Unveiling the mechanism of abdominal and transcranial ultrasound stimulation against DSS-induced colitis based on proteomic analysis

Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is increasingly recognized for its systemic effects, including neuroinflammation and cognitive deficits mediated through the gut-brain axis. This study investigates the potential mechanisms for treating UC with low-intensity pulsed ultrasound (LIPUS). A murine model of UC was established using 3% dextran sulfate sodium (DSS) in C57BL/6J mice. Disease progression was monitored via the Disease Activity Index (DAI). Histopathological evaluations were conducted using Hematoxylin and Eosin (H&E) staining. To elucidate molecular alterations, hippocampal tissues underwent quantitative proteomic analysis employing high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were identified and analyzed to understand the impact of both abdominal and transcranial LIPUS treatments. Both abdominal and transcranial LIPUS treatments were found to alleviate symptoms of colitis. Proteomic analysis of hippocampal tissues identified five DEPs-REPS1, MYG1, KRT13, SRSF10, and CDC42BPG-whose expression levels were modulated by LIPUS interventions. Notably, REPS1 and MYG1, which were downregulated in UC conditions, showed increased expression following LIPUS treatment. KEGG pathway enrichment analysis revealed that these DEPs are primarily involved in the Ras/MAPK signaling pathways. The modulation of these pathways by LIPUS suggests a mechanism by which it exerts anti-inflammatory effects, potentially restoring metabolic balance and reducing inflammation in both the gut and brain. These findings highlight the role of the gut-brain axis in mediating the beneficial effects of LIPUS and suggest its potential as a non-invasive therapeutic strategy for UC and associated neuroinflammatory conditions.