Abstract

Dental caries is a highly prevalent disease involving complex local immune alterations that contribute to its progression and resolution. The objective of this study was to evaluate the effect of dental treatment on the salivary immunoproteome in individuals with dental caries using a longitudinal, group-level proteomic approach based on biological pooling, and to descriptively explore associated changes in salivary bacterial composition. Stimulated and unstimulated saliva samples were collected from 46 participants across three clinical phases: diagnosis, post-non-invasive/microinvasive treatment, and post-invasive/restorative treatment. Proteomic profiling was performed using nLC-MS/MS, while salivary bacterial composition was assessed descriptively by MALDI-TOF MS-based identification. Data analysis included functional enrichment and pathway-level characterization. The results indicate a progressive normalization of several immune-related pathways following treatment, whereas neutrophil degranulation remained active with a reconfigured protein composition. Nine proteins, including secretory leukocyte protease inhibitor (SLPI) and mucin 7 (MUC7), remained differentially abundant across all clinical phases, defining a stable immunoproteomic pattern associated with caries susceptibility. Overall, these findings indicate that dental treatment modulates the salivary immunoproteome and highlight persistent immune features that may reflect a post-treatment adaptive state, supporting the relevance of the SLPI-MUC7 axis as a potential indicator of host susceptibility to dental caries.