AbstractAimThis study aimed to characterize the salivary proteome during the induction and resolution of gingival inflammation in the course of human experimental gingivitis (EG), and to cluster the proteomic profiles based on the clinically defined “slow” and “fast” response patterns.Materials and MethodsA total of 50 unstimulated whole saliva were obtained from the EG model which was induced over 21 days (days 0, 7, 14 and 21), followed by a two‐week resolution phase (day 35). Label‐free quantitative proteomics using liquid chromatography–tandem mass spectrometry was applied. Regulated proteins were subject to Gene Ontology enrichment analysis.ResultsA total of 804 human proteins were quantified by ≥ 2 peptides. Principal component analysis depicted significant differences between “fast” and “slow” responders. Despite gingival and plaque scores being similar at baseline among the two groups, “fast” responders presented with 48 proteins that were at > 4‐fold higher levels than “slow” responders. These up‐regulated proteins showed enrichment in “antigen presentation” and “proteolysis.”ConclusionsTogether, these findings highlight the utility of integrative systems‐level quantitative proteomic approaches to unravel the molecular basis of “salivary proteotypes” associated with gingivitis dubbed as “fast” and “slow” responders. Hence, these differential responses may help prognosticate individual susceptibility to gingival inflammation.