During recent years, considerable progress has been made in understanding the etiopathogenesis of periodontitis in its various forms and their interactions with the host. Furthermore, a number of reports have highlighted the importance of oral health and disease in systemic conditions, especially cardiovascular diseases and diabetes. In this regard, research has attempted to explain the role of periodontitis in promoting alteration in distant sites and organs. Recently, DNA sequencing studies have revealed how oral infections can occur in distant sites such as the colon, reproductive tissues, metabolic diseases, and atheromas. The objective of this review is to describe and update the emerging evidence and knowledge regarding the association between periodontitis and systemic disease and to analyse the evidence that has reported periodontitis as a risk factor for the development of various forms of systemic diseases in order to provide a better understanding of the possible shared etiopathogenetic pathways between periodontitis and the different forms of systemic diseases.

Background and objectives: In recent years, many different culture-independent molecular techniques have been developed with the aim of investigating the not yet cultivated part of the resident flora of the oral cavity and of analyzing the peri-implant and periodontal flora both in healthy and diseased sites. The most used technologies are Roche 454 pyrosequencing, Illumina HiSeq/MiSeq, ABI SOLiD and Ion Torrent. Due to these methods, two different approaches are available: Metagenomics and the 16S gene analysis. A complementary strategy was also recently developed: Culturomics. Culturomics consists of different culture conditions that allow a very rapid bacterial identification. The focused question of this review was developed in PICO format in order to investigate the role of metagenomics, 16S gene analysis and culturomics (interventions) in the differential study (comparison) of the peri-implant and periodontal microbiome (outcome) in humans (participants). The secondary aim was the characterization of currents limits and future applications of the three techniques. Methods: The authors performed a literature search on three databases (Web of Science, Scopus and PubMed) from 01/01/2003 to 31/06/2019. Date of last search was: 25/08/19. Any type of article dealing with the analysis of periodontal and peri-implant flora with metagenomic, culturomic or 16S gene analysis was included. No language restrictions were applied. Risk of bias for RCT was assessed using the Cochrane collaboration’s tool whereas case-control and cohort studies were evaluated through the Newcastle–Ottawa scale. Results: The initial search resulted in 330 titles in total. After careful evaluation of all results no studies were found to satisfy the primary outcome of the present review. Hence a narrative review dealing with the secondary aim was performed. Conclusions: Metagenomic and 16S gene analysis approaches contributed in clarifying some crucial aspects of the oral microbiome. Based on the reported evidence some bacteria could be found around teeth and implants even in the absence of signs of inflammation and other species are more frequently found in supragingival peri-implant biofilm. Teeth and implants (even if adjacent) seem not to share the same microbiome and healthy teeth have a more diversified one. The same analyses also highlighted that the oral biofilm of smokers is composed by more periodontopathogen bacteria compared to non-smokers and that geographical location and ethnicity seem to play a role in bacterial composition. Culturomics, which has not yet been applied to the study of oral microbiota, consists of the use of different culture conditions and of the identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI–TOF MS) with the aim of increasing the bacterial repertoire and avoiding the limits of molecular methods. In order to better evaluate perspectives and limits of the all presented approaches further studies comparing the different molecular techniques are encouraged. This review received no funding.

The aim of the present study was to investigate the association and impact of periodontitis and tooth loss on a subtype of endothelial progenitor cell (EPC) levels (CD133⁺/KDR⁺). Furthermore, the objective was to determine if the periodontal status influenced CD133⁺/KDR⁺ levels. In all, 88 patients with periodontitis and 79 healthy controls (HCs) were enrolled in the study. Enrolled patients were examined and characterized by clinical and blood sample analysis. Spearman’s correlation test was applied in order to assess the interdependence between CD133⁺/KDR⁺ levels and all periodontal parameters. In order to estimate a statistically significant trend (p-trend) for ordered CD133++/KDR+ quartiles, the Jonckheere–Terpstra test was applied for all variables. Patients in the periodontitis group presented significantly lower CD133⁺/KDR⁺ levels (66.4 (45.5–269.6 cells/µL)) compared to the HC group (76.7 (24.3–313.2 cells/µL), p < 0.001). Lower CD133⁺/KDR⁺ levels negatively correlated with C-reactive protein (CRP), with the number of teeth, and with all periodontal parameters (p < 0.001). Moreover, there was a proportional increase in CD133+/KDR+ levels with a progressive increase in number of teeth (p-trend < 0.001), while there was a proportional decrease in CD133+/KDR+ levels with a proportional increase in clinical attachment level (CAL, p-trend = 0.003), probing depth (PD, p-trend = 0.007), and bleeding sites (bleeding on probing (BOP), p-trend < 0.001) as an extent measure of periodontitis. This study demonstrated that patients with periodontitis presented significantly lower CD133⁺/KDR⁺ levels compared to HCs. Moreover, all patients presented an increase in the CD133⁺/KDR⁺ EPC levels with an extended level of periodontitis and tooth loss.

Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment.