Metabolomics Reveals Altered Metabolic Pathways in Experimental Asthma

Abstract

Metabolomics refers to the comprehensive analysis of metabolites in biological systems, and has been employed to study patients with asthma based on their urinary metabolite profile. We hypothesize that airway allergic asthma would affect metabolism in the lungs, and could be detected in bronchoalveolar lavage (BAL) fluid (BALF) using a combined liquid chromatography- and gas chromatography-mass spectrometry (MS) platform. The objective of this study was to investigate changes of lung metabolism in allergic asthma by metabolomic analysis of BALF. BALB/c mice were sensitized and challenged with ovalbumin to develop experimental asthma. Dexamethasone was administered to study the effects of corticosteroids on lung metabolism. Metabolites in BALF were measured using liquid chromatography-MS and gas chromatography-MS, and multivariate statistical analysis was performed by orthogonal projections to latent structures discriminant analysis. Metabolomic analysis of BALF from ovalbumin-challenged mice revealed novel changes in metabolic pathways in the lungs as compared with control animals. These metabolite changes suggest alterations of energy metabolism in asthmatic lungs, with increases of lactate, malate, and creatinine and reductions in carbohydrates, such as mannose, galactose, and arabinose. Lipid and sterol metabolism were affected with significant decreases in phosphatidylcholines, diglycerides, triglycerides, cholesterol, cortol, and cholic acid. Dexamethasone treatment effectively reversed many key metabolite changes, but was ineffective in repressing lactate, malate, and creatinine, and induced additional metabolite changes. Metabolomic analysis of BALF offers a promising approach to investigating allergic asthma. Our overall findings revealed considerable pathway changes in lung metabolism in asthmatic lungs, including energy, amino acids, and lipid metabolism.