{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:27:11Z","timestamp":1784838431879,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sudden sensorineural hearing loss (SSNHL) is a common otological disorder with complex etiologies and unclear pathophysiology. This study aimed to detect and analyze plasma metabolites in SSNHL, identify potential biomarkers, and uncover underlying metabolic mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cohort of 64 SSNHL, classified into four subtypes (low-frequency, high-frequency, flat and total deafness type), and 53 normal controls (NC) were recruited. Plasma samples were collected and analyzed by high-performance liquid chromatography-mass spectrometry (LC-MS). Metabolite profiling was performed, followed by multivariate statistical analyses, including orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and partial least-squares discriminant analysis (PLS-DA) to find differentially expressed metabolites between the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed significant differences in the plasma metabolome when comparing each of the four SSNHL types with NC. A total of 130 differentially expressed metabolites were identified, with sphingosine, anthranilic acid, and 6-hydroxyflavanone (6-HF) being prominent examples. Were prominent. Pathway enrichment analysis indicated that these metabolites were mainly involved in central carbon metabolism, protein digestion and absorption, aminoacyl-tRNA biosynthesis, mineral absorption, etc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings imply that plasma metabolite profiling holds promise as a non-invasive approach for screening biomarkers in SSNHL. The identified differential metabolites and associated metabolic pathways may offer novel perspectives on the pathophysiology of SSNHL, presenting potential targets for future therapeutic interventions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2025.1567064","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T04:10:16Z","timestamp":1752466216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Untargeted plasma metabolite detection in sudden sensorineural hearing loss: identifying key metabolic signatures"],"prefix":"10.3389","volume":"12","author":[{"given":"Rongyue","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangruici","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohang","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.3390\/nu15112552","article-title":"Targeting anti-inflammatory pathways to treat diabetes-induced neuropathy by 6-hydroxyflavanone","volume":"15","author":"Akbar","year":"2023","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1194\/jlr.M800174-JLR200","article-title":"A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma","volume":"49","author":"Bergmark","year":"2008","journal-title":"J. lipid Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/jbt.10069","article-title":"Hepatoprotection by L\u2010cysteine\u2010glutathione mixed disulfide, a sulfhydryl\u2010modified prodrug of glutathione","volume":"17","author":"Berkeley","year":"2003","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3390\/metabo12030214","article-title":"Metabolomic studies in inner ear pathologies","volume":"12","author":"Boullaud","year":"2022","journal-title":"Metabolites"},{"key":"B5","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1097\/00005537-200305000-00006","article-title":"Clinical associations of serum antiendothelial cell antibodies in patients with sudden sensorineural hearing loss","volume":"113","author":"Cadoni","year":"2003","journal-title":"Laryngoscope"},{"key":"B6","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.jacc.2006.11.054","article-title":"Phosphorylcholine-targeting immunization reduces atherosclerosis","volume":"50","author":"Caligiuri","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1021\/acschemneuro.8b00101","article-title":"Dark classics in chemical neuroscience: N, N-dimethyltryptamine (DMT)","volume":"9","author":"Cameron","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1177\/000348940911800308","article-title":"Prothrombotic gene mutations in patients with sudden sensorineural hearing loss and cardiovascular thrombotic disease","volume":"118","author":"Capaccio","year":"2009","journal-title":"Ann. Otology, Rhinology and Laryngology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.anl.2016.10.003","article-title":"Metabolomic analysis of urine with Nuclear Magnetic Resonance spectroscopy in patients with idiopathic sudden sensorineural hearing loss: a preliminary study","volume":"44","author":"Carta","year":"2017","journal-title":"Auris Nasus Larynx"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/lary.20873","article-title":"Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss","volume":"120","author":"Chau","year":"2010","journal-title":"Laryngoscope"},{"key":"B11","first-page":"443","article-title":"Editorial board of Chinese jour nal of otorhinolaryngology Head and Neck Surgery. Guideline of diagnosis and treatment of sudden deafness","volume":"50","year":"2015","journal-title":"Chin. J. Otorhinolaryngology Head Neck Surg."