Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy

Stéphanie Lejeune; Abhinav Kaushik; Ella S Parsons; Sharon Chinthrajah; Michael Snyder; Manisha Desai; Monali Manohar; Mary Prunicki; Kévin Contrepois; Philippe Gosset; Antoine Deschildre; Kari Nadeau

doi:10.1016/j.jaci.2023.09.040

Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy

J Allergy Clin Immunol. 2024 Feb;153(2):418-434. doi: 10.1016/j.jaci.2023.09.040. Epub 2023 Oct 29.

Authors

Affiliations

¹ Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; University of Lille, Pediatric Pulmonology and Allergy Department, Hôpital Jeanne de Flandre, CHU Lille, Lille, France; University of Lille, INSERM Unit 1019, CNRS UMR 9017, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France. Electronic address: stephanie.lejeune@chu-lille.fr.
² Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Mass.
³ Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.
⁴ Department of Genetics, Stanford University School of Medicine, Stanford, Calif.
⁵ Quantitative Science Unit, Department of Medicine, Stanford University School of Medicine, Stanford, Calif.
⁶ University of Lille, INSERM Unit 1019, CNRS UMR 9017, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
⁷ University of Lille, Pediatric Pulmonology and Allergy Department, Hôpital Jeanne de Flandre, CHU Lille, Lille, France; University of Lille, INSERM Unit 1019, CNRS UMR 9017, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
⁸ Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Mass.

PMID: 38344970
DOI: 10.1016/j.jaci.2023.09.040

Abstract

Background: Asthma and other atopic disorders can present with varying clinical phenotypes marked by differential metabolomic manifestations and enriched biological pathways.

Objective: We sought to identify these unique metabolomic profiles in atopy and asthma.

Methods: We analyzed baseline nonfasted plasma samples from a large multisite pediatric population of 470 children aged <13 years from 3 different sites in the United States and France. Atopy positivity (At⁺) was defined as skin prick test result of ≥3 mm and/or specific IgE ≥ 0.35 IU/mL and/or total IgE ≥ 173 IU/mL. Asthma positivity (As⁺) was based on physician diagnosis. The cohort was divided into 4 groups of varying combinations of asthma and atopy, and 6 pairwise analyses were conducted to best assess the differential metabolomic profiles between groups.

Results: Two hundred ten children were classified as At^-As^-, 42 as At⁺As^-, 74 as At^-As⁺, and 144 as At⁺As⁺. Untargeted global metabolomic profiles were generated through ultra-high-performance liquid chromatography-tandem mass spectroscopy. We applied 2 independent machine learning classifiers and short-listed 362 metabolites as discriminant features. Our analysis showed the most diverse metabolomic profile in the At⁺As⁺/At^-As^- comparison, followed by the At^-As⁺/At^-As^- comparison, indicating that asthma is the most discriminant condition associated with metabolomic changes. At⁺As⁺ metabolomic profiles were characterized by higher levels of bile acids, sphingolipids, and phospholipids, and lower levels of polyamine, tryptophan, and gamma-glutamyl amino acids.

Conclusion: The At⁺As⁺ phenotype displays a distinct metabolomic profile suggesting underlying mechanisms such as modulation of host-pathogen and gut microbiota interactions, epigenetic changes in T-cell differentiation, and lower antioxidant properties of the airway epithelium.

Keywords: Asthma; atopy; bile acids; children; gamma-glutamyl amino acids; metabolomics; phospholipids; polyamine; sphingolipids; tryptophan.

MeSH terms

Asthma* / epidemiology
Child
Humans
Hypersensitivity, Immediate*
Immunoglobulin E
Metabolome
Metabolomics / methods

Substances

Immunoglobulin E