Metabolomics Reveals Inflammatory-Linked Pulmonary Metabolic Alterations in a Murine Model of House Dust Mite-Induced Allergic Asthma.

Although the house dust mite (HDM) is a major environmental aeroallergen that promotes the pathogenesis and severity of allergic asthma, it remains elusive if HDM exposures can induce global metabolism aberrations during allergic airway inflammation. Using an integrated gas and liquid chromatography mass spectrometry-based metabolomics and multiplex cytokine profile analysis, metabolic alterations and cytokine changes were investigated in the bronchoalveolar lavage fluid (BALF), serum, and lung tissues in experimental HDM-induced allergic asthma. Allergic pulmonary HDM exposures lead to pronounced eosinophilia, neutrophilia, and increases in inflammatory cytokines. Metabolomics analysis of the BALF, serum, and lung tissues revealed distinctive compartmental metabolic signatures, which included depleted carbohydrates, increased energy metabolites, and consistent losses of sterols and phosphatidylcholines. Pearson correlation analysis uncovered strong associations between specific metabolic alterations and inflammatory cells and cytokines, linking altered pulmonary metabolism to allergic airway inflammation. The clinically prescribed glucocorticoid prednisolone could modulate airway inflammation but was ineffective against the reversal of many HDM-induced metabolic alterations. Collectively, metabolomics reveal comprehensive pulmonary metabolic signatures in HDM-induced allergic asthma, with specific alterations in carbohydrates, lipids, sterols, and energy metabolic pathways. Altered pulmonary metabolism may be a major underlying molecular feature involved during HDM-induced allergic airway inflammation, linked to inflammatory cells and cytokines changes.