title: Metabolomics Reveals Inflammatory-Linked Pulmonary Metabolic Alterations in a Murine Model of House Dust Mite-Induced Allergic Asthma.
abstract: 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.
authors: Singapore-MIT Alliance for Research and Technology (SMART), Singapore 138602.
authors: Wanxing Eugene
authors: WE
authors: Ho
authors: Key Laboratory of Insect Development and Evolutionary Biology, Chinese Academy of Sciences , Shanghai 200032, China.
authors: Yong-Jiang
authors: YJ
authors: Xu
authors: Department of Gastroenterology & Hepatology, Singapore General Hospital , Singapore 169608.
authors: Chang
authors: C
authors: Cheng
authors: Hong Yong
authors: HY
authors: Peh
authors: Singapore-MIT Alliance for Research and Technology (SMART), Singapore 138602.|Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors: Steven R
authors: SR
authors: Tannenbaum
authors: W S Fred
authors: WSF
authors: Wong
authors: Choon Nam
authors: CN
authors: Ong
keywords: allergy; corticosteroids; gas chromatography; inflammation; liquid chromatography; mass spectrometry; metabolome