Hearing loss affects 1.5 billion individuals worldwide, among whom approximately 430 million suffer from moderate to profound hearing loss. However, due to a lack of awareness and economic limitations, only 20% of adults who require hearing aids actually have access to them (Mahboubi et al., 2018; Nieman & Oh, 2020). Long-term untreated hearing loss will severely impair speech development and interpersonal communication, leading to a decline in quality of life, social isolation, depression, dementia, and cognitive impairment (Rutherford et al., 2018). Hearing loss is a heterogeneous condition, with otitis media being a common cause in children and presbycusis being the most common in adults (Cunningham & Tucci, 2017). Other causes of hearing loss include noise exposure, ototoxic drugs, genetic factors, and so on (World Report on Hearing, 2021). With the increasing aging population and worsening noise pollution, the incidence of hearing loss is expected to rise. It is estimated that by 2050, approximately 2.45 billion people worldwide will suffer from hearing loss, marking a 56.1% increase compared with 2019("Hearing loss prevalence and years lived with disability, 1990-2019: findings from the Global Burden of Disease Study 2019," 2021). Therefore, efforts should focus on promoting early diagnosis, developing preventive strategies, and identifying new treatment targets to reduce the burden of hearing impairment on society.

Since the late 20th century, omics has emerged as a group of disciplines focusing on comprehensive, systematic, and dynamic analysis of the characteristics of molecules including genes, proteins, and metabolites in living organisms. Metabolomics, a rapidly growing branch of omics, concentrates on investigating the composition and concentration of small-molecule metabolites (e.g., carbohydrates, lipids, amino acids, organic acids, typically with molecular weights below 1,500 Da) within organelles, cells, tissues, or biological fluids. According to the Human Metabolome Database evaluated by 11 November 2018, there are at least 114,100 metabolites in humans (Laíns et al., 2019). Exogenous metabolites are highly diverse, for they depend on factors such as diet, drugs, and gut microbiota. The types of endogenous metabolites are highly conservative across species and individuals, while their concentrations vary significantly (Wishart, 2019). Since metabolites are end products of intracellular gene expression (emphasized in genomics, transcriptomics, and proteomics) and direct responders to extracellular environmental events, metabolomics is the closest to phenotype among omics fields. Integrating genetic and environmental influences, it better reflects an organism's current status (Khoramipour et al., 2022). Through high-throughput and high-sensitivity analytical techniques such as nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), combined with bioinformatics analysis, metabolomics aids in exploring disease mechanisms and biomarkers, as well as constructing diagnostic and prognostic models based on differentially expressed metabolites and metabolic pathways. It has been applied to research in various diseases, including cancer, Alzheimer's disease, rheumatoid arthritis, diabetes, COPD, asthma, and retinal diseases, demonstrating great potential for clinical translation (Arneth et al., 2019; Dasgupta et al., 2023; Laíns et al., 2019; Peña-Bautista et al., 2019; Xu et al., 2022; Yang et al., 2019). Recently, researchers have suggested that metabolomics also shows significant potential for diseases such as hearing loss, beyond just traditional metabolic disorders. In the field of hearing loss research, the metabolomics technique is gradually uncovering its complex pathophysiological mechanisms and exploring predictive biomarkers.

This review summarizes the latest advancements in metabolomics technology applied to the study of different types of hearing loss. Since metabolomics can reflect the results of interactions among multiple environmental factors, this review focuses on several common types of acquired hearing loss for which substantial evidence indicates a close link to metabolic and environmental factors, including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), and sudden sensorineural hearing loss (SSNHL). By exploring the potential value of metabolomics in the diagnosis, treatment, and prognosis assessment of hearing loss, this review aims to highlight the significant contributions of metabolomics to understanding and managing acquired hearing loss.