Abstract

Objective: This observational, cross-sectional, and analytical study aimed to explore the pathophysiological mechanisms of gingivitis in pregnancy by analyzing the salivary proteomic profile according to gingival bleeding status. Materials and Methods: Pregnant women at the 27th week of gestation or beyond were categorized into two groups: those with excessive gingival bleeding on probing (BOP > 50%; G1) and those without generalized gingivitis (BOP < 30%; G2). A comprehensive full-mouth periodontal examination was performed. Unstimulated whole-mouth saliva samples were collected and individually processed using Nano Liquid Chromatography Electron Spray Ionization Tandem Mass Spectrometry (nLC-ESI-MS/MS). Results: Proteomic analysis identified 187 salivary proteins, with 75 shared between groups. Sixty proteins were upregulated and seven were downregulated in G1. The most upregulated were Protein S100-A9 (16-fold), Neutrophil Defensins 1 and 3 (7-fold), Protein S100-A8 (5-fold), Beta-2-Microglobulin (4-fold), and multiple immunoglobulin isoforms. Histatin-3 was the only protein downregulated by more than 2-fold. Gene Ontology analysis revealed significant enrichment in processes related to antimicrobial humoral response, bacterial defense mechanisms, and immune regulation, reflecting the inflammatory state. Conclusion: These findings provide insights into the salivary proteomic alterations associated with generalized gingivitis in pregnancy, particularly highlighting immune and antimicrobial pathways linked to excessive gingival inflammation. © 2025 The Author(s). Oral Diseases published by John Wiley & Sons Ltd.