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Background:  Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by different clinical features and treatment responsiveness. This study aimed to compare the serum metabolomics profiles between eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) and healthy controls (HC) and explore objective biomarkers for distinguishing eCRSwNP before surgery.   Methods:  Serum samples were collected from 33 neCRSwNP patients, 37 eCRSwNP patients, and 29 HC. Serum metabolomics profiles were investigated by ultra-high-performance liquid chromatography–mass spectrometry.   Results:  The analysis results revealed that neCRSwNP, eCRSwNP, and HC exhibited distinctive metabolite signatures. In addition, eCRSwNP could be distinguished from neCRSwNP referring to their serum metabolic profiles, and the top ten different metabolites were citrulline, choline, linoleic acid, adenosine, glycocholic acid, L-serine, triethanolamine, 4-guanidinobutyric acid, methylmalonic acid, and L-methionine, which were related to several most important pathways including arginine and proline metabolism; glycine, serine, and threonine metabolism; linoleic acid metabolism; and purine metabolism. Among these distinctive metabolites, citrulline, linoleic acid, adenosine, and 4-guanidinobutyric acid showed good predictabilities, and the serum levels of citrulline, linoleic acid, and adenosine were significantly correlated with tissue eosinophil (T-EOS) percentage and T-EOS count.   Conclusion:  eCRSwNP patients exhibited discriminative serum metabolic signatures in comparison with neCRSwNP patients and HC. These results suggested that metabolomics profiles contributed to understanding the pathophysiological mechanisms of CRSwNP and distinguishing its phenotypes

The Role of Serum Metabolomics in Distinguishing Chronic Rhinosinusitis With Nasal Polyp Phenotypes