A pilot metabolomics study across the continuum of interstitial lung disease fibrosis severity.

Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE

Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-

Metabolomics*/methods ; Lung Diseases, Interstitial*/metabolism ; Lung Diseases, Interstitial*/blood ; Idiopathic Pulmonary Fibrosis*/metabolism ; Idiopathic Pulmonary Fibrosis*/pathology ; Idiopathic Pulmonary Fibrosis*/blood; Humans ; Male ; Female ; Middle Aged ; Pilot Projects ; Aged ; Biomarkers/blood

Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high-resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non-fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non-IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group-wise analyses of metabolites altered in ILD phenotypes. We utilized limma one-way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p-values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl-hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non-ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis.
(© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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R01 ES031980 United States ES NIEHS NIH HHS; P30 ES019776 United States ES NIEHS NIH HHS; DK125246 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Keywords: lung disease; metabolic disruption; pathway enrichment analysis; pulmonary fibrosis

0 (Biomarkers)

Date Created: 20241018 Date Completed: 20241018 Latest Revision: 20241021

20241021

PMC11489002

10.14814/phy2.70093

39424430