Dynamic changes in neutrophil activation and metabolic profile during pregnancy are associated with gingival inflammation

Abstract

Neutrophils are key players in both periodontal and placental immunity, undergoing profound immunometabolic and functional changes during pregnancy. Their excessive activation has been linked to gestational complications. Gingivitis, and even more so periodontitis, the advanced stage of this condition, are chronic inflammatory diseases that frequently worsen during pregnancy and have been associated with adverse outcomes such as fetal growth restriction and placental dysfunction. Although bacterial dissemination and inflammation are thought to mediate this link, the underlying mechanisms remain poorly understood. How neutrophil activation and metabolism evolve throughout pregnancy?and how this relates to the exacerbation of periodontal inflammation?remains largely unexplored. We analyzed the immunometabolic and activation profiles of circulating neutrophils from pregnant women at 16?20 weeks and term, alongside their gingival inflammatory status. Our findings show that pregnancy reprograms neutrophil metabolism, promoting a progressive shift towards enhanced glucose utilization and increased lipid droplet accumulation at term. Basal reactive oxygen species production increased throughout pregnancy and correlated with gingival inflammation. Basal and PMA-induced neutrophil extracellular trap release also increased with gestation. Gingival crevicular fluid samples further stimulated neutrophil activation, particularly those enriched in P. gingivalis. These results reveal a dynamic immunometabolic rewiring in maternal circulating neutrophils throughout pregnancy, suggesting its modulatory role in the interplay between systemic immunity and oral inflammation.