Impact of sodium butyrate on stroke-related intestinal injury in diabetic mice: Interference with Caspase-1/GSDMD pyroptosis pathway and preservation of intestinal barrier.

Diabetic stroke-associated acute intestinal injury is characterized by high mortality, disability, and poor prognosis due to the lack of effective therapies. Our prior research demonstrated that administration of 300 mg/kg sodium butyrate (NaB) can improve neurological outcomes post-diabetic stroke. Nonetheless, whether the effect of NaB is related to intestinal regulation, along with its underlying mechanisms, remains uncertain. This study aims to investigate the effects and mechanistic pathways of NaB on diabetic stroke-associated acute intestinal injury. A middle cerebral artery occlusion/reperfusion model was established in mice with streptozotocin-induced diabetes. The results demonstrated that NaB alleviated colonic injury 24 h after reperfusion in diabetic stroke. Pyroptosis-related protein levels in colonic tissues were significantly elevated following diabetic stroke but were markedly reduced with NaB treatment. NaB also improved gut barrier integrity and reduced inflammation, promoting epithelial barrier self-repair. In the NaB combined with lipopolysaccharide group, lipopolysaccharide administration induced a significant inflammatory response in the colonic tissue. Conversely, treatment with NaB and VX-765 (an inhibitor for Caspase-1) led to a notable alleviation in intestinal inflammation. These findings suggest that NaB mitigates colonic injury and enhances barrier function following diabetic stroke, potentially through the Caspase-1/Gasdermin D pyroptosis pathway. This study may provide a novel strategy and direction for intestinal rehabilitation in diabetic stroke patients.