Probiotics: Dawn of a New Era in Dental Caries Management.

Dental caries is considered to be the most common pathology of the oral cavity. The pathogenesis of dental carries is believed to be because of imbalance in the microbiological niche creating an ecological pressure. Probiotics are living microorganisms which when dispensed in appropriate amounts can benefit the health of the host. They have posed as a promising replacement to antibiotics that can aid in solving dental issues like dental caries. There are numerous Randomized control trials to validate this fact. There are also various modes through which a probiotic can be delivered against dental caries. Numerous new avenues like effector strains and synbiotics are also explored nowadays. The present review is about the significance of probiotics in the management of dental caries. Copyright:

INTRODUCTION

Lately, the oral cavity has been proposed as a pertinent target for probiotic applications. Present day researches have proved that an equilibrium between favorable and disease-causing bacteria determines the oral health of the pro-individual. The past decade has seen the exploration of products bearing probiotic as a likely substitute for oral health therapy.[1] Biofilm forming on the oral hard tissues and soft tissues is contemplated to be the principal causal agent in periodontal problems and caries which are considered as the most common pathological conditions of the oral cavity.[2]

It is well versed now that diseases like caries and periodontal diseases emerge due to environmental disturbances to the oral habitat. This has been summed up in the 'ecological plaque hypothesis.[2] Ecological plaque hypothesis proposes that minimal pathogens causing caries may be present or may be transmitted in the oral biofilm determines oral health. Any loss of equilibrium in this biofilm-producing changes in local environment leads to an increase in pathogens causing dental caries. A carbohydrate-rich diet, reduced salivary flow, and low salivary pH are some of the changes cumulatively termed as “ecological pressures”.[2]

Pathogens that compete with the indigenous microflora in an ecological pressure situation approach numerical dominance levels required for occurrence of the disease. This concept strengthens the recent definition of dental caries to be a complex disease. The endogenous rather than exogenous pathogenic species are primarily associated with its development. The number of endogenous organisms remarkably rises in an intraoral environment favorable to them. Hence, prevention of caries can be achieved by two methods: (A) by directly targeting the potential pathogen and (b) indirectly by hindering “the ecological pressure” of the responsible pathogen selection.[3]

Probiotics have posed as a promising substitute to antibiotics that can be effective against oral diseases such as periodontal disease, halitosis, and dental caries which are related to an imbalance in the microbiota. For the probiotics to act, several methods have been proposed, namely competitive exclusion, direct and indirect interaction.[4] This review attempts to explore the importance of probiotics in preventing or controlling dental caries.

Dental caries

Dental caries is considered to be the most common chronic multifactorial disease affecting the mineralized structure of the teeth in oral cavity. The susceptibility to this disease persists throughout.[2] The factors involved in the formation of dental caries are nutrition, oral hygiene maintenance, fluoride, and the cariogenic bacteria colonization, which attributes to the food intake, cultural practices, socioeconomic status, and lifestyle.[5] The host-related risk factors are salivary flow and its buffering capacity, teeth position in relation to their neighbors, surface enamel characteristics, and occlusal fissures topography on posterior teeth.[678] Bacteria in their communities within the dental plaque accumulated on the tooth surface cause tooth structure demineralization and destruction leading to dental caries.[1] The primary bacteria involved in the formation of caries are Streptococcus mutans and Lactobacilli spp.[9] Inside the biofilm, carbohydrates ferment into organic acids as metabolic by-products lowering the pH levels which leads to tooth structure demineralization.[10]

S. mutans is a pivotal pathogen in the formation of dental caries due to its ability to produce biofilms. Conversion of sucrose to the extracellular polysaccharides like glucans is crutial for biofilm formation.[11] This metabolic step relies on the various surface proteins which take part in the production of the extracellular glucan matrix are glucosyltransferases (GtfB, GtfC, and GtfD). Whereas growth of the biofilm is contributed by surface proteins like glucan-binding proteins by the bacterial interaction with extracellular glucan.[121314]

Aas et al.[15] have proved that species of Lactobacillus, Atopobium low-pH nonpremutans streptococci, Propionibacterium, Actinomyces, Bifidobacterium, and Veillonella and not only S. mutans and Lactobacilli spp can be attributed to the pathogenesis of dental caries.

