Early childhood caries

Dental caries is one of the most prevalent diseases affecting people in industrialized countries. Caries of enamel surfaces (enamel caries) is particularly common in children (ECC) and young subjects up to the age of 20 years, while root surface caries is frequently observed in elder individuals with gingival recession exposing the vulnerable cementum to microbial colonization (Fig. 1) [3].

The ECC lesion invariably originates as small demineralized area on the external surface of erupted teeth, i.e., the enamel, which is the most highly calcified tissue, composed of 95% hydroxyapatite. The lesion can progress through dentin and into pulp centripetally increasing in size and depth. Demineralization of hydroxyapatite is caused by acids, particularly lactic and formic acids, which are produced from the microbial fermentation of dietary carbohydrates, resulting in the transport of the calcium and phosphate ions away into the surrounding environment. Thus, the dietary carbohydrates and infection of cariogenic bacteria on the surface of tooth enamel are essential factors in the development of ECC.

Killian Clarke 1924 Dental Caries
Figure 1. Structure of tooth and periodontal tissues. The structure of tooth and periodontal tissues are indicated in left half. The right half illustrates the host-parasite relationship in gingival crevice.

Mutans streptococci and etiology of ECC

The first description regarding the association of Streptococcus mutans with human caries was made by Clarke in 1924 [4], and numerous studies have been performed to elucidate the causative relationship between specific oral bacterial species and dental caries. In animal experiments including monkeys, gerbils, mice, rats and hamsters, most studies indicated the cario-genicity and the transmissibility of mutans streptococci, although organisms other than mutans streptococci occasionally induce variable levels of dental caries in animals [2]. In humans, many epidemiological surveys have also found a strong association between mutans streptococci and dental caries. Thus, mutans streptococci are now considered to play an important role in the development of dental caries in humans as well as animals.

Mutans streptococci are Gram-positive, facultatively anaerobic cocci, currently known to be composed of seven species (Tab. 1). Among them, S. mutans and S. sobrinus are the species recovered from human oral microflora. An individual harbors either one or both species of mutans streptococci in the mouth, especially in the supragingival plaque, and the occurrence rate of S. mutans is commonly higher than that of S. sobrinus. The most important virulent factor of mutans streptococci as cariogenic bacteria is attributed to a group of enzymes, glucosyltransferases (GTFs), which catalyze the formation of water-insoluble and -soluble extracellular polysaccharides, glucans. Water-insoluble glucans enable the microorganisms to adhere to the tooth surface. GTFs transfer a glucose moiety derived from sucrose, disaccharide of glucose and fructose, to the end of growing glucan molecule:

Table 1. Oral streptococcal phylogenetic groups and species

Mutans streptococci

Table 1. Oral streptococcal phylogenetic groups and species

Mutans streptococci

Phylogenetic group



Natural habitat

mutans group

S. mutans S. sobrinus S. cricetus S. rattus S. dewnei S. ferus S. macacae

c/e/f d/g a b h c c

human human hamster rat monkey rat monkey

anginosus group

S. anginosus S. intermedius S. constellatus

salivarius group

S. salivarius S. vestbularis S. thermophilus

mitis group

S. sanguinis S. gordonii S. parasanguinis S. oralis S. mitis S. crista

where sucrose is the sole substrate for GTFs. Because the hydrolysis of sucrose is exergonic (AGĀ°=-6.6 kcal/mol), the formation of glucan is irreversible. Glucan commonly contains a(1^ 6) glycosidic linkages and is soluble, while glucan containing a(1^ 3) glycosidic bonds in addition to the a(1^ 6) glycosidic linkages becomes insoluble. S. mutans and S. sobrinus produce three and four GTFs, respectively, whose cooperative actions are essential for the adhesive water-insoluble glucan synthesis that leads to cariogenic plaque formation on tooth surfaces. The general features and biological characteristics of GTFs have been extensively reviewed [5-9].