},{"key":"B12","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/joim.13234","article-title":"Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases","volume":"290","author":"de Vries","year":"2021","journal-title":"J. Intern. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"762092","DOI":"10.1155\/2013\/762092","article-title":"Investigation of the material basis underlying the correlation between presbycusis and kidney deficiency in Traditional Chinese Medicine via GC\/MS metabolomics","volume":"2013","author":"Dong","year":"2013","journal-title":"Evidence\u2010Based Complementary Altern. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"474","DOI":"10.2174\/1573412916666200102112339","article-title":"UPLC-Q-TOF\/MS based untargeted metabolite and lipid analysis on premature ovarian insufficiency plasma samples","volume":"17","author":"F\u0131nd\u0131k","year":"2021","journal-title":"Curr. Pharm. Anal."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e50340","DOI":"10.15252\/embr.202050340","article-title":"Endogenous metabolites promote stress resistance through induction of mitohormesis","volume":"21","author":"Fischer","year":"2020","journal-title":"EMBO Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"720","DOI":"10.3390\/metabo13060720","article-title":"Antibodies against phosphorylcholine\u2014implications for chronic inflammatory diseases","volume":"13","author":"Frosteg\u00e5rd","year":"2023","journal-title":"Metabolites"},{"key":"B17","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.sjbs.2019.10.001","article-title":"Exome sequencing and metabolomic analysis of a chronic kidney disease and hearing loss patient family revealed RMND1 mutation induced sphingolipid metabolism defects","volume":"27","author":"Gaboon","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"B18","volume-title":"Metabolomics shows the way to new discoveries","author":"Goodacre","year":"2005"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1442879","DOI":"10.3389\/fpls.2024.1442879","article-title":"Exploring stachydrine: from natural occurrence to biological activities and metabolic pathways","volume":"15","author":"He","year":"2024","journal-title":"Front. Plant Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1093\/oxfordjournals.jbchem.a021865","article-title":"Functional roles of sphingosine, sphingosine 1-phosphate, and methylsphingosines: in regard to membrane sphingolipid signaling pathways","volume":"122","author":"Igarashi","year":"1997","journal-title":"J. Biochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.advms.2019.05.003","article-title":"Effect of quinolinic acid\u2013a uremic toxin from tryptophan metabolism\u2013on hemostatic profile in rat and mouse thrombosis models","volume":"64","author":"Leszczy\u0144ska","year":"2019","journal-title":"Adv. Med. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.3390\/molecules24173049","article-title":"Position impact of hydroxy groups on spectral, acid\u2013base profiles and DNA interactions of several monohydroxy flavanones","volume":"24","author":"\u0141odyga-Chru\u015bci\u0144ska","year":"2019","journal-title":"Molecules"},{"key":"B23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.3389\/fimmu.2016.00246","article-title":"Current evidence for a role of the kynurenine pathway of tryptophan metabolism in multiple sclerosis","volume":"7","author":"Lovelace","year":"2016","journal-title":"Front. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"104024","DOI":"10.1155\/2013\/104024","article-title":"Quinolinic acid: an endogenous neurotoxin with multiple targets","volume":"2013","author":"Lugo-Huitr\u00f3n","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"15188","DOI":"10.3390\/ijms242015188","article-title":"A systematic review on metabolomics analysis in hearing impairment: is it a possible tool in understanding auditory pathologies?","volume":"24","author":"Malesci","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/biof.150","article-title":"Ca2+ homeostasis defects and hereditary hearing loss","volume":"37","author":"Mammano","year":"2011","journal-title":"Biofactors"},{"key":"B27","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.heares.2018.05.016","article-title":"Validation of metabolomics analysis of human perilymph fluid using liquid chromatography-mass spectroscopy","volume":"367","author":"Mavel","year":"2018","journal-title":"Hear. Res."