Background: The objective of this study was to evaluate and present evidence from animal and human clinical studies on associations between dental caries and systemic diseases, and to suggest potential mechanisms that might explain such associations. Methods: An electronic search was conducted of PubMed, Embase and Cochrane Central Register of Controlled Trials for articles published from 2010 to 2020 in the English language. From the initial search, 404 full-text studies were assessed for eligibility. After excluding studies for technical and study limitations, a total of 67 studies were included in the summary tables and additional studies were included in the review to support evidence. Results: Few systemic disease and conditions were found to be clinically meaningfully associated with caries experience. Best evidence from human and animal studies described association between metabolic diseases and dental caries. Several interesting animal studies were noted that could generate clinical hypotheses and further investigations in rodent models for cardiovascular injury and hyperglycemia. Inadequate data was found to suggest any modifications to current clinical practice or prevention guidelines. Conclusions: Limited clinical evidence was found connecting several systemic diseases and dental caries. Inadequate data was found to suggest any modifications to current clinical practice or prevention guidelines. Clinical significance: Understanding of associations between dental caries and systemic diseases play a crucial role in the treatment planning and education of the dental patient.

Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome–derived commensals produce lantibiotics to impair pathogens’ colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis—these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.

Background and Objective: The oral microbiome plays an important role in oral health and disease, including periodontitis, which affects about 40% of the adult population in the United States. Bacterial pathogens have been well studied and documented in their relationship with periodontitis; however, the role of fungi in periodontitis is still unclear. The purpose of this study is to determine the relationship of specific fungal species with periodontal pathogenic bacteria in healthy, mild periodontitis, and severe periodontitis patients. Methods: In this study, human participants were recruited, and saliva samples were collected. Twelve participants representing periodontal health (n = 2), mild periodontitis (n = 3), and severe periodontitis (n = 7) were included. Salivary samples were sequenced for analysis of their mycobiome (ITS sequencing) and microbiome (16s RNA sequencing). Results: A total of 375 species of bacteria and 39 species of fungi were identified among all samples. Clustering was observed for bacteria in healthy and mild periodontitis, but more variability was observed in the severe periodontal disease group. Variability was observed for fungi among all samples and groups. Red complex bacteria were negatively correlated with Candida species for the disease groups, although the correlation was not statistically significant. A significant correlation was observed between red-complex bacteria in the severe periodontal disease group. Additionally, a significant correlation was observed among Candida species in all groups. Conclusions: This pilot study simultaneously processed saliva samples for microbiome and mycobiome sequencing and found a trend towards negative correlation between Candida species and red complex bacteria.

The interaction between human salivary alpha-amylase (HSAmy) and amylase-binding oral streptococci (ABS) helps determine the bacteria that colonize the oral cavity by establishing dental biofilms. Streptococci are important pioneer species of the oral cavity and influence oral health as well as common diseases such as dental caries. Various oral streptococcal species express distinct amylase-binding proteins, among which amylase-binding protein A (AbpA), encoded by the abpA gene in Streptococcus gordonii and several other species, which is the most extensively studied. Amylase binding facilitates microbial adhesion to host surfaces and biofilm formation and enables bacteria to harness the host’s amylase enzymatic activity at their cell surface, enhancing their capacity to metabolize dietary starch for nutritional gain. Additionally, amylase binding may also influence bacterial cell division and stress tolerance by engaging novel bacterial signaling pathways. From an evolutionary perspective, both Neanderthals and modern humans exhibit functional adaptations in nutrient metabolism, including selection for salivary amylase-binding oral streptococci, highlighting the importance of microbial co-adaptation in response to host diet. Further research is warranted to elucidate the broader roles of amylase binding to bacteria in host-bacterial signaling, bacterial cell division and fitness and the evolutionary trajectory of the oral microbiome.