Mass spectrometry-based metabolomic profiling identifies alterations in salivary redox status and fatty acid metabolism in response to inflammation and oxidative stress in periodontal disease

Periodontal diseases represent the most common chronic inflammatory diseases in humans and a major cause of tooth loss. Combining mass spectrometry-based ionomics and targeted lipidomics on fatty acid metabolites, we identified significant alterations in redox status and fatty acid metabolism in saliva in response to chronic inflammation and oxidative stress in periodontal disease in a cohort of nonsmoker subjects with chronic periodontitis. For the first time, ionomic profiling of around 30 ions in saliva revealed significantly decreased levels of redox-active metal ions including Mn, Cu, and Zn in the periodontal group, which is consistent with decreased levels of superoxide dismutases in saliva and serum. A targeted lipidomic approach was employed to monitor the major metabolites of arachidonic acid and linoleic acid in saliva. We observed increased levels of cyclooxygenase products including PGE2, PGD2, and PGF2α and TXB2, but decreased level of PGI2 in the periodontal group. A unique pattern of the lipoxygenase products of arachidonic acid and linoleic acid was observed with increased level of 5-HETE but decreased levels of 13-HODE and 9-HODE. Levels of salivary F2-isoprostanes, free radical lipid peroxidation products, and a gold standard for oxidative stress in vivo were also significantly elevated. Taking these data together, our study using multiple powerful omics techniques demonstrates that local redox alteration contributes significantly to periodontitis through the modulation of fatty acid metabolism in response to inflammation and oxidative stress. This study highlights the importance of redox status in periodontitis and provides a rationale for preventing periodontal disease by dietary interventions aiming to restore redox balance.