Abstract: Equine asthma is a chronic, non-infectious inflammatory disease of the lower airways in horses, classified as mild to moderate (MEA) or severe (SEA). Its pathogenesis is not fully understood and is influenced by environmental and seasonal factors. In this cross-sectional study, seasonal effects on the bronchoalveolar lavage fluid (BALF) metabolome were investigated in asthmatic and non-asthmatic horses. The metabolome of 230 BALF samples from horses across different seasons, classified as cytologically unremarkable (CUA), MEA, or SEA, was analyzed using proton nuclear magnetic resonance spectroscopy (1H-NMR). Principal component analysis was performed for each season, and metabolite profiles were statistically compared between seasons within each group. Altered metabolites were subjected to pathway enrichment analysis using the FELLA R package. Asthmatic horses showed significant seasonal changes in metabolite concentrations between warm and cold seasons, whereas only trends were observed in CUA horses. Pathway analysis indicated enrichment of cholesterol metabolism across all groups. The mTOR signaling pathway was only enriched in SEA horses. Several metabolites-including valine, taurine and carnitine -were altered during the transition from winter to spring in asthmatic horses. These findings indicate that the winter to spring transition significantly modulates the airway metabolome in asthmatic horses, particularly in SEA-affected animals.
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Overview
This study investigates how seasonal changes, specifically the transition from winter to spring, affect the airway metabolome of horses with asthma.
It compares metabolite profiles in the bronchoalveolar lavage fluid (BALF) of asthmatic and non-asthmatic horses, revealing significant metabolic shifts in asthmatic horses linked to disease severity and pathways such as cholesterol metabolism and mTOR signaling.
Background and Objectives
Equine asthma is a chronic inflammatory disease affecting the lower airways of horses and is classified into mild to moderate asthma (MEA) and severe asthma (SEA).
The exact causes and mechanisms (pathogenesis) of equine asthma remain unclear but are known to be impacted by environmental and seasonal factors.
The objective of this study was to analyze the effect of seasonal changes on the airway metabolome—the collection of small molecules and metabolites—in horses with and without asthma.
Specifically, they examined differences between the warm and cold seasons to understand how seasonal transition affects the biochemical environment in the airways.
Methods
Samples: Bronchoalveolar lavage fluid (BALF) samples were collected from 230 horses representing different asthma classifications: cytologically unremarkable (CUA, non-asthmatic), mild to moderate equine asthma (MEA), and severe equine asthma (SEA).
Analytical Technique: The metabolome of BALF samples was analyzed using proton nuclear magnetic resonance spectroscopy (1H-NMR), a technique that detects and quantifies metabolites based on their magnetic properties.
Data Analysis: Principal component analysis (PCA) was conducted separately for each season to identify patterns in metabolite profiles.
Comparisons: Metabolite concentrations between seasons (e.g., winter vs. spring) were statistically compared within each horse group (CUA, MEA, SEA).
Pathway Analysis: Metabolites showing significant changes were analyzed using the FELLA R package, which maps metabolites to relevant biochemical pathways to interpret their biological significance.
Key Findings
Seasonal Impact:
Asthmatic horses (MEA and SEA) exhibited significant changes in concentrations of airway metabolites when transitioning from cold seasons (e.g., winter) to warm seasons (e.g., spring).
Non-asthmatic horses (CUA) showed only minor trends without significant metabolomic changes.
Metabolic Pathways:
Cholesterol metabolism was enriched in all groups, indicating its importance in airway biochemistry regardless of asthma status or season.
The mTOR signaling pathway, which is involved in cell growth and inflammation, was specifically enriched only in horses with severe equine asthma (SEA).
Specific Metabolites:
Valine, an essential amino acid involved in protein synthesis and energy metabolism, was altered during the seasonal transition in asthmatic horses.
Taurine, an amino sulfonic acid that plays roles in antioxidant defense and osmoregulation, showed changes indicating potential involvement in airway response to seasonal triggers.
Carnitine, critical in fatty acid metabolism and energy production, also demonstrated altered levels, suggesting shifts in metabolic demands or inflammation.
Interpretation and Implications
The clear metabolic changes in asthmatic horses during winter to spring transition reflect underlying biological adaptations or exacerbations linked to environmental factors such as allergens, temperature, and humidity changes.
Enrichment of cholesterol metabolism across all groups highlights a fundamental role of lipid metabolism in airway health and disease.
The activation of mTOR signaling specifically in severe asthma cases suggests that more profound inflammatory or cellular remodeling processes are occurring, which might be targets for therapeutic interventions.
