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Metabolomic signatures of periodontal health and disease
Thesis

Metabolomic signatures of periodontal health and disease

Umar Hayat Salman
University of Iowa
Master of Science (MS), University of Iowa
Spring 2026
DOI: 10.25820/etd.008477
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Metabolomic Signatures of Periodontal Health and Disease_Umar1.13 MB
Embargoed Access, Embargo ends: 06/29/2028

Abstract

Metabolomic Signatures of Periodontal Health and Disease Background: Periodontal disease is a multifactorial inflammatory condition driven by complex interactions between the subgingival microbiome and the host immune response. While advances in microbiome and genomic research have improved our understanding of disease etiology, these approaches do not fully capture the functional biochemical state of periodontal tissues. Metabolomics provides a dynamic representation of ongoing biological processes and may offer clinically relevant biomarkers. However, limited studies have simultaneously evaluated metabolomic profiles across both site-specific and whole-mouth oral biofluids. Objective: The aim of this study was to characterize and compare metabolomic profiles of saliva and gingival crevicular fluid (GCF) in periodontal health and disease, and to identify metabolic signatures associated with periodontal inflammation. Methods: This cross-sectional study included systemically healthy or medically controlled individuals diagnosed with Stage III or IV periodontitis, along with periodontally healthy controls. Unstimulated saliva and GCF samples (from shallow and deep periodontal sites) were collected and analyzed using gas chromatography–mass spectrometry (GC/MS) and liquid chromatography–mass spectrometry (LC/MS). Metabolomic data were processed and analyzed using MetaboAnalyst 6.0. Sparse partial least squares discriminant analysis (sPLS-DA), pathway enrichment analysis, and network-based approaches were used to identify discriminatory metabolites and biological pathways. Results: Distinct metabolomic profiles were observed between saliva and GCF, even under healthy conditions, indicating that these biofluids represent biologically different environments. In periodontal disease, GCF from deep sites exhibited the most pronounced metabolic alterations, forming a distinct cluster separate from shallow sites and saliva. Key metabolic changes were associated with glycolysis, the tricarboxylic acid (TCA) cycle, amino acid metabolism, and oxidative stress pathways. Combined analysis demonstrated that biofluid type was the primary driver of metabolomic variation, while disease status contributed additional stratification, particularly within GCF samples. Conclusions: This study demonstrates that periodontal disease is associated with site-specific metabolic reprogramming, with GCF serving as a sensitive indicator of localized disease activity. In contrast, saliva reflects a broader, less specific metabolic profile. These findings highlight the importance of biofluid selection in metabolomic studies and support the potential of metabolomics for identifying clinically relevant biomarkers for periodontal disease.

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