Plasma Metabolomic Profiling in Workers with Noise-induced Hearing Loss: a Pilot Study

Noise-induced hearing loss (NIHL) remains a leading occupational related disease and is a serious public health problem. Hence, the identification of potential biomarkers for NIHL prevention and diagnosis has become an urgent work. To discover potential metabolic biomarkers of NIHL, plasma metabolomics analysis in 62 NIHL patients and 62 normal hearing controls was performed using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF MS). Orthogonal partial least square-discriminant analysis (OPLS-DA) model was applied to distinguish metabolite profile alterations in plasma samples between the two groups. The metabolites with a variable importance of projection (VIP) value > 1 and P value < 0.05 were considered to be potential metabolic biomarkers. KEGG database was performed to explore the involved pathways of potential biomarkers. Three autophagy-related genes (PI3K, AKT, and ATG5) were selected for further verification, and mRNA levels were detected using RT-qPCR analysis. Twenty plasma metabolites with VIP > 1 and P < 0.05 were significantly altered between the two groups. Totally, seven metabolic pathways involving the glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, autophagy pathway, choline metabolism, the alpha-linolenic acid metabolism and linoleic acid metabolism, and retrograde endocannabinoid pathway were significantly related to NIHL. Furthermore, verification by RT-qPCR suggested that the mRNA expression levels of PI3K and AKT along with ATG5 were significantly lower in the NIHL patients compared with controls. In summary, the present study provides the first evidence that the identified aberrantly altered metabolites may be the potentially valuable biomarkers of NIHL for occupational noise-exposed workers. Autophagy signal pathway may be involved in the occurrence and development of NIHL. Moreover, this present study may be helpful to further better understand the metabolic changes in NIHL and be helpful for the understanding of pathogenic mechanism.