Resveratrol attenuates areca nut extract‐induced chronic colitis by suppressing pyroptosis of intestinal epithelial cells via modulating cGAS/STING signaling

Abstract Areca nut extract (ANE) worsens chronic colitis by disrupting gut barrier integrity; however, the underlying mechanisms remain unclear. In this study, we investigate whether resveratrol (RSV) can protect against ANE‐induced colonic injury by specifically targeting intestinal epithelial pyroptosis through the cGAS/STING signaling pathway. To explore this, chronic colitis mouse models were established through ANE treatment, with or without RSV administration. Disease severity, gut barrier function, inflammatory responses, microbiota composition, and metabolite profiles were comprehensively evaluated. Additionally, pyroptosis and the activation of the cGAS/STING pathway were examined in detail to clarify the potential mechanisms involved. Our results demonstrate that RSV significantly alleviated ANE‐induced colitis in a dose‐dependent manner. This was evidenced by a marked reduction in proinflammatory cytokines and the restoration of gut barrier function. Furthermore, RSV reshaped the gut microbiota composition and elevated levels of beneficial metabolites, such as linoleic acid. Notably, RSV also suppressed epithelial pyroptosis. Transcriptomic analysis further confirmed that RSV inhibited cGAS/STING signaling, thereby linking microbial and metabolic changes to improved mucosal health. In conclusion, RSV protects against ANE‐induced chronic colitis by modulating gut microbiota and metabolites and preserving gut barrier integrity through the inhibition of cGAS/STING‐mediated pyroptosis.