The Current Strategies in Controlling Oral Diseases by Herbal and Chemical Materials

1. Introduction

Oral cavity provides an environment that leads to the colonization and growth of an extensive range of microorganisms. Bacteria are the most prevalent of them. The highest bacterial accumulation is found as a biofilm on the tooth surface (dental plaque). The loss of mucosal surface reduces the microbial load on the mucosal surfaces [1, 2]. These microbes normally exist on all oral surfaces and are necessary for the normal physiological growth of the oral cavity [3]. Static microflora contributes to the host health by preventing the establishment and colonization of exogenous microorganisms and potential pathogens and regulating the inflammatory response of the host to oral commensal bacteria [4]. The oral bacterial population with almost 1000 species is very complicated [5]. The clinical treatment of caries usually deals with the restoration of hard tissues considering the functional and aesthetic needs. However, this does not treat the illness but treats its outcomes. In clinical settings, a common method for the management of dental caries is the elimination of contaminated tissues to prevent the further progress of the disease. The areas surrounding the restoration gradually undergo caries, so a small restoration must be substituted by a greater restoration and dental tissues are increasingly eliminated. Repetition of this cycle leads to extensive loss of dental tissue, pulpal involvement, and finally tooth loss [6]. Admittedly, an inadequate understanding of dental caries as a biological process leads dentist to such a problem. Considering the developments in genetics, particularly molecular biology, findings make it possible for us to replace the old paradigms with new ways of caries prevention and treatment. Dental decay is caused by an ecological imbalance in mouth microflora. These imbalances can be influenced by environmental and biological reasons. Dental caries can be controlled by managing the above mentioned changes [7, 8]. In this review, we aimed to study the recent research to identify the characteristics of dental biofilm and its role in dental caries and also explore the employed methods to prevent the related infections.

2. Caries and Its Stages

Dental caries is a chronic and preventable disease caused by dental biofilm activity. This disease is multifactorial and is initially caused by an imbalance of mouth microflora as a result of existence of carbohydrates on the tooth. Caries is characterized by local demineralization of the teeth and loss of dental structure. Some biofilm bacteria metabolize the existing carbohydrates and produce acids. These acids can reduce the pH and reach lower than the critical limit (5.5 for enamel and 6.2 for dentine) if they remain in the biofilm for a long time. This acidic environment affects the biofilm composition and tooth surface. Therefore, acidogenic and acidophilic bacteria increase, which results in a more acidic environment. Calcium and phosphate are removed from the tooth surface, as a result of which demineralization occurs due to the loss of minerals. If pH returns to its normal level, calcium and phosphate can return to the tooth structure and cause remineralization [9]. Dental caries is created on the surface and subsurface areas of the tooth following a dynamic trend of demineralization and remineralization. These events occur several times over time and are influenced by several factors like the type and number of biofilm microorganisms, diet, oral hygiene, genetics, tooth anatomy, fluoride consumption, and salivary content and composition. These factors are specific to each individual and vary from tooth to tooth and from place to place [9]. As demineralization continues, primary caries occurs, a lesion with no cavities called white spot lesion (WSL) on enamel. Most primary caries can be terminated or remineralized; i.e., they are reversible. Dental caries becomes cavitated as it progresses. Cavitated lesions often need restorative intervention and are irreversible. Moderate lesions are lesions that have not extended the internal one-third of the dentin, and advanced or deep lesions are those that have extended the internal one-third of the dentin [9].

3. Dental Plaque

Dental plaque is a soft and sticky layer accumulated on the tooth surface. Dental plaque, also called biofilm, mostly consists of bacteria and their products, extracellular matrix, and water. Biofilm is not sticky food debris or accidental accumulation of opportunistic microorganisms; it is the accumulation of a series of organized events. The formation of dental plaque involves the formation of the pellicle, initial attachment, and plaque maturity [10]. Plaque forms as follows: a clean tooth surface is immediately exposed to the salivary byproducts, gingival crevice fluid (GCF), and some compounds resulting from bacteria. These products are absorbed by the surface with a negatively charged hydroxyapatite, creating a layer called acquired pellicle. The dental pellicle is covered with positively charged molecules, which contain more than 180 proteins, peptides, and glycoproteins such as proline-rich proteins, histidine-rich proteins, phosphoproteins (e.g., statherin), creatine, mucin, and other molecules that act as the binding sites for bacteria [10]. Some bacterial products like glycosyltransferases and glucans are also found in the pellicles. Interestingly, the main compound of a pellicle is stable in different areas of the oral cavity and among individuals. The bacteria attached to the tooth surface are not directly connected to the enamel; they are bound to the enamel through pellicle [10]. Primary bonding is initiated a few minutes after brushing the colonization. A cell wall with negatively charged bacteria facilitates its connection to the positively charged receptors of the pellicle. The early stages of transfer and interference with the surface are similar and nonspecific for all bacteria. Specific involvement of the binding molecules of the bacterial cell wall and pellicle receptors determines whether the bacteria remain in contact with the surface or not. Only a small part of oral bacteria can bind to the pellicle receptors, which constitutes the most common biofilm bacteria over a short time after tooth cleaning. During the early hours, streptococci form over 60–80% of biofilm bacteria. These bacteria along with Haemophilus, Neisseria, Actinomyces, and Veillonella species are known as primary colonizers. They initially create a wide range of nonspecific and reversible Van der Waals connections with pellicle (more than 50 nm). Then, they make stronger and irreversible short-range connections (10–20 nm) with pellicle receptors by their specific surface molecules [10].