In addition to the production of water-insoluble glucan, the properties of cariogenic bacteria that correlate with their pathogenicity include the ability to rapidly metabolize carbohydrates to acid, and to survive and grow under acidic conditions (acidogenicity and aciduricity). Mutans streptococci, as well as some other streptococci and lactobacilli, are potently acidogenic and aciduric. With the supply of sucrose, by GTFs of mutans streptococci synthesize the adhesive water-insoluble glucan, producing lactate by homolactic fermentation, which accounts for the augmented virulence of these bacteria in hosts that frequently consume high-sucrose diets. Epidemiological observations support the sucrose-caries-mutans streptococci association; an increase in the rate of dental caries occurs with increased levels of mutans streptococci in the dental plaques and a decrease in the rates of dental caries among patients who were urged to reduce their frequency and level of sucrose consumption [10]. Thus, mutans streptococci are the primary cario-genic bacteria in ECC. It is most likely that mutans streptococci can adhere to smooth tooth surfaces through the de novo synthesis of the adhesive glucan from dietary sucrose by their GTFs, whereby they can colonize and grow exclusively at these sites and produce lactate causing the demineral-ization of enamel. The model of 'sucrose-caries-mutans streptococci association' explains the impact of sucrose (compared with glucose, fructose, starch, and sorbitol) on caries in studies of humans [11, 12].

An alternative etiology of dental caries

Despite a number of findings supporting the sucrose-caries-mutans streptococci association, an alternative hypothesis of the etiology of development/ onset of dental caries has been proposed by Marsh [13]. The hypothesis (the 'ecological plaque hypothesis') is based on the in vitro observation regarding relationship between pH and growth of plaque bacteria in a mixed culture mimicking plaque microflora. In this experiment, it was demonstrated that a decrease of pH could induce a marked growth of mutans streptococci as well as Lactobacillus casei, and that a microbial shift with the predominance of these cariogenic bacteria and with the reduction of non-mutans streptococci such as S. sanguinis and S. oralis in the mixed culture could observe under lower (but not neutral) pH conditions. The ecological plaque hypothesis does not exclude the sucrose-caries-mutans streptococci association, but acknowledges also the significant role of the local environmental conditions in plaques. It is proposed that cariogenic mutans streptococci may also be present at sound sites, but at levels too low to be clinically relevant, and that frequent metabolism of fermentable carbohydrates in plaque induces the critical pH condition, which leads to the growth of acid-tolerating cariogenic bacteria. This hypothesis may explain the data of Nyvad and Kilian [14], who indicated that the composition of non-mutans streptococcal microflora in plaque could be a factor that governs the cariogenic potential of mutans streptococci.

Reevaluation of the colonization of mutans and other oral streptococci in childhood and its relationship to ECC

According to the ecological plaque hypothesis, the development/onset of ECC could be associated not only with the colonization of cariogenic mutans streptococci but also the local environmental conditions including the colonization of non-mutans streptococci in plaque. Although the distribution of non-mutans streptococci has been monitored in some early cross-sectional studies, most of these clinical studies employed conventional identification assays with culture methods, and are still limited in scope. Mitis-salivarius agar containing crystal violet and tellurite is widely used in isolating of oral streptococci [15]. Crystal violet and tellurite inhibit the growth of most Gram-negative bacilli and most Gram-positive bacteria except streptococci. For selective culture for mutans streptococci, mitis-sali-varius agar supplemented with bacitracin, an antimicrobial agent for oral streptococci except mutans streptococci, is commonly used, although some researchers reported the inhibition in growth of some species of mutans streptococci [16, 17].

Recently, the polymerase chain reaction (PCR) has been applied for detection of bacterial species including mutans streptococci and other oral streptococci [18-22]. The PCR method offers a rapid and highly sensitive means of specific identification when compared to other identification assays, including culture and immunological methods. How the colonization of mutans and other oral streptococci in plaque of children varies with age, and the relationship between colonization of these bacteria and caries development are still not clear, since the reported studies monitored only mutans streptococci, or focused on the bacteria in saliva. Thus, species-specific PCR assays for mutans and other oral streptococcal species targeting GTF and 16S rRNA genes have been developed, which enable specific detection of 0.5-10 pg genomic DNA, corresponding at least to 100 CFU bacteria. Using the species-specific PCR assays, the colonization of S. mutans, S. sobrinus, S. gordonii, S. sanguinis, S. oralis, S. anginosus and S. salivarius in plaque samples from children was assessed in relation to caries prevalence. In the plaque samples from 320 children (0-15 years old, 20 subjects from each year of age), S. mutans (68.8%) was most frequently detected among the seven streptococci, and S. sobrinus and S. gordonii were more rare (15.0% and 17.2%, respectively). The percentages of S. mutans- and S. anginosus-positive subjects increased with age, while the percentage of S. sanguinis-positive subjects decreased. The proportional changes with age of increase of S. mutans and S. anginosus and decrease of S. sanguinis may be attribute to the gradual increase of caries scores with age. The subject-based analysis noted a significant positive correlation between S. mutans colonization and the caries score. Furthermore, there was a tendency to elevated caries scores in the group of children with mixed colonization of S. mutans and S. sobrinus, in accordance with the data of Seki et al. [23], who examined 20 variables in a univariate analysis to predict caries development in preschool children. Although the etio-logical involvement of mutans and other streptococci in plaque cannot be fully determined by itself, cross-sectional surveys have the advantage that a large number of subjects can be analyzed, and the dynamism of development of cariogenic and non-cariogenic microflora can be monitored. The cross-sectional survey using species-specific PCR assays indicated that many oral streptococcal species including mutans streptococci can colonize quite early in childhood without development of ECC, and thereafter proportional changes of microflora could occur on some tooth surfaces, where the composition of non-mutans streptococcal microflora may affect the local environmental conditions in plaque that governs the cariogenic potential of mutans streptococci.

