bronchial Allergen Challenge Elicits Distinct Metabolic Phenotypes in Allergic Asthma. Metabolites. 2022; 12(5):381. https://doi.org/10.3390/metabo12050381

Chicago/Turabian Style

Zhu, Yanlong, Stephane Esnault, Ying Ge, Nizar N. Jarjour, and Allan R. Brasier. 2022. "Segmental Bronchial Allergen Challenge Elicits Distinct Metabolic Phenotypes in Allergic Asthma" Metabolites 12, no. 5: 381. https://doi.org/10.3390/metabo12050381

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop