## 5 Salivary Metabolomics: Techniques and Applications
Such metabolites have a significant correlation with periodontal clinical parameters, being candidates for an accurate diagnosis of the disease. In particular, taurine, isovalerate, butyrate, and glucose augmented significantly in periodontitis patients. An increase in butyrate and isovalerate-major short-chain fatty acids (SCFAs) in periodontitis [30; 40], and, in opposition to the study of Kim et al. [74], demonstrated the existence of the. association of the increase in butyrate with the progress of the periodontitis stage [77; 81]. In fact, SCFAs \begin{table}
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**References** & **Study Design** & **Sample Size** & **Method of Analysis** &
\begin{tabular}{} **Variation in Metabolomic** \\ **Profile** \\ \end{tabular} \\ \hline Aimeti et al. [79] & Cross-sectional study & 32 cases, 22 controls & Nuclear Magnetic Resonance & Higher concentrations of acetate, \(\gamma\)-aminobutyrate, \(n\)-butyrate, succinate, trimethylamine, propionate, phenylalanine, and valine, and decreased concentrations of pyruvate and \(N\)-acetyl in GCP patients compared with controls. \\ Rzeznic et al. [42] & Cross-sectional study & 26 cases, 25 controls & Nuclear Magnetic Resonance & Higher concentrations of lactate, \(\gamma\)-amino-butyrate, methanol, and threonine in periodontitis. Higher concentrations of pyruvate, \(N\)-acetyl groups, and lactate, and higher levels of proline, phenylalanine, and tyrosine in GCP and GAgP patients compared with controls. \\ Kim et al. [74] & Cross-sectional study & 129 cases, 92 controls. & Nuclear Magnetic Resonance & Higher concentrations of taurine, \(\beta\)-glucose in periodontitis. Higher concentrations of caroten, isocaproate, butyrate, isovalerate, isopropanol, 4-aminobutyrate, choline, sucrose-glucose-lysine, lactate-proline, lactate, and proline in periodontitis. \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Main findings of the studies about metabolomics in periodontitis. are the end-products of bacterial metabolism; they are involved in periodontitis [70] and are associated with deep probing depth, loss of attachment, and bleeding on probing [42]. Moreover, butyrate and isovalerate in high concentrations were found in sites positive to _Porphyromonas gingivalis_, which is one of the most important periodontal bacteria [71]. Periodontal bacteria products induce tissue damage, and for this reason, the host tries to defend itself by metabolite relapse with antioxidant effects, in particular Taurine. Such a metabolite accumulates in damaged tissues to preserve them by its antioxidant effect, maintaining cellular homeostasis under inflammatory conditions [75,76]. The increase in taurine in periodontitis shows its role in tissue protection and repair [82] and its diagnostic importance [74]. The increase in glucose levels demonstrates that the energy demand of pathogenic bacteria was increased and a more favorable energy environment for oral bacteria was generated during periodontitis [74]. Ethanol concentrations decrease significantly in periodontitis patients in comparison with healthy controls [74,82]. This volatile organic compound is present in saliva and is produced by bacterial alcohol dehydrogenase. It can be converted into acetaldehyde, a known carcinogen. The bacterial conversion of ethanol to acetaldehyde in saliva is associated with poor oral health and may play a role in oral cancer development. The fact that a more significant reduction in ethanol concentration was observed in periodontitis patients indicates that ethanol oxidation is highly activated in the presence of periodontitis [74]. The aforementioned metabolites are the results of preliminary research; further investigations are needed. The discoveries should find the most accurate methods of identification of periodontitis-related metabolites to integrate them into daily clinical practice.