Preventive strategies of ECC

In theory, ECC can be prevented by (1) eliminating cariogenic bacteria, especially mutans streptococci, from plaque microflora, (2) increasing resistance of tooth surfaces against acid attack, and (3) avoiding frequent high-sucrose diets.

Regarding the first category, mechanical debridements of supragingival plaque is effective. However, the infection of the tooth surfaces is the primary point of attack and the pioneer bacteria of oral streptococci including mutans streptococci are adsorbed within 2 h after cleaning. To maintain clean conditions at the tooth surface, topical chemotherapy using antimicrobial agents, glucan-hydrolyzing enzymes, and vaccination and passive immunization against mutans streptococci have been developed or investigated. Fluoride has long been known to have anti-caries effects, most of which are ascribable to (a) the interaction with the surface of enamel of erupted teeth to form fluoroapatite that strengthen the resistance of enamel to acid attack [24], and (b) the enhancement of local remineralization of the partially demineralized enamel surfaces [25]. Furthermore, it was demonstrated that fluoride has the ability to suppress the growth of mutans and other cariogenic bacteria [26, 27], and, especially under low but not neutral pH conditions, can slow the acid production at low concentrations (1 mmol/l) [13, 28].

Since dental caries is a dietary-conditioned oral infection, avoiding the frequent intake of fermentable carbohydrates, especially sucrose, in diets is important for the prevention of ECC. The historical association of dietary sucrose with caries is strong and many epidemiological studies revealed the relationship between caries prevalence and sugar consumption [11, 29]. A number of sugar substitutes (non-cariogenic sweetener) that are hardly fermented by plaque bacteria have been developed. Among them, sugar alcohols including xylitol and sorbitol are effective as non-cariogenic sugar substitutes through the inhibition of intracellular metabolisms of carbohydrates. In particular, xylitol has a unique caries-reducing effect, the so-called xylitol futile cycle. The agent is transported into mutans streptococci by the fructose-bacterial phosphotransferase system, and it enters a futile cycle of phosphorylation, dephosphorylation and eventual expulsion. The xylitol futile cycle leads to the reduction of cell growth and results in the elimination cariogenic mutans streptococci in the plaque [30].

Since early acquisition of mutans streptococci is a major risk factor for ECC [31] and future caries experience [32, 33], preventing the transmission of these organisms to naive infants' mouths is another potential strategy. Recent studies demonstrate that acquisition of mutans streptococci in infants occurs not only by vertical transmission from mothers but also by horizontal transmission from individuals in intimate proximity [34]. Moreover, primary oral infection of mutans streptococci may occur occasionally in predentate infants [35]. Thus, the reduction of the mutans streptococcal reservoir in the mother as well as sibling(s) and the infant's caretaker(s) is needed for effective prevention of ECC.

Infective endocarditis caused by oral streptococci

The most predominant pathogens of infective endocarditis are the bacterial species in the oral cavity such as mutans and other oral streptococci [36]. The tooth-tissue interface can be a typical portal for bacteria to enter the body, and nearly all physical entries of the organisms into the bloodstream. In the case of the subjects with cardiac valvular abnormalities, the organisms entering the blood stream can potentially attach and grow, and then cause the infective endocarditis. Furthermore, the glucan-synthesizing ability of these streptococci may play an important role in the etiology, since cell-bound glucan could promote the establishment of mutans and other oral streptococci on the heart valves [37, 38]. Thus, the adherence-promoting ability of glucan synthesized by mutans streptococci appears to be the initial step in the pathogenesis of infective endocarditis as well as dental caries.

5 Ways To Get Rid Of The Baby Fat

5 Ways To Get Rid Of The Baby Fat

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