Hydrogen nanobubble water reduces cochlear inflammation and oxidative stress in noise-induced hearing loss via the gut-inner ear axis.

Environmental noise is a widespread stressor that leads to auditory dysfunction and systemic inflammatory disturbances. Noise-induced hearing loss (NIHL) remains a major environmental health concern, yet effective preventive strategies remain limited. Increasing evidence suggests that environmental stress may disrupt gut microbial balance and promote inflammation that leads to distant organs, including cochlea. Here, we demonstrate that hydrogen nanobubble water (HNW), an improved and stabilized oral formulation of molecular hydrogen, reduces cochlear injury induced by noise exposure. Compared with conventional hydrogen-rich water, HNW improved hydrogen retention and stability. In a mouse model of acoustic trauma, oral HNW attenuated auditory threshold shifts and preserved synaptic structure and auditory nerve fiber organization at the nodes of Ranvier. Noise exposure was associated with altered gut microbial composition and activated NF-κB-mediated inflammatory signaling in both intestinal and cochlear tissues. HNW restored microbial balance and attenuated NF-κB activation, and reduced expression of pro-inflammatory cytokines and intracellular reactive oxygen species. These effects were associated with preservation of blood-labyrinth barrier integrity and stabilization of the cochlear immune microenvironment. Collectively, these findings indicate that gut microbiota-associated pathways are involved in noise-induced hearing loss and emphasize the potential of HNW as a strategy to reduce environmentally induced auditory injury.