Periodontal disease metabolomics signatures from different biofluids: a systematic review

Background Periodontitis is resulted from a complex interaction between genetics and epigenetics, microbial factors, and the host response. Metabolomics analyses reflect both the steady-state physiological equilibrium of cells or organisms as well as their dynamic metabolic responses to environmental stimuli. Aim of review This systematic review of the literature aimed to assess which low molecular weight metabolites are more often found in biological fluids of individuals with periodontitis compared to individuals with gingivitis or periodontal health. Key scientific concepts of review All the included studies employed untargeted analysis. One or more biological fluids were analyzed, including saliva (n = 14), gingival crevicular fluid (n = 6), mouthwash (n = 1), serum (n = 3) and plasma (n = 1). Fifty-six main metabolites related to periodontitis have been identified in at least two independent studies by NMR spectroscopy or MS-based metabolomics. Saliva was the main biological fluid sampled. It is noteworthy that 14 metabolites of the 56 detected were identified as main metabolites in all studies that sampled the saliva. The majority of metabolites found consistently among studies were amino acids, organic acids and derivates: acetate, alanine, butyrate, formate, GABA, lactate, propionate, phenylalanine and valine. They were either up- or down-regulated in the studies or this information was not mentioned. The main metabolic pathway was related to phenylalanine, tyrosine and tryptophan biosynthesis. Metabolites more frequently found in individuals with periodontitis were related to both the host and to microorganism responses. Future studies are needed, and they should follow some methodological standards to facilitate their comparison.