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. 2025 Oct 25;21(6):153.
doi: 10.1007/s11306-025-02355-8.

Metabolomic profiling reveals distinct lipid signatures in progressive versus stable fibrotic lung disease

Faizan Faizee  1   2 , Zachary Smith  3   4 , Olga Gomez  5   6 , Zaid Alnabulsi  5   6 , Glenn Pottmeyer  5   6 , Nadia Ashrafi  6   7 , Romana Ashrafi Mimi  6   7 , Vilija Lomeikaite  8 , Miglė Gabrielaitė  8 , Karolis Krinickis  8 , Juozas Gordevičius  8 , Ali Yilmaz  6   7   9 , Edward Castillo  10 , Stewart F Graham  6   7   9 , Girish B Nair  11
Affiliations

Metabolomic profiling reveals distinct lipid signatures in progressive versus stable fibrotic lung disease

Faizan Faizee et al. Metabolomics. .

Abstract

Objective: To compare the metabolomic profile differences between ILD (interstitial lung disease) and chronic obstructive pulmonary disease (COPD) controls, and to distinguish profiles between progressive and stable idiopathic pulmonary fibrosis (IPF)/ILD subjects.

Methods: This single-center prospective study enrolled n = 71 (progressive IPF/ILD: n = 33, stable IPF/ILD: n = 27, COPD: n = 11) participants between December 2021 and October 2022. Metabolite quantification was performed using the liquid chromatography-mass spectrometry (LC-MS platform), and nuclear magnetic resonance spectroscopy (1H NMR). Further, pathway enrichment analysis was performed to identify biochemical pathways associated with the disease.

Results: 715 metabolites were accurately quantified to investigate (a) differences between the combined groups of stable and progressive idiopathic pulmonary fibrosis IPF/ILD and COPD controls, and (b) differences between progressive IPF/ILD and stable IPF/ILD controls. The most notable metabolites distinguishing fibrotic lung disease (both stable and progressive IPF/ILD) from COPD were glycerolipids (GL). Enrichment analysis of IPF/ILD versus COPD revealed significant disruptions in lipid metabolic pathways, particularly glycerophospholipids, and sphingolipids (false discovery rate FDR q-value < 0.05). In addition, significant disruptions in TG species were found in progressive IPF/ILD with enrichment analysis revealing dysregulation of metabolic pathways associated with glycerophospholipids (FDR q-value < 0.05).

Conclusion: These findings emphasize the dysregulation of lipid metabolism in fibrotic lung diseases, involving glycerolipids, glycerophospholipids, and sphingolipids. The distinct lipid alterations identified through metabolomic profiling provide valuable insight into lipid metabolism in IPF/ILD, warranting further research to explore their potential as biomarkers.

Keywords: 1H NMR; Biocrates Quant 500 XL; Idiopathic pulmonary fibrosis; Interstitial lung disease; Lung fibrosis; Mass spectrometry; Metabolomics; Progressive pulmonary fibrosis.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: This study was conducted in full compliance with ethical standards and was approved by the Institutional Review Board (IRB) of Corewell Health East William Beaumont University Hospital (IRB 2021-327).

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