Stellate ganglion block attenuates gut barrier injury in sleep-deprived rats in a gut microbiota-dependent manner

Patients with sleep disorders often suffer from gastrointestinal diseases such as abdominal pain and diarrhea, which severely affect their quality of life. Therefore, identifying interventions to mitigate sleep deprivation (SD)-induced intestinal barrier damage is an important clinical objective. The potential of stellate ganglion block (SGB) to improve gut health in this context and its underlying mechanisms remain unclear. In phase one, rats were randomly allocated to CON, SD1, SD3, SD5, and SD7 groups (n = 4–6 per group), undergoing SD for 0, 1, 3, 5, or 7 days respectively. The time point of peak intestinal injury was determined by Evans blue staining. Based on these results, a second phase assigned rats to six groups (n = 5–6 per group): CON, SD, SD + SGB, antibiotics (ABX), ABX + SD, and ABX + SD + SGB. Intestinal barrier function was assessed via crypt depth, mucosal thickness, and expression of tight junction proteins (Occludin, ZO-1). Gut microbiota composition was analyzed by 16S rRNA gene sequencing, and microbial metabolites were profiled using LC–MS-based non-targeted metabolomics. Evans blue staining showed that intestinal permeability was significantly increased after 7 days of SD, reaching approximately fourfold higher levels compared with the control (CON) group ( p < 0.0001). Consistent with this functional impairment, morphological analysis revealed that the SD group exhibited substantial reductions in crypt depth (by ~ 56%), mucosal thickness (by ~ 59%), and goblet cell count (by ~ 45%) relative to CON (all p < 0.01). Treatment with SGB markedly attenuated these alterations, restoring mucosal thickness and goblet cell count to about 78% and 97% of the CON levels, respectively. At the molecular level, the expression of the tight junction protein Occludin, which was significantly lower in the SD group (~ 38% of CON, p < 0.05), was also recovered after SGB intervention. Notably, the therapeutic effects of SGB were absent in pseudo-germ-free conditions, suggesting a microbiota-dependent mechanism. 16S rRNA gene sequencing confirmed that SGB altered the gut microbiota composition. Furthermore, untargeted metabolomics revealed that SGB counteracted SD-induced shifts in the fecal metabolome, specifically altering the relative abundance of metabolites associated with inflammatory lipids and microbial amino acid metabolism. SGB was associated with the attenuation of SD-induced intestinal barrier dysfunction, and this effect was absent under antibiotic treatment, suggesting a microbiota-dependent component. These findings offer theoretical support for its clinical application.