Transcranial ultrasound stimulation ameliorates dextran sulphate sodium-induced colitis and behavioural disorders by suppressing the inflammatory response in the brain

Inflammatory bowel disease (IBD) is associated with neuroinflammation, which may contribute to an increased risk of neurodegenerative disorders. This research investigated the potential of transcranial low-intensity pulsed ultrasound (LIPUS) to mitigate colonic inflammation induced by dextran sulphate sodium (DSS), focusing on its effects via the brain-gut axis. Colitis and neuroinflammation were induced in mice by administering 3% (wt/vol) DSS for 7 days. Subsequently, the brain was subjected to LIPUS stimulation at intensities of 0.5 or 1.0 W/cm² for 3 days. Biological samples were analyzed using real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and histological observation. Behavioural dysfunctions were assessed using the open field test, novel object recognition task, and Y-maze test. The alteration in gut microbiota composition was assessed through 16S rRNA sequencing. LIPUS therapy notably alleviated colitis symptoms and suppressed inflammation in both the colon and hippocampus of DSS-exposed mice. Compared with the group treated only with DSS, the LIPUS treatment showed decreased crypt destruction and partial epithelial barrier preservation. Moreover, LIPUS preserved intestinal barrier function by upregulating the levels of occludin and zonula occludens, decreasing the levels of lipopolysaccharide (LPS) and LPS-binding protein in serum, and ameliorating behavioural disorders. Further analysis indicated that LIPUS did not significantly transform the composition of the intestinal microbiota, but the microbial community showed some differences from the community in the DSS-only treatment group. This study demonstrates that transcranial LIPUS stimulation could be a novel therapeutic strategy for IBD and neuroinflammation via regulation of inflammatory interactions across brain-gut axis.