Probiotics

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”[16] Probiotics promote health by secretion of antimicrobial compounds, biosurfactant production which inhibits epithelial surface adhesion, degradation of toxin, lowering blood cholesterol, host's immune system, competing for nutrients and adhesion sites, and vitamin synthesis stimulation.[4]

The oral health of an individual is determined by the balance between the beneficial and pathogenic bacteria. This makes the oral cavity a valid target for the application of probiotics.[2] The bacterial biofilm produced on the hard and soft tissues is implicated for various pathological conditions such as dental caries and periodontitis.[17] It has been observed that dental caries is not caused by a specific bacterium but by a group of bacteria sharing common physiological characteristics. It is the imbalance in the oral environment and facilitation of the pathogenic group of bacteria which leads to various infectious pathologies.[17] This is the target area where probiotics come into play. Probiotics act in the oral cavity either by direct interaction, indirect interaction, or competitive exclusion. Under direct interaction, the probiotics inhibit the addition of pathogens, become an integral part of the biofilm, and produce cytoprotective proteins on the host cell surface. The probiotics indirectly interact with the pathogenic bacteria by enhancing host immunity, regulating mucosal permeability, and affecting nonimmunological defense mechanism of the host. The probiotics also compete with the pathogens by producing inhibitory molecules against them and competing for the bonding sites.[4]

Probiotics and dental caries

To reap the beneficial effects of probiotics in keeping dental caries at bay, it must attach to tooth surfaces and hence amalgamate into the dental plaque. It should inhibit the proliferation of cariogenic bacteria by competing and antagonize the cariogenic bacteria. Moreover, the probiotic should lower acid production by metabolizing dietary carbohydrates.[2]

Many investigators studied the effect of probiotic species like Lactobacillus rhamnosus GG (LGG), Lactiplantibacillus plantarum DSM 9843, Limosilactobacillus reuteri ATCCPTA 5289 and L. reuteri ATCC 55730 on various caries forming pathogenic bacteria. L. reuteri ATCC PTA 5289 and LGG demonstrated the highest inhibitory activities whereas others showed some degree of inhibition of S. mutans proliferation and plaque formation.[181920]

Coaggregation abilities of Lactobacilli species are also attributed towards the prevention of colonization of bacteria responsible for caries and dental plaque formation.[21] S. mutans adhesion incredibly decreased when probiotics like Lacticaseibacillus casei, L. rhamnosus GG, Bifidobacterium lactis Bb12 and L. reuteri were incorporated in an in vitro system before S. mutans. These probiotics altered the protein composition of the salivary pellicle creating an artificial biofilm on hydroxyapatite that specifically prevents the adherence of S. mutans.[22] Similarly, probiotic strains such as CMS1 and CMS3, belonging to Weissella cibaria, which is a subtype of Lactobacillus also showed inhibitory effects on plaque formation.[23]

Coaggregation could be one of the manners in which probiotic averts and controls dental caries. Twetman et al.[24] and collaborators probed the coaggregation between probiotic bacteria and caries-associated strains. Lactobacillus acidophilus, L. plantarum, L. rhamnosus GG, L. rhamnosus LB21, Lacticaseibacillus paracasei subsp. F19 and L. reuteri PTA5289 were the strains chosen from the commercial dairy products. Although all of them coaggregated with oral pathogens and compared to all strains S. mutans showed a higher capability than the other pathogens to coaggregate. L. acidophilus coaggregated better than other probiotic organisms. Studies on probiotic strains aim to recognize and distinguish species which can compete or antagonize Streptococci and other pathogenic bacteria with cariogenic potential.[24] Hasslöf et al. Their study suggested that selected probiotic strains have the potential to curtail dental caries by impeding the growth of S. mutans, but the extent of inhibition remains strain specific for the probiotic and for the pathogenic strain.[25] Salivary buffering capacity has also been observed to increase when healthy volunteers were given a probiotic tablet containing L. salivarius. LGG also believed to improve the salivary buffering Capacity.[26]

