Harnessing the power of biologic agents on the oral microbiota: a way to promote oral and systemic health?

During the long history of their evolution, higher organisms, including mammals, have learnt to take great advantage from living in close contact with selected populations of microbes.1 By living in close contact, animals and microbes underwent a progressive and mutual co-evolutive process that is believed to be a major driving force in the development of adaptive immunity of vertebrates.2 As a result of this co-evolutive process, humans and other animals are characterized by their own unique microbiomes, each consisting of many hundred species of viruses, bacteria, archaea, fungi, and protozoa, unevenly distributed to colonize the different accessible regions of the body.3 The human microbiome is believed to account for 1-3% of body weight and to comprise more than 100 trillion cells.4 The microbiota is involved in complex host-microbe and microbe-microbe interactions, thus modulating nutrient acquisition, adjusting immune system development and general homeostasis (via epigenetic modifications of host genes5), and playing the role of protective barrier to pathogens.4 When a microbiota undergoes qualitative and quantitative changes with regard to distribution in a site and metabolic activity, this condition is defined dysbiosis and is expected to be associated with local and/ or distant pathologic signs.6 Bacterial products released by a dysbiotic microbiota interact with homeostatic mechanisms of the human host and cooperate to the pathogenesis of major human diseases, including diabetes mellitus, inflammatory bowel syndrome, atherosclerosis, obesity, liver disease, and cancer.4,7 he oral microbiota is the second more abundant and one of the most diverse and unique microbial communities in the human body.8 Although many of the most relevant oral and dental diseases, including caries, periodontal and peri-implant diseases, have been long recognized as of microbial origin, only recently the application of culture independent molecular methods using 16S rRNA gene comparative analyzes enabled us to understand that they are caused by dysbiosis rather than by the action of specific pathogens.9-11 The effects of oral dysbiosis are not limited to oral tissues: periodontal diseases, for example, are among the most common human diseases and their associations with diabetes, cardiovascular disease, metabolic disease and obesity, rheumatoid arthritis, certain cancers, respiratory diseases, and cognitive disorders is now supported by increasing evidence.12 Recent molecular investigations showed that some potentially pathogenic oral bacteria (named pathobionts), as for example Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum, colonize in low numbers the oral cavity of healthy individuals, without alerting sentinel systems of mucosal defences.13,14 Conditions able to disrupt the eubiotic equilibrium promote the overgrowth of pathobionts, which suddenly become pathogens (with support from commensals