# Acute High-Intensity Noise Exposure Induces Cognitive Impairment and Arachidonic Acid Metabolism-Related Molecular Alterations in Rats: A Multi-Omics Study

## TL;DR

Exposure to loud noise harms rat cognition and disrupts brain and gut metabolism, with arachidonic acid playing a central role.

## Contribution

This study reveals a coordinated microbiota-lipid-protein network linking noise-induced cognitive impairment to arachidonic acid metabolism.

## Key findings

- Acute noise exposure reduced cognitive performance and caused hippocampal damage in rats.
- Arachidonic acid-derived metabolites were consistently downregulated across multiple omics layers.
- A critical response window was identified at 7 days post-exposure with gut microbiota and metabolic changes.

## Abstract

Background: Acute high-intensity noise exposure represents a critical environmental stressor; however, its impact on brain function and the underlying mechanisms remain incompletely understood. This study aimed to investigate the effects of acute high-intensity noise exposure on cognitive function in rats, utilizing multi-omics analysis to explore potential mechanisms. Methods: Rats were exposed to acute noise at 120 dB, and brain function was evaluated using the novel object recognition (NOR) test, recordings of electroencephalographic activity, and histopathological examination. Longitudinal serum metabolomics and fecal metagenomics were performed on samples collected at 0 h, 7, 14, and 28 days post-exposure. Quantitative profiling of oxylipins and proteomics were conducted at a critical time point, followed by integrative multi-omics network analysis. Results: Acute high-intensity noise exposure significantly reduced the recognition index in the NOR test, increased theta-band power, and induced hippocampal neuronal damage. Multi-omics analyses revealed time-dependent alterations in gut microbiota and metabolic profiles, identifying day 7 as the critical response window, with arachidonic acid (AA)-derived metabolites consistently downregulated across omics layers. Integrated analysis revealed a coordinated microbiota–oxylipins–proteins network, highlighting key AA-derived oxylipins (e.g., 8-HETE, 12-HETE) that correlated with specific gut microbiota and proteins involved in lipid metabolism and inflammation. Conclusions: Acute high-intensity noise exposure induces cognitive impairment and systemic molecular disturbances. AA-centered lipid metabolism acts as a key hub linking gut microbiota dysbiosis with inflammatory and metabolic protein alterations, providing multi-omics evidence for coordinated microbiota–lipid–protein dysregulation underlying noise-induced neurobiological dysfunction.