},{"key":"B47","article-title":"Metabolomics workbench: an international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools","year":"2016"},{"key":"B28","doi-asserted-by":"publisher","first-page":"68539","DOI":"10.1007\/s11356-021-15468-z","article-title":"Plasma metabolomic profiling in workers with noise-induced hearing loss: a pilot study","volume":"28","author":"Miao","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.cell.2020.02.016","article-title":"A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors","volume":"180","author":"Nemet","year":"2020","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"601","DOI":"10.3109\/00016489409126112","article-title":"Blood viscosity and plasma viscosity in patients with sudden deafness","volume":"114","author":"Ohinata","year":"1994","journal-title":"Acta oto-laryngologica"},{"key":"B31","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1159\/000049069","article-title":"Tryptophan metabolism via the kynurenine pathway in experimental chronic renal failure","volume":"90","author":"Pawlak","year":"2002","journal-title":"Nephron"},{"key":"B32","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.atherosclerosis.2008.10.002","article-title":"Kynurenine, quinolinic acid\u2014the new factors linked to carotid atherosclerosis in patients with end-stage renal disease","volume":"204","author":"Pawlak","year":"","journal-title":"Atherosclerosis"},{"key":"B33","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.thromres.2009.04.011","article-title":"Kynurenines and oxidative status are independently associated with thrombomodulin and von Willebrand factor levels in patients with end-stage renal disease","volume":"124","author":"Pawlak","year":"","journal-title":"Thrombosis Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1097\/MAO.0b013e318170b650","article-title":"Soluble intercellular adhesion molecule 1 and soluble vascular cell adhesion molecule 1 in sudden hearing loss","volume":"29","author":"Quaranta","year":"2008","journal-title":"Otology and Neurotol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1160\/TH05-08-0554","article-title":"Vascular risk factors in sudden hearing loss","volume":"95","author":"Rudack","year":"2006","journal-title":"Thrombosis haemostasis"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/S0140-6736(09)62071-7","article-title":"Sudden sensorineural hearing loss","volume":"375","author":"Schreiber","year":"2010","journal-title":"Lancet"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.3390\/microorganisms11071825","article-title":"Microbial-derived tryptophan metabolites and their role in neurological disease: anthranilic acid and anthranilic acid derivatives","volume":"11","author":"Shaw","year":"2023","journal-title":"Microorganisms"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00405-017-4768-4","article-title":"Altered auditory and vestibular functioning in individuals with low bone mineral density: a systematic review","volume":"275","author":"Singh","year":"2018","journal-title":"Eur. Archives Oto-Rhino-Laryngology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"279","DOI":"10.2174\/1874467211666180516101111","article-title":"Impact of sphingolipid mediators on the determination of cochlear survival in ototoxicity","volume":"11","author":"Tabuchi","year":"2018","journal-title":"Curr. Mol. Pharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3390\/metabo9110262","article-title":"Relationship between metabolomics profile of perilymph in cochlear-implanted patients and duration of hearing loss","volume":"9","author":"Trinh","year":"2019","journal-title":"Metabolites"},{"key":"B41","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1161\/CIRCULATIONAHA.116.020838","article-title":"Oxidized phospholipids on lipoprotein (a) elicit arterial wall inflammation and an inflammatory monocyte response in humans","volume":"134","author":"van der Valk","year":"2016","journal-title":"Circulation"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1080\/00016489.2017.1325006","article-title":"Cisplatin-induced metabolome changes in serum: an experimental approach to identify markers for ototoxicity","volume":"137","author":"Videhult Pierre","year":"2017","journal-title":"Acta Oto-Laryngologica"},{"key":"B43","doi-asserted-by":"publisher","first-page":"10535","DOI":"10.1039\/d3fo03585a","article-title":"Indole-3-acetamide from gut microbiota activated hepatic AhR and mediated the remission effect of Lactiplantibacillus plantarum P101 on alcoholic liver injury in mice","volume":"14","author":"Wang","year":"2023","journal-title":"Food and Funct."},{"key":"B44","doi-asserted-by":"publisher","first-page":"982561","DOI":"10.3389\/fmolb.2022.982561","article-title":"Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s10020-018-0010-0","article-title":"Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction induced by homocysteine","volume":"24","author":"Xie","year":"2018","journal-title":"Mol. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"D389","DOI":"10.1093\/nar\/gkaa1009","article-title":"OrthoDB in 2020: evolutionary and functional annotations of orthologs","volume":"49","author":"Zdobnov","year":"2021","journal-title":"Nucleic acids Res."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1567064\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T04:10:18Z","timestamp":1752466218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1567064\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":47,"alternative-id":["10.3389\/fmolb.2025.1567064"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2025.1567064","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]},"article-number":"1567064"}}