Identification of metabolic changes in gingivitis using NMR spectroscopy

Objectives: The aim of this study was to identify and quantify candidate metabolic markers of gingivitis in the biofluids of human patients. Methods: Eight systemically healthy, non-smoking females with no history of periodontal disease were examined to determine their oral and systemic response to gingival inflammation using an established model of experimental gingivitis. Plasma and saliva were collected from the subjects before, during and after resolution of gingival inflammation. Samples were analysed using NMR spectroscopy to determine the metabolic components. This data was analysed to identify the metabolic profile of gingival inflammation and to identify metabolites which may be useful as biomarkers of gingival inflammation. Results: Over 75% of metabolites within the plasma and saliva samples have been identified (52 metabolites in saliva and 48 metabolites in plasma). A clear metabolic difference has been found between baseline, gingivitis and resolution samples. The variance between visits was due to a change in concentration of proline, glycine, ornithine, lactate and an unknown metabolite in the saliva samples, and glucose, gluconate, isoleucine and an unknown fatty acid in plasma. Conclusions: In this study we found that the metabolic differences between states of gingival health and gingival inflammation were due to the change in concentration of a number of identified metabolites. For the saliva samples, oral bacteria are likely to contribute to these metabolic differences. At resolution of disease, despite appearing clinically healthy, subjects had a different metabolome to gingival health at baseline, indicating that there is still underlying inflammatory activity occurring in the gingival tissues. We have also found that the metabolic profile is altered both locally and systemically with gingival inflammation. Identification of the metabolites associated with gingivitis will contribute to an increase in understanding of the pathogenesis of gingivitis. Further studies should investigate metabolomic changes in periodontitis.