Metabolite identification was conducted by matching detected features based on accurate mass retention time and fragmentation spectra against reference libraries. Liquid chromatography derived metabolites were annotated using Progenesis QI with consideration of mass accuracy isotope patterns and MS MS spectral similarity. Gas chromatography derived metabolites were identified using MS DIAL through comparison with commercial and in house electron impact spectral libraries. Internal standards were used to monitor analytical performance and normalization quality. Only metabolites meeting predefined confidence thresholds were retained for statistical analysis and biological interpretation.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - negative - reverse-phase","Liquid Chromatography MS - positive - reverse-phase","Gas Chromatography MS -"],"chromatography_protocol":["Liquid chromatography was performed using a Waters ACQUITY UPLC I Class Plus system equipped with an HSS T3 reverse phase column with dimensions of 100 mm by 2.1 mm and particle size of 1.8 um. The column temperature was maintained at 45 degrees Celsius. Mobile phase A consisted of water containing 0.1 percent formic acid and mobile phase B consisted of acetonitrile. A gradient elution was applied starting at 2 percent B for 1 minute followed by an increase to 98 percent B from 1 to 10 minutes and re equilibration to 2 percent B until 15 minutes. The flow rate was 0.35 mL per minute and the injection volume was 3 uL. Gas chromatography was carried out on an Agilent 7890B system using a DB 5MS capillary column with dimensions of 30 m by 0.25 mm by 0.25 um. The oven temperature program started at 60 degrees Celsius with a 0.5 minute hold followed by stepwise increases to a final temperature of 305 degrees Celsius with a 5 minute hold.
"],"publication":["Exploratory metabolomic profiling in migraine with PFO: dysregulated pathways and potential biomarkers."],"submitter_affiliation":["Department of Cardiology, Sichuan Provincial Peopleâs Hospital, School of Medicine, University of Electronic Science and Technology of China"],"submitter_name":["CONG LU"],"organism_part":["blood plasma"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Plasma samples were prepared using a solvent based protein precipitation protocol. Aliquots of 150 uL plasma were extracted with a methanol and acetonitrile mixture at a 2 to 1 volume ratio containing internal standards including acetyl d3 carnitine and phenylalanine d2. The solvent to sample ratio was maintained at 4 to 1. Samples were vortex mixed for 10 minutes at 4 degrees Celsius and subjected to overnight protein precipitation at minus 40 degrees Celsius. After precipitation samples were centrifuged at 12000 g for 10 minutes at 4 degrees Celsius. The supernatants were filtered through 0.22 um organic phase syringe filters prior to analysis. For gas chromatography analysis the dried extracts were derivatized by methoximation using methoxyamine hydrochloride at 37 degrees Celsius for 60 minutes followed by silylation with BSTFA at 70 degrees Celsius for 60 minutes.
"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS13630"],"author":["Lu Cong. University of Electronic Science and Technology of China. lucong100@126.com.","Lu Cong. University of Electronic Science and Technology of China. No. 32 West Section 2, First Ring Road, Qingyang District, Chengdu, Sichuan. lucong100@126.com."],"data_transformation_protocol":["Raw liquid chromatography mass spectrometry data files were processed using Progenesis QI version 3.0 for baseline correction peak picking and retention time alignment. A mass error tolerance of 5 ppm was applied and the maximum retention time shift was set to 0.5 minutes. Features with more than 50 percent missing values per group were removed and annotation scores lower than 36 were excluded. Gas chromatography mass spectrometry data files were converted to ABF format and processed using MS DIAL version 4.8 for spectral deconvolution and library matching against NIST 20 and in house databases. A minimum peak height threshold of 5000 was applied and only annotations with similarity scores of 70 or higher were retained. Data from LC MS positive mode LC MS negative mode and GC MS were integrated into a unified data matrix using in house Python scripts.