Streptococci create different adhesion mechanisms. They have different adhesion mechanisms such as products of glycosyltransferases, glucan-binding proteins, and pili, while other bacteria such as actinomycetes bind to the surface using their fimbriae [11]. These bacteria provide new adhesion sites for other bacteria and change the environment with their metabolic activity, thereby affecting the biofilm viability (e.g., reducing the ambient oxygen) [11]. Plaque matures as follows: the primary colonizing bacteria bound to the tooth surface provide new receptors for the bacteria to help induce coadhesion via binding. The bacteria of different species or even strains of a species can specifically bind to specific bacteria. Fusobacterium coaggregates with all oral bacteria, while Veillonella, Capnocytophaga, and Prevotella coaggregate with streptococci or actinomycetes. Most of this adhesion between various bacteria is performed through lectin-like receptors (proteins that identify the carbohydrates). Thus, they can be inhibited by lactose or other galactosidase or amino acids like L-arginine [10, 12]. Secondary colonizers like P.Int, FN, Prevotella loescheii, Capnocytophaga, and PG cannot bind to the clean tooth surface but can bind to bacteria in the dental plaque. Some specific structures in dental biofilm such as corn cob and test-tube brush are created due to the adhesion of cocci to filamentous bacteria. In this stage of plaque maturity, the bacteria secret extracellular polysaccharide, which constitutes the biofilm scaffold [10, 13]. If the dental plaque remains for about 7 days, it provides a favorable environment for the colonization of some aerobic Gram-negative bacteria, which are called secondary colonizers, including PG, Aggregatibacter actinomycetemcomitans, and Treponema denticola [10, 13].

4. Dental Biofilm

A healthy dental biofilm is mostly composed of commensal nonpathogenic microbes. These microbes are not completely independent and are regularly linked with each other and host tissues like gingiva even in a healthy state. The host provides the surfaces for colonization, and beneficial bacteria prevent the colonization of pathogenic bacteria [4, 14]. The advantages of this connection are manifested in conditions such as antibiotic sore mouth when inhibition of normal flora leads to the growth of opportunistic pathogens [4]. Studies have shown that commensal bacterial species such as S. salivarius, S. sanguis, and Atopobium parvulum can induce biofilm health-related conditions. Nevertheless, further research is needed to explore this issue. It has been shown that S. salivarius inhibits the quorum sensing process and mutans biofilm formation, which results in its anticaries properties [15–17]. The commensal bacteria in biofilm are involved in the immune system development. They do this by presenting diverse antigens to the host immune system. The commensal bacteria create a cascade of signals that induce the host resistance, while pathogenic bacteria induce severe inflammation in the host. Hence, proinflammatory cytokines are produced in a low number in oral epithelial cells, which induces the expression of E-selection in vascular endothelial tissues and produce IL8 [10]. The commensal bacteria induce the innate immune response of the host, which strategically juxtaposes the neutrophils with subgingival bacteria and junctional epithelium. The main bacteria with the highest variation in the oral cavity include S, Staphylococcus, Peptostreptococcus, P, Haemophilus, Veillonella, Leptotrichia, Treponema, Propionibacterium, Actinomyces, Fusobacterium, Corynebacterium, Eikenella, Gemella, Granulicatella, Rothia, Porphyromonas, Capnocytophaga, L, Neisseria, and Eubacteria [18–20]. Oral health depends on the conservation of its normal microflora. A disease occurs once the species are imbalanced and pathogens become dominant. Oral health and disease are dynamic processes in which the ecology of communities is a determinant factor, not an organism. Understanding the meaning of and identifying the molecular changes among the disease and health conditions provide the clinicians with the ability to diagnose and reverse the disease in early stages [21].

