Substantial effort has been devoted in explaining and understanding the aetiology of the two major oral diseases, dental caries (DC) and periodontal diseases (PD). Both occur as the result of the metabolic activities of microorganisms within the oral biofilm, host factors and altered salivary ecosystem, that favour the emergence and persistence of a dysbiotic microbiota. Besides, both recognize dental hygiene as the main preventive measure. In DC, overexposure to dietary carbohydrates favour acidogenic and aciduric microorganisms and acidic metabolites. Prolonged and repeated state of acidification cause the progressive demineralization of tooth tissue. Periodontitis is a chronic inflammatory disease affecting tissues that surround and support the teeth; it's characterized by expansion of the microbial biofilm at the gingival margin, where keystones bacteria can orchestrate the inflammatory response. Without treatment, periodontal tissue destruction, bone resorption and tooth loss may ensue. Many metabolites associated with inflammation, oxidative stress, tissue degradation, and bacterial metabolism were found to be significantly elevated in both these diseases. Recently, a common development mechanism has been hypothesized. However, to date there is contradictory evidence about the association between DC and PD. The aim of our research, integrating metagenomics and metabolomics analysis, is to investigate the microbial and metabolites profiles in salivary samples in the co-occurrence of both diseases. For this purpose, salivary samples from 120 subjects grouped into 4 categories (30 with DC; 30 with PD, 30 with both diseases, and 30 healthy controls) will be collected. Results obtained by metagenomic and metabolomics procedures and clinical data, will be integrated by proper bioinformatic analysis, could possibly highlight innovative ecological common feature linking DC and PD, as significant prognostic factors in terms of primary and secondary prevention.
Prevention and early diagnosis of dental caries and periodontitis are open challenges in dentistry. Many analytical techniques have been recently used to determine early markers of periodontitis and caries in saliva samples. It is well known that mucosal microbiota and their metabolites play an important role in the development of different diseases (1,2). This research, for the first time, integrating metagenomics and metabolomics analysis aims to identify interplay between oral microbiota and salivary metabolites in a sample of Italian population with both DC and PD. In particular, salivary metabolites could offer significant information on the complex pathogenic mechanisms of periodontal and minearlized tooth tissues health and disease. Although metabolomics in the periodontal field is limited to diagnostic biomarker detection or preliminary comparative researches, a considerable number of molecules and metabolic pathways detected in saliva were found to be associated with oral disease. Up to date, no single biomarker could be considered specific for the disease; however, the combination of cadaverine, 5-oxoproline and histidine seems promising to increase diagnostic accuracy. Salivary fingerprinting has been found affected by temporal stability and reproducibility, both at circadian level and after oral activities or dental treatment. Currently, it is not known whether the main influence on salivary metabolomics is given by the disease activity and severity or by genetic or epigenetic susceptibility. Here, by a multi-omics analysis, we will deepen our understanding of the communication mechanisms within microbial communities that could link caries and periodontitis, revolutionizing the current strategies in oral disease control, consenting us to develop specific agents that could avoid or disturb microbial communication during disease-associated dysbiotic states. Our project could have clinical implications, in terms of diagnosis, prognosis and response to preventive measures and treatment. Thus, the metabolomics and metagenomics features to be demonstrated with this study could have a possible role as prognostic factors in terms of primary and secondary preventive strategies of the two main oral diseases. Moreover, the findings of our project could be very interesting also in terms of health-economy, for developing effective preventive and therapeutic measures.
References
1) Kong G et al. 2021, Neurobiology of Disease,148.
2) Kayama H and Takeda K. 2020, Eur J Immunol. 50:921-931.