"],"study_factor":["Gender","Age"],"submitter_email":["lucong100@126.com"],"sample_collection_protocol":["Venous and arterial blood samples were collected from PFO-M using heparin-coated vacutainer tubes, while the healthy controls provided venous blood only. All participants underwent fasting overnight (more than 12 hours) prior to morning phlebotomy to minimize circadian and dietary confounding. Blood samples were centrifuged at 1000 g for 10 minutes at 4 C within 1 hour post-collection to separate cellular components, and the supernatant was further centrifuged at 16,000 g for 10 minutes at 4 C to remove residual platelets and microparticles. The final plasma supernatant was stored at -80 C until further analysis.
"],"omics_type":["Metabolomics"],"study_design":["tryptophan metabolism","Neurosteroids","Migraine","indoleacrylic acid","Patent foramen ovale"],"curator_keywords":["tryptophan metabolism","Neurosteroids","Migraine","indoleacrylic acid","Patent foramen ovale"],"mass_spectrometry_protocol":["Liquid chromatography was coupled to a Thermo Q Exactive HF high resolution mass spectrometer operated in both positive and negative ionization modes. Full scan mass spectra were acquired over a mass to charge range from 70 to 1050 with a resolving power of 15000. Data dependent tandem mass spectrometry was performed using a top ten acquisition method with stepped normalized collision energies of 10 20 and 40. Gas chromatography was coupled to an Agilent 5977A mass selective detector operated under electron impact ionization at an ionization energy of 70 eV. The ion source temperature was set to 230 degrees Celsius and the quadrupole temperature was set to 150 degrees Celsius. Full scan acquisition was performed over a mass to charge range from 50 to 500.
"],"metabolite_name":["Farnesyl Acetone","Janthitrem C","1-O-(2r-Hydroxy-4z-Pentadecenyl)-Sn-Glycerol","PE(20:4(5Z,8Z,11Z,14Z)/0:0)","2-Tetradecylcyclobutanone","6r,7s-Epoxy-3z,9z-Eicosadiene","Coenzyme Q8","PC(18:1(11Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z))","5alpha-Cholest-22e-En-3beta-Ol","Clausarinol","PC(16:0/20:4(8Z,11Z,14Z,17Z))","PC(P-18:1(11Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z))","PC(20:4(8Z,11Z,14Z,17Z)/18:1(11Z))","2-Hydroxycinnamic Acid","3-Hydroxyoctadecanoylcarnitine","Caffeine","Glycochenodeoxycholic Acid","PI(20:4(5Z,8Z,11Z,14Z)/0:0)","PC(20:4(5Z,8Z,11Z,14Z)/18:1(11Z))","Dirithromycin","PC(20:3(5Z,8Z,11Z)/P-18:1(11Z))","Porson","Indoleacrylic Acid","Palmitoleoyl-Ea","1-(5-Fluoropentyl)-3-(2-Iodobenzoyl)Indole","8e,10e-Tetradecadien-1-Ol","4-[(2,4-Dihydroxyphenyl)Azo]Benzenesulfonic Acid","PnC(16:0/18:1(9Z))","2-(5,8-Tetradecadienyl)Cyclobutanone","6,11-Hexadecadienal","Termitomycesphin C","17-Hydroxy Stearic Acid","Oxotremorine","PC(18:0/20:4(5Z,8Z,11Z,14Z))","Berkeleylactone G","5-(1-Hydroxypropan-2-Yl)Isolongifol-4-Ene","PE(22:5(7Z,10Z,13Z,16Z,19Z)/0:0)","Salvianolic Acid D","6-[1]-Ladderane Hexanol","PC(14:0/20:0)","8,11-Heptadecadienal","PC(16:0/18:2(10E,12Z))","Cis-5-Tetradecenoylcarnitine","Palmitamide","PC(P-16:0/16:0)","PC(16:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))","PC(20:4(8Z,11Z,14Z,17Z)/P-18:0)","PC(18:0/22:4(7Z,10Z,13Z,16Z))","2-Aminoethyl Oleate","Glycocholic Acid","PC(18:0/20:5(5Z,8Z,11Z,14Z,17Z))","Mg(18:2(9z,12z)/0:0/0:0)[Rac]","PS(O-20:0/17:0)","L-Acetylcarnitine","C16 