5. Bacterial Groups in the Caries Process

The newest molecular biology methods of microorganisms related to caries are B. dentium, B. adolescentis, SM, Scardovia wiggsiae, B. longum, Selenomonas spp., P. spp., and L. spp. [16]. Studies have indicated that early streptococci on the newly cleaned tooth surface mostly include S. sanguinis, S. oralis, and S. mitis strains, and the content of their mutans is only 2% or less. It has also been shown that most primary colonizers belong to the S. mitis group. The amount of microflora actinomycetes increases over time so that the smooth surfaces of most bacteria in the mature plaque include actinomycetes and nonmutans streptococci. Mutans are found in small numbers [22] and are more abundant in white spot lesions (WSLs) than in healthy regions. However, nonmutans streptococci still constitute most WSL bacteria. It has been shown that the initial members of microflora can singly dissolve enamel in the absence of mutans and lactobacilli [22]. In cavitated dentinal lesions, including rampant caries, mutans constitute about 30% of microflora, which indicates that mutans are linked with progressive carious lesions. Nevertheless, some studies have shown that the dentinal caries of mutans is less frequent in deep lesions, and lactobacilli, Prevotella, and bifidobacteria are more prominent. These results indicate that microflora on the tooth surfaces change as caries progresses [22]. S. mutans is Gram-positive cocci. The oral S spp. are normal flora but are also opportunistic and can cause dental caries [23]. They include SM, S. sobrinus, S. rattus, S. cricetus, S. ferus, S. downei, and S. macacae. Virulence has numerous factors that induce its demineralization [23] (Table 1).

6. Extracellular Polymeric Substance [24]

The extracellular polymeric substance [24] of the biofilm plays a pivotal role in maintaining the bacterial integrity and adhesion. New studies on the biology of EPS have reported several roles for the scaffold resulting from EPS, which are vital for the biofilm [25, 26]. Some of these roles include surface adhesion, spatial and chemical heterogeneity in biofilm, competitive or collaborative interactions, and improved resistance to antimicrobials [25]. The construction of EPS matrix relates to the existing substrates, production and secretion of e-materials, and shear forces. The key part of EPS content in oral biofilms which is related to caries is polysaccharides, especially the glucans derived from SM [27]. In addition to these, polysaccharides result from other bacteria (e.g., actinomycetes, Streptococcus salivarius, and Streptococcus gordonii), and combination compounds of starch glucan exist in this matrix. Further, this matrix contains eDNA [28] (proteins derived from bacteria with properties similar to amyloid), host GP which are able to participate in the scaffold with G such as glucan-eDNA compounds [29]. The function and structure of this class of extracellular polymers are still not known completely and require further studies. Glucans are composed of glucose components, which are connected byα 1–4 and α 1–6 glycosidic bonds and are created by the coordinated activity of streptococcal exoenzymes called glucosyltransferase [3, 27, 30]. Interestingly, these extracellular enzymes can bind to the tooth structure in the active state and produce glucans locally, thereby providing new binding sites for the bacteria. In addition to these, glucosyltransferase enzymes bind to other oral microorganisms (e.g., commensal S, actinomycetes, L, and even Candida albicans) and make them G producers [3, 27, 30].

The G produced on the tooth surface increase the surface bacterial aggregation. They also cause new interspecies interaction and increase cell-cell adhesion [3]. These extracellular polymers aggregate on different areas of tooth surface on the cell membrane, each having a complementary role in the EPS matrix formation and biofilm development. Some of these roles are surface adhesion, cell-cell adhesion, and cell cluster development found in the biofilm systems [31]. The biofilm matrix is developed three-dimensionally with biofilm maturation and production of extracellular polymers, covering cell clusters, building bridges between them, and creating a firmly divided structure. This heterogeneous structure resulting from EPS explains the presence of microbial clusters in various sizes and composition in the human oral biofilm [32–34]. The EPS sediment on the surface and its development affect the mechanical properties of biofilm like the binding strength of biofilm to the surface and its integrity [35]. A well-formed biofilm is hardly removed from the tooth surface and has reinforced viscoelastic properties that help it to remain on the surface during the shear stresses exerted by liquids [35]. The structure of the EPS matrix can be locally altered by dextranases, DNAs, and protolithic enzymes to create new binding sites for the following bacteria that have not been able to join the biofilm. The stiffness of the biofilm matrix is increased over time. The physicochemical properties of biofilm protect the buried bacteria by inhibiting the access of drugs and increasing their AM resistance. For instance, EPS can bind to cationic AM like CHX and AM peptides and prevent their permeation into the depth of biofilm, thus preventing their toxic effect [3, 34].

