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.