Untargeted metabolomic profiling identifies disease-specific and outcome-related signatures in chronic rhinosinusitis - 05/09/22
Abstract |
Background |
Although metabolomics provides novel insights into disease mechanisms and biomarkers, the metabolic alterations in local tissues affected by chronic rhinosinusitis (CRS) are unknown.
Objective |
This study aimed to determine the metabolomic profiles of sinonasal tissues associated with different types of CRS and their treatment outcomes.
Methods |
Untargeted metabolomic profiling was performed on sinonasal tissues obtained from patients with eosinophilic CRS with nasal polyps (CRSwNP), noneosinophilic CRSwNP or CRS without nasal polyps (CRSsNP), and controls. The messenger RNA (mRNA) levels of inflammatory cytokines in nasal tissues were detected by quantitative real-time reverse transcriptase PCR. Nasal polyp tissues were cultured ex vivo and treated with glutathione.
Results |
Distinct metabolomic profiles were observed for the CRS subtypes. Eosinophilic CRSwNP had profoundly enhanced unsaturated fatty acid oxidization, which correlated with mucosal eosinophil numbers and IL-5 mRNA levels. Noneosinophilic CRSwNP was characterized by uric acid accumulation. Increased uric acid levels were positively correlated with mucosal neutrophil numbers and IFN-γ, IL-17A, IL-1β, and IL-8 mRNA levels. Disrupted purine metabolism was specifically detected in CRSsNP. Reduced levels of amino acid metabolites were found in eosinophilic CRSwNP and CRSsNP, and were inversely associated with mucosal total inflammatory cell numbers and inflammatory cytokines. Compared to non–difficult-to-treat CRS, difficult-to-treat CRS had higher glutathione disulfide levels, which were positively correlated with IL-8 mRNA levels. Glutathione treatment reduced IL-8 mRNA expression in cultured nasal polyp tissues.
Conclusions |
Specific metabolic signatures are associated with different types of CRS, inflammatory patterns, and disease outcomes, which may provide novel insights into pathophysiologic mechanisms, subtype-specific biomarkers, and treatment targets of CRS.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Chronic rhinosinusitis, glutathione disulfide, inflammation, metabolomics, prognosis
Abbreviations used : AMP, AUC, CRS, CRSsNP, CRSwNP, Eos CRSwNP, EpOME, G-CSF, GSH, GSSG, HPODE, KEGG, mRNA, Non-Eos CRSwNP, NP, OPLS-DA, PGPC, UFA
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. |
|
| This study was supported by National Natural Science Foundation of China (NSFC) grants 82130030, 81920108011, and 81630024 (Z.L.). |
|
| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 150 - N° 3
P. 727 - septembre 2022 Retour au numéro
Article précédent
- Clinical and molecular implications of RGS2 promoter genetic variation in severe asthma
- Juan Carlos Cardet, Donghwa Kim, Eugene R. Bleecker, Thomas B. Casale, Elliot Israel, David Mauger, Deborah A. Meyers, Elizabeth Ampleford, Gregory A. Hawkins, Yaping Tu, Stephen B. Liggett, Victor E. Ortega, SARP3 investigators, Bruce Levy, Wanda Phipatanakul, Nizar Jarjour, Sally Wenzel, Mario Castro, John Fahy, Benjamin Gaston, William Teague, Serpil Erzurum, Anne-Marie Irani, Wendy Moore, Anne Fitzpatrick
- Corrigendum
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?