Abstract
BACKGROUND: Gastrointestinal dysfunction is a common and detrimental complication following stroke, closely linked to poor outcomes. Emerging evidence implicates gut microbiota dysbiosis and intestinal barrier disruption in this process. This study investigated whether exercise preconditioning (EP) could protect against post-stroke gastrointestinal impairment and elucidated the underlying mechanisms involving the gut microbiota-intestine axis. METHODS: A meta-analysis was conducted to estimate the global incidence of post-stroke constipation. In vivo, Sprague-Dawley rats underwent 2 weeks of treadmill-based EP prior to transient middle cerebral artery occlusion (tMCAO). Neurological deficits, fecal properties, gut microbiota composition (16S rRNA sequencing), intestinal permeability, and mucosal inflammation were systematically evaluated. RESULTS: Meta-analysis revealed a 40% pooled incidence of post-stroke constipation. In the tMCAO model, EP significantly improved neurological scores and alleviated constipation, as evidenced by increased fecal water content and motility. EP restored gut microbiota diversity, enriched beneficial taxa (e.g., Lactobacillus), and reduced opportunistic pathogens. Furthermore, EP attenuated intestinal barrier disruption-marked by upregulated tight junction proteins (ZO-1, occludin)-and suppressed colonic inflammation (reduced TNF-α and IL-6). CONCLUSION: Exercise preconditioning mitigates post-stroke gastrointestinal dysfunction, which is associated with preserving gut microbiota homeostasis, reinforcing the intestinal epithelial barrier, and dampening local inflammation. These findings highlight EP as a promising non-pharmacological strategy to improve systemic resilience and outcomes after stroke through gut-targeted mechanisms.