7. Fighting Dental Caries

The caries-preventive strategies can be classified into three groups depending on the role and responsibility of the individuals doing them (Figure 1): (1) community-based strategies, (2) dental professionals-based strategies, and (3) individual-based strategies. The dental professionals-based strategies include professional tooth cleaning and use of varnish, fluoride gel and foam, fissure sealant, and antimicrobial agents. The individual-based (self-care) strategies consist of using fluoride toothpaste, fluoride supplements, fluoride mouthwashes, fluoride gels for personal use, chlorhexidine gels and mouthwashes for personal use, slow-release fluoride devices, oral health, diet control, and noncariogenic sweeteners like xylitol [36]. Recent studies (2015–2020) are mentioned in Table 2.

8. Communal Activity-Based Methods

9. Dental Professionals-Based Methods

10. Self-Care Methods for Caries Prevention

11. Oral Hygiene

The tooth surfaces free of biofilm are not decayed. Patients should regularly eliminate biofilm by brushing with fluoride-containing toothpaste and dental floss [9, 159]. The oral biofilm composition changes over time following oral hygiene by regular brushing twice a day, and oral microbiome is maintained in the healthy state [160]. The brushing does not remove oral bacteria totally but rather eliminates them from the tooth surface. A massive amount of them is removed from the mouth after swallowing and/or rinsing after brushing and flossing; however, an enough number of them stay for proliferation. Cleaning and exposing to oxygen may kill anaerobic organisms; however, no species is eliminated. Accurate mechanical tooth cleaning disrupts the dental biofilm and cleans tooth surface. While all bacteria that constitute established biofilm still do not exist, most of them are not able to bind to the clean tooth surface [9]. Brushing and flossing are advantageous in that they do not destroy the oral normal flora. Frequent mechanical removal of biofilm does not cause the risk of opportunist infection but rather changes the biofilm’s composition. Patients with good oral hygiene have a high percentage of S. mitis or S. sanguis in their teeth biofilm and have a smaller amount of cariogenic bacteria than the more developed biofilm having a high amount of S. mutans [9]. Nevertheless, it should be emphasized that the former concepts of plaque removal or accurate control of another plaque are not considered for the management of caries. Proper oral hygiene is certainly important for biofilm control, but systemic review studies have shown that mechanical removal of biofilm alone, in the absence of fluoride, is not enough to manage caries [158].

12. Conclusion

One of the basic aspects of general health is oral health. Oral diseases cause many problems for individuals and society. They are very common all over the world. While there are effective methods for and adequate information about the prevention of oral diseases, they are still one of the most prevalent health problems. The best strategy to fight caries is the use of a combination of community-based strategies, oral health professionals-based strategies, and self-care strategies. The most important strategies to fight against caries are paying attention to the oral health in macroeconomic policies of countries to create a healthy society, changing the attitude of dental professionals from a treatment-centered approach to a preventive approach, and empowering the individuals by enhancing their knowledge, attitude, and performance in line with maintaining and promoting their oral health.

13. Future Directions

Despite many attempts made to control caries, these efforts have not been effective in controlling caries. Further studies are suggested to identify the confounding factors of biofilm such as natural antimicrobial materials that, unlike antibiotics, do not cause bacterial resistance and are cheap and available to everyone. Moreover, more studies are required on probiotics and production of S. mutans strains that are not able to produce lactic acid by recombinant DNA technology or other bacteria that competitively eliminate the microbial cariogenic agents of the oral cavity and manufacture of slow-release devices for antimicrobials such as fluoride in the oral cavity and silver nanoparticle pins that prevent caries by releasing antimicrobial agents. Furthermore, we suggest conducting future studies on the production of caries vaccine to induce biologic defense against caries in the oral cavity and creation of protective layers on the tooth that act beyond the current sealants in terms of gear, duration, and caries prevention.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

The authors declare that this work was done by the authors named in this article. Mohammad Nima Motallaei, Mohsen Yazdanian, Hamid Tebyanian, Elahe Tahmasebi, Reza Ranjbar, and Alireza Yazdanian were involved in study design and data collection. Mohsen Yazdanian, Hamid Tebyanian, Elahe Tahmasebi, and Alexander Seifalian critically reviewed the data and wrote the review article.