Candida albicans has been detected in root carious lesions. The current study aimed to explore the action of this fungal species on the microbial ecology and the pathogenesis of root caries. Here, by analyzing C. albicans in supragingival dental plaque collected from root carious lesions and sound root surfaces of root-caries subjects as well as caries-free individuals, we observed significantly increased colonization of C. albicans in root carious lesions. Further in vitro and animal studies showed that C. albicans colonization increased the cariogenicity of oral biofilm by altering its microbial ecology, leading to a polymicrobial biofilm with enhanced acidogenicity, and consequently exacerbated tooth demineralization and carious lesion severity. More importantly, we demonstrated that the cariogenicity-promoting activity of C. albicans was dependent on PHR2. Deletion of PHR2 restored microbial equilibrium and led to a less cariogenic biofilm as demonstrated by in vitro artificial caries model or in vivo root-caries rat model. Our data indicate the critical role of C. albicans infection in the occurrence of root caries. PHR2 is the major factor that determines the ecological impact and caries-promoting activity of C. albicans in a mixed microbial consortium.

Solitary chemosensory cells (SCCs) are epithelial sentinels that utilize bitter Tas2r receptors and coupled taste transduction elements to detect pathogenic bacterial metabolites, triggering host defenses to control the infection. Here we report that SCCs are present in mouse gingival junctional epithelium, where they express several Tas2rs and the taste signaling components α-gustducin (Gnat3), TrpM5, and Plcβ2. Gnat3^−/− mice have altered commensal oral microbiota and accelerated naturally occurring alveolar bone loss. In ligature-induced periodontitis, knockout of taste signaling molecules or genetic absence of gingival SCCs (gSCCs) increases the bacterial load, reduces bacterial diversity, and renders the microbiota more pathogenic, leading to greater alveolar bone loss. Topical treatment with bitter denatonium to activate gSCCs upregulates the expression of antimicrobial peptides and ameliorates ligature-induced periodontitis in wild-type but not in Gnat3^−/− mice. We conclude that gSCCs may provide a promising target for treating periodontitis by harnessing innate immunity to regulate the oral microbiome.

Sucrose has long been regarded as the most cariogenic carbohydrate. However, why sucrose causes severer dental caries than other sugars is largely unknown. Considering that caries is a polymicrobial infection resulting from dysbiosis of oral biofilms, we hypothesized that sucrose can introduce a microbiota imbalance favoring caries to a greater degree than other sugars. To test this hypothesis, an in vitro saliva-derived multispecies biofilm model was established, and by comparing caries lesions on enamel blocks cocultured with biofilms treated with sucrose, glucose and lactose, we confirmed that this model can reproduce the in vivo finding that sucrose has the strongest cariogenic potential. In parallel, compared to a control treatment, sucrose treatment led to significant changes within the microbial structure and assembly of oral microflora, while no significant difference was detected between the lactose/glucose treatment group and the control. Specifically, sucrose supplementation disrupted the homeostasis between acid-producing and alkali-producing bacteria. Consistent with microbial dysbiosis, we observed the most significant disequilibrium between acid and alkali metabolism in sucrose-treated biofilms. Taken together, our data indicate that the cariogenicity of sugars is closely related to their ability to regulate the oral microecology. These findings advance our understanding of caries etiology from an ecological perspective.

As one of the most common oral diseases in kids, early childhood caries affects the health of children throughout the world. Clinical investigations show the copresence of Candida albicans and Streptococcus mutans in ECC lesions, and mechanistic studies reveal co-existence of C. albicans and S. mutans affects both of their cariogenicity. Clearly a comprehensive understanding of the interkingdom interaction between these two microorganisms has important implications for ECC treatment and prevention. To this end, this review summarizes advances in our understanding of the virulence of both C. albicans and S. mutans. More importantly, the synergistic and antagonistic interactions between these two microbes are discussed.

Dental diseases occurring on young permanent teeth usually lead to the premature arrest of tooth root development. Sustained tooth root elongation is necessary to achieve the goal of long-term preservation of affected teeth. To this end, stem cell-based regenerative endodontic treatment has been regarded as one of the most promising strategies for treating young permanent teeth with pulp and periapical infections. Endogenous stem cells residing in the apical papilla, named stem cells from the apical papilla (SCAPs), have been intensively investigated due to their critical roles in pulp regeneration and root redevelopment. The present review summarizes advances in the field of SCAPs studies and discusses the challenges that need to be further addressed.

Streptococcus mutans (S. mutans) is the main pathogenic bacterium causing dental caries, and the modes in which its traits, such as acid production, acid tolerance, and adhesion that contribute to the dental caries process, has been clarified. However, a growing number of animal experiments and clinical revelations signify that these traits of S. mutans are not restricted to the detriment of dental tissues. These traits can assist S. mutans in evading the immune system within body fluids; they empower S. mutans to adhere not merely to the surface of teeth but also to other tissues such as vascular endothelium; they can additionally trigger inflammatory reactions and inflict damage on various organs, thereby leading to the occurrence of systemic diseases. These traits mostly originate from some correlative findings, lacking a comprehensive evaluation of the impact of S. mutans on systemic diseases. Therefore, this review mainly centers on the dissemination route of S. mutans: “Entering the blood circulation - Occurrence of tissue adhesion - Extensive possible proinflammatory mechanisms - Concentration in individual organs” and analyses the specific effects and possible mechanisms of S. mutans in systemic diseases such as cerebral hemorrhage, inflammatory bowel disease, tumors, and infective endocarditis that have been identified hitherto.