How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: an oral microbiota perspective

Abstract

Dental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.

Fig. 1. Cariogenic biofilm formation.

EPS exopolysaccharides, Gbps Glucan-binding proteins, gbp encode Gbps, be related to adhesion, Gtfs Glucosyltransferases, gtf encode Gtfs, be related to the synthesis of EPS, eno encode Bacteria enolase, be related to glucose uptake, LDH lactate dehydrogenase, ldh encode LDH, be related to acid production, PTS phosphotransferase, the glucose uptake system, PEP phosphoenolpyruvate, atpD encode F₁F₀-ATPase, be related to acid resistance, ATP adenosine triphosphate, ADP adenosine diphosphate, AgDs agmatine deiminase system, aguD encode AgDs, be related to acid resistance. Healthy teeth develop dental caries due to the complex interactions between the host, diet, and microorganisms. The microecology of healthy teeth is based on the balance between acidogenic and alkalinogenic microbial activities, as well as the balance between demineralization and remineralization processes. When acidogenic microorganisms become predominant, frequent and high concentrations of acid locally lead to net demineralization of dental enamel, resulting in the formation of cavities. At the micro level, the initial step involves the adhesion of some primitive colonizing microorganisms to the dental enamel. The second step involves the production of EPS by the microorganisms, forming a biofilm. In the third step, acidogenic and acid-tolerant microbial communities, mainly dominated by S. mutans, establish a highly acidic microenvironment, leading to demineralization of the dental enamel. In the fourth step, the highly acidic microenvironment confers a growth advantage to S. mutans-dominated microbial populations. Taking the virulence factors of S. mutans as an example, the synthesis of EPS is primarily mediated by Gtfs. The adhesion process is mainly facilitated by Gbps. Acid production involves the participation of enolase and LDH. Acid tolerance processes primarily rely on the involvement of F₁F₀-ATPase and AguD.

Fig. 2. The mechanism of probiotics to prevent dental caries.

It is roughly divided into five parts. A Production of active metabolites: probiotics directly inhibit cariogenic pathogens by active metabolites (e.g., bacteriocin, enzyme, biosurfactants, organic acids, and hydrogen peroxide), which themselves have bacteriostatic activity. B Inhibition of cariogenic microbial biofilm: probiotics can inhibit or remove the biofilm of oral cariogenic microorganisms. C Competitive adhesion and colonization: probiotics not only occupy the colonized sites in the oral cavity but also inhibit the adhesion ability of cariogenic microorganisms. D Coaggregation with pathogens: probiotics inhibit cariogenic microorganisms colonization in the oral cavity through co-aggregation. E Regulation of the immune system: probiotics activate or modulate the host immune system, thereby enhancing the immune response to cariogenic microorganisms (enhances salivary levels of human neutrophil peptides 1–3).