Microbial metabolites in the pathogenesis of periodontal diseases: a narrative review

The purpose of this narrative review is to highlight the importance of microbial metabolites in the pathogenesis of periodontal diseases. These diseases, involving gingivitis and periodontitis are inflammatory conditions initiated and maintained by the polymicrobial dental plaque/biofilm. Gingivitis is a reversible inflammatory condition while periodontitis involves also irreversible destruction of the periodontal tissues including the alveolar bone. The inflammatory response of the host is a natural reaction to the formation of plaque and the continuous release of metabolic waste products. The microorganisms grow in a nutritious and shielded niche in the periodontal pocket, protected from natural cleaning forces such as saliva. It is a paradox that the consequences of the enhanced inflammatory reaction also enable more slow-growing, fastidious, anaerobic bacteria, with often complex metabolic pathways, to colonize and thrive. Based on complex food chains, nutrient networks and bacterial interactions, a diverse microbial community is formed and established in the gingival pocket. This microbiota is dominated by anaerobic, often motile, Gram-negatives with proteolytic metabolism. Although this alternation in bacterial composition often is considered pathologic, it is a natural development that is promoted by ecological factors and not necessarily a true “dysbiosis”. Normal commensals are adapting to the gingival crevice when tooth cleaning procedures are absent. The proteolytic metabolism is highly complex and involves a number of metabolic pathways with production of a cascade of metabolites in an unspecific manner. The metabolites involve short chain fatty acids (SCFAs; formic, acetic, propionic, butyric, and valeric acid), amines (indole, scatole, cadaverine, putrescine, spermine, spermidine) and gases (NH(3), CO, NO, H(2)S, H(2)). A homeostatic condition is often present between the colonizers and the host response, where continuous metabolic fluctuations are balanced by the inflammatory response. While it is well established that the effect of the dental biofilm on the host response and tissue repair is mediated by microbial metabolites, the mechanisms behind the tissue destruction (loss of clinical attachment and bone) are still poorly understood. Studies addressing the functions of the microbiota, the metabolites, and how they interplay with host tissues and cells, are therefore warranted.