Evidence of Intestinal Barrier Dysfunction in Asymptomatic HIV Infection via the NLRP3/Caspase‐1/GSDMD Pyroptosis Pathway

Intestinal barrier dysfunction is an early pathological feature of HIV infection, but its mechanisms remain unclear. This study explored the NLRP3/Caspase‐1/GSDMD pyroptosis pathway in 20 asymptomatic PLWH and 15 matched controls. Our study found that PLWH exhibited mucosal abnormalities, upregulated NLRP3/Caspase‐1/GSDMD‐NT, reduced Occludin and ZO‐1, and elevated IL‐1β, IL‐18, and LPS; NLRP3 activation correlated negatively with Occludin/ZO‐1 and positively with LPS, while CD4 + T‐cell counts correlated negatively with inflammasome activation. Taken together, these findings indicate that intestinal barrier disruption in asymptomatic HIV infection is linked to NLRP3‐mediated pyroptosis, which may drive early epithelial injury and microbial translocation, offering a potential therapeutic target.