OBJECTIVE:To investigate the metabolic pathogenesis in subjects with subjective tinnitus (ST)having kidney deficiency patt (KDP) (ST/KDP) in terms of Traditional Chinese Medicine.METHODS:Three groups of subjects,including healthy individuals,subjects with ST/KDP,and subjects who were healthy initially and then developed ST/KDP one year later (healthy → ST/KDP),were recruited for this study.Serum metabolic profiles of all subjects were analyzed using ultra-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry.The metabolic characteristics of the ST/KDP subjects were determined,and the corresponding biomarkers were predicted.The metabolomics data from the healthy → ST/KDP subjects were collected for further verification.RESULTS:Twelve metabolites in the ST/KDP subjects were different from those of the healthy control subjects.Of these metabolites,according to the prediction,except for octanoic acid,other metabolites might characterize ST/KDR Ten metabolites at the outcome ST/KDP stage were different from those at the initial (control) stage.Through the comparison of these metabolites with the predicted metabolites,five common metabolites,including upregulated glutamate,serotonin,orotic acid and 8-oxoguanine,as well as downregulated taurine,were found.These common metabolites were significantly associated with canonical pathways including calcium signaling,y-aminobutyric acid (GABA) receptor signaling,purine and pyrimidine biosynthesis,taurine biosynthesis,and serotonin receptor signaling.CONCLUSION:The metabolic pathogenesis in ST/KDP subjects was characterized by upregulated glutamate,serotonin,orotic acid and 8-oxoguanine,as well as downregulated taurine,additionally,perturbations of calcium signaling,GABA receptor signaling,purine and pyrimidine biosynthesis,taurine biosynthesis,and serotonin receptor signaling.