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Metabolic Reprogramming Bridges Environmental Exposure and Tinnitus Severity: Evidence from AI-Driven Serum
Tingting Qian1, Ge Wang1, Peifan Li1
1ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, NHC Key Laboratory of Hearing Medicine Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Occupational noise exposure is linked to tinnitus severity through metabolic and immune changes. Key metabolites like gamma-aminobutyric acid (GABA) and sphingolipids may mediate this relationship, offering new intervention targets.
Area of Science:
- Auditory Neuroscience
- Environmental Health
- Metabolomics & Lipidomics
Background:
- Tinnitus is a common auditory disorder with unclear links to environmental factors, hindering diagnosis.
- Objective assessment and intervention for tinnitus remain challenging due to its complex etiology.
Purpose of the Study:
- To investigate the metabolic and immune pathways linking occupational noise exposure to tinnitus severity.
- To identify biomarkers for tinnitus and explore potential mechanistic cascades.
Main Methods:
- Utilized a graded observational cohort with documented occupational noise exposure.
- Integrated serum metabolomics, lipidomics, and immunophenotyping.
- Employed interpretable machine learning and mediation analysis.
Main Results:
- A panel of metabolites (GABA, fumaric acid, sphingolipids) significantly mediated the noise-tinnitus association (92% indirect effect).
- Observed early sphingolipid changes, T helper 1 (Th1)-skewed immunity, and reduced GABA levels.
- Developed a CatBoost model predicting tinnitus severity with 84.8% accuracy.
Conclusions:
- Identified specific biomarkers linking noise exposure to tinnitus via metabolic and immune alterations.
- Hypothesize GABAergic tone and sphingolipid metabolism as key pathways for tinnitus.
- Findings suggest novel avenues for tinnitus research and therapeutic interventions.