Various authors such as Gizani et al. in the year 2016, Ghasemi et al. in the year 2017, Koopaie et al. in the year 2019, Zare Javid et al. in the year 2020 and Ferrer et al. in the year 2020, performed randomized control trials to identify the role of various probiotics against dental caries. All of them were successful to identify caries reducing abilities of the candidate probiotics.[2728293031]

There are many probiotic strains identified as potential candidates to be used for oral health. Table 1 summarizes the various candidates suitable to be used for the purpose.

Table 1

Candidates designated as suitable oral probiotics

Genus	Species
Lactobacillus	Rhamnosus
	Reuteri
	Casei
	Paracasei
	Achidophilus
	Salivarius
	Brevis
	Bifidum
	Bulgaricus
	Sporogens
	Thermophilus
Bifidobacterium	Animalis lactis
	Bifidum
	Longum
Streptococci	Mutans
	Rattus
	Oralis
	Uberis
	Dentisani
	Salivarius
Bacillus	Coagulans

Delivery of probiotics

Dairy products appear to be the most common vehicle for probiotic delivery. The colloidal nature of milk appears to be protective for animal enamel, due to the presence of various organic compounds and inorganic compounds which compensate the cariogenic challenges. Calcium lactate, its constituent off dairy product also have anti-cariogenic properties.[32] various dairy products which are ideal for probiotic delivery are whole milk, cheese, yogurt, add, and other allied products.[32]

It is a challenge to administer probiotics to those who are lactose intolerant or are allergic to dairy products. For them, various other means are identified. Capsule or liquid, store tablets, drops, lozenges, ice cream, and sweetened cakes are few other vehicles through which probiotics can be delivered.[3233343536373839]

Concept of effector strain

Effector strain is a nonpathogenic microorganism with the potential to colonize infection susceptible host tissues persistently pants hands hence preventing the invasion of pathogens into the host tissue. This is commonly been described as replacement therapy which aids prevention or cure of the disease. This can also lead to herd protection by the transmission of effector strain from one individual to another.[32] Certain S. mutans species with low acidogenic potential due to lactate dehydrogenase (LDH) deficiency and with the ability to produce certain bacteriocins could be used as effector strains.[404142] LDH converts pyruvate to lactic acid during the glucose metabolism by cariogenic bacteria.[43] Whereas Bacteriocin has antimicrobial properties towards the close relatives of the effector strains.[44] Present day considers the effector strains therapy to be an integral part in caries prevention and treatment. However, a thorough investigation into the capacities of effector strains and its safety will guarantee its effectiveness in the clinical scenario.[32]

Concept of prebiotics and synbiotics

The term “prebiotics,” on the contrary, is used to describe “a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the resident microflora, that confers benefits upon host wellbeing and health.” The term “symbiotic” is applied to products containing probiotics and prebiotics.[32] Prebiotics are combined with probiotics to produce a symbiotic to enhance the probiotics's ability to outgrow pathogens. Various prebiotics which are evaluated as a suitable addendum to form Synbiotics combinations are glucomannan hydrolysates or 3% galactooligosaccharides and 1% fructooligosaccharides, Xylose, xylitol, arabinose, urea, arginine.[4546474849] Undoubtedly, the concept of synbiotics in caries management has high promise. However, presently, it is in its very early stage of development. Further clinical trials to investigate their in vivo effect on the oral microenvironment, especially on dental plaque and its pH, are necessary to validate the idea.

CONCLUSION

Probiotics are established therapeutic and supplemental adjuncts for various Generalized and systemic conditions. Their role in dental caries prevention and treatment is an avenue which is explored properly in the last decade. The evidence of which is reflected in many randomized control trials. Effector strains and synbiotics are pioneer areas which may prove to be promising in caries prevention and treatment. The future requires multi-centric trials to validate the various combinations so that patients can reap the benefits of probiotics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.