Sphinganine","PC(20:5(5Z,8Z,11Z,14Z,17Z)/P-18:1(11Z))","PC(O-16:0/0:0)","7z,11z,13e-Hexadecatrienal","Deoxycholic Acid Glycine Conjugate","Linoleyl Hydroxamic Acid","PE-NMe(18:1(9Z)/16:0)","PC(18:0/18:2(10Z,12Z))","PE(18:0/0:0)","SM(d17:1/24:1)","2e,13z-Octadecadienal","Lidocaine","PE(16:0/0:0)","PC(18:1(17Z)/18:1(17Z))","N,N-Diethylglycine"],"additional_accession":[]},"is_claimable":false,"name":"Exploratory metabolomic profiling in migraine with PFO: dysregulated pathways and potential biomarkers","description":"Background: Emerging evidence implicates patent foramen ovale (PFO) as a potential contributor to migraine through paradoxical metabolite shunting, microembolism and hypoxemia. However, systematic characterization of metabolic alterations in migraine patients with PFO (PFO-M) remains unexplored, limiting biomarker discovery and mechanistic insights. This study aimed to delineate metabolomic signatures differentiating PFO-M from healthy controls, with a focus on bridging cardiac structural anomalies with metabolic dysregulation.
Methods: Untargeted metabolomic profiling was performed on plasma from 30 PFO-M patients and 17 age- and sex-matched controls. Validation cohorts from 110 PFO-M and 110 healthy controls were analyzed for indoleacrylic acid (IA) levels using ELISA.
Findings: Untargeted metabolomic analysis revealed that 211 annotated metabolites (of 4,858 total), 13 human KEGG metabolic pathways (of 48 total), and 61 reactome pathways (of 119 total) were significantly changed in the plasma of PFO-M group, as compared to controls, predominantly involving branched-chain amino acids (BCAAs), neurosteroids, and tryptophan derivatives. Spearman correlation analysis between these differential metabolites and migraine symptom severity scores identified 32 metabolites exhibiting significant associations. Notably, 8 metabolites, including IA, acetyl-L-carnitine (ALC), L-cystine, beta-alanine, L-alanine, phenylalanine, 5 alpha-dihydrotestosterone sulfate and 5 alpha-pregnan-3 beta,20 beta-diol 3-sulfate, exhibited reduced plasma levels in PFO-migraine patients and significant symptom correlations. Arterial-venous correlation analysis revealed concordant reductions in IA and ALC, with arterial levels inversely associated with symptom severity. Sex stratification revealed lower IA and ALC levels in female patients, negatively correlating with symptom severity, while reduced 5 alpha-dihydrotestosterone sulfate and dehydroepiandrosterone sulfate (DHEA-S) showed positive correlations. Aura-specific sub-analysis identified elevated 4-hydroxyproline and decreased 2-hydroxybutyric acid, ketoleucine, N,N-diethylglycine and L-isoleucine as potential biomarkers, alongside sex-dependent neurosteroid alterations and diminished IA and ALC. Furthermore, plasma IA levels were validated and exhibited markedly lower in another PFO-M cohorts. The IA combined with hs-CRP achieved superior diagnostic accuracy, with IA reduction linked to female gender, prior cerebral infarction, and migraine severity.
Interpretation: Initial characterization of metabolic alterations in PFO-comorbid migraine suggests potential involvement of BCAA, neurosteroid, and tryptophan pathway disturbances. IA reduction, reflecting gut-brain axis disregulation and impaired inflammatory modulation, potentially serving as both
a stratification biomarker and therapeutic target in PFO-M.
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