Changes in valine, taurine, and carnitine indicate shifts in protein synthesis, antioxidant defense, and energy metabolism, which could provide insights into managing or monitoring equine asthma seasonally.
Overall, these findings emphasize the importance of considering seasonal variation when evaluating and treating equine asthma and suggest metabolomics as a useful tool for understanding disease dynamics.
Cite This Article
APA
Drespling J, Heelemann S, Strathmeyer S, Kühn H, Schwarz B, Mundhenk L.
(2026).
The transition from winter to spring has an impact on the airway metabolome profile of asthmatic horses.
PLoS One, 21(4), e0346250.
https://doi.org/10.1371/journal.pone.0346250
Liu Y, Zhang X, Zhang L, Oliver BG, Wang HG, Liu ZP. Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma.. Allergy Asthma Immunol Res 2022;14(4):393–411.
Santos A, Pité H, Chaves-Loureiro C, Rocha SM, Taborda-Barata L. Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications.. Metabolites 2021;11(8):534.
Maniscalco M, Paris D, Melck DJ, D’Amato M, Zedda A, Sofia M. Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype.. J Allergy Clin Immunol 2017;139(5):1536-1547.e5.
Liu Y, Zheng J, Zhang HP, Zhang X, Wang L, Wood L. Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study.. Allergy Asthma Immunol Res 2018;10(6):628–47.
Bar N, Korem T, Weissbrod O, Zeevi D, Rothschild D, Leviatan S. A reference map of potential determinants for the human serum metabolome.. Nature 2020;588(7836):135–40.
Yurekten O, Payne T, Tejera N, Amaladoss FX, Martin C, Williams M. MetaboLights: open data repository for metabolomics.. Nucleic Acids Res 2024;52(D1):D640–6.
Dona AC, Kyriakides M, Scott F, Shephard EA, Varshavi D, Veselkov K. A guide to the identification of metabolites in NMR-based metabonomics/metabolomics experiments.. Comput Struct Biotechnol J 2016;14:135–53.
Dieterle F, Ross A, Schlotterbeck G, Senn H. Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics.. Anal Chem 2006;78(13):4281–90.
Walker HK, Ottka C, Lohi H, Handel I, Clements DN, Gow AG. Seasonal variation in serum metabolites of northern European dogs. J Vet Intern Med 2022;36(1):190–5.
Schramm PJ, Brown CL, Saha S, Conlon KC, Manangan AP, Bell JE. A systematic review of the effects of temperature and precipitation on pollen concentrations and season timing, and implications for human health. Int J Biometeorol 2021;65(10):1615–28.
Kudrna KM, Vilches LF, Eilers EM, Maurya SK, Brody SL, Horani A. MTOR signaling regulates the development of airway mucous cell metaplasia associated with severe asthma. JCI Insight 2025;10(13):e187904.
Chang C, Guo Z, He B, Yao W. Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis. Acta Pharmacol Sin 2015;36(11):1356–66.
Barschak AG, Sitta A, Deon M, de Oliveira MH, Haeser A, Dutra-Filho CS. Evidence that oxidative stress is increased in plasma from patients with maple syrup urine disease. Metab Brain Dis 2006;21(4):279–86.
Cortijo J, Blesa S, Martinez-Losa M, Mata M, Seda E, Santangelo F. Effects of taurine on pulmonary responses to antigen in sensitized Brown-Norway rats. Eur J Pharmacol 2001;431(1):111–7.
Xiang F, Zhang Z, Xie J, Xiong S, Yang C, Liao D. Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: beyond fatty acid oxidation.. J Transl Med 2025;23(1):324.
Selo MA, Sake JA, Ehrhardt C, Salomon JJ. Organic Cation Transporters in the Lung-Current and Emerging (Patho)Physiological and Pharmacological Concepts.. Int J Mol Sci 2020;21(23):9168.
Mirji G, Worth A, Bhat SA, El Sayed M, Kannan T, Goldman AR. The microbiome-derived metabolite TMAO drives immune activation and boosts responses to immune checkpoint blockade in pancreatic cancer.. Sci Immunol 2022;7(75):eabn0704.
Cabrera D, Fraser K, Roy NC. A metabolomics analysis of interspecies and seasonal trends in ruminant milk: The molecular difference between bovine, caprine, and ovine milk.. J Dairy Sci 2024;107(9):6511–27.
Kelly RS, Dahlin A, McGeachie MJ, Qiu W, Sordillo J, Wan ES. Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic.. Chest 2017;151(2):262–77.