Therapeutic Music as a Neuroimmune–Metabolic Modulator in NAFLD: A Spleen‑Centered Working Hypothesis

Abstract

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease, is frequently accompanied by depression and chronic psychological stress that can worsen metabolic dysfunction, promoting NAFLD progression. Given the current limitations of pharmacological treatments for NAFLD, specifically their high cost, potential for adverse side effects, and the lack of long-term data, there is an urgent clinical need for accessible, safe, and cost-effective interventions. Therapeutic music functions as a non-invasive neurocognitive intervention capable of attenuating hypothalamic-pituitary-adrenal axis hyperactivation, restoring parasympathetic tone, and rebalancing immune regulation. These neural and endocrine pathways converge directly on the spleen, a critical immunometabolic nexus translating neuroautonomic signals into systemic inflammatory outputs. Structurally predictable and emotionally engaging acoustic stimuli, such as compositions reminiscent of The Beatles, optimize dopaminergic circuit engagement and alleviate affect-driven inflammatory amplification. This review provides an exploratory, hypothesis-generating delineation of the molecular and physiological networks through which targeted music therapy modulates splenic function. Music therapy emerges not as an ancillary wellness tool, but as a mechanistically grounded intervention at the intersection of neuroimmunology, metabolic medicine, and hepatology, warranting rigorous evaluation in controlled trials.