Inhibition of NLRP3 Inflammasome Activation by Xylitol Attenuates Fusobacterium nucleatum -Driven Preterm Birth

Preterm birth is closely linked to infection with Fusobacterium nucleatum ( F. nucleatum ), a key pathogen in periodontal inflammation. While xylitol is widely known for its antimicrobial and dietary benefits, its role in preventing pregnancy complications, particularly preterm birth, is not well understood. This study examined the activation of the NLRP3 inflammasome by F. nucleatum and assessed xylitol’s ability to inhibit this process and prevent preterm delivery. Our results demonstrate that xylitol effectively protects pregnant mice from preterm birth by reducing inflammation in the placenta, uterus, and blood, and by suppressing NLRP3 inflammasome activation. Xylitol also exhibited antimicrobial effects against F. nucleatum within the uterine and placental tissues, correlating with decreased inflammasome activity. Notably, IL-1β levels in the placental labyrinth zone were significantly reduced in xylitol-treated, F. nucleatum -infected mice. Furthermore, in THP-1 cells, xylitol inhibited both priming (signal 1) and activation (signal 2) phases of the NLRP3 inflammasome induced by F. nucleatum . These findings highlight xylitol’s potential as a preventive agent against preterm birth through targeted inhibition of NLRP3 inflammasome activation during F. nucleatum infection.