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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 1  |  Issue : 1  |  Page : 1-5

Oral synbiosis—Current evidence and future potential


Department of Pediatric & Preventive Dentistry, Dasmesh Institute of Research and Dental Sciences, Faridkot, Punjab, India

Date of Submission11-Mar-2021
Date of Acceptance11-Apr-2022
Date of Web Publication30-Aug-2022

Correspondence Address:
Nitika Bajaj
Department of Pediatric & Preventive Dentistry, Dasmesh Institute of Research and Dental Sciences, Faridkot, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnam.jnam_6_22

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  Abstract 

The human oral cavity is colonized by a complex ecosystem of microorganisms. There are various beneficial and harmful bacteria present in the oral cavity. Beneficial bacteria have numerous and important functions, e.g., they produce various nutrients for their host, prevent infections, and modulate a normal immunological response. In order to achieve, restore, and maintain favorable balance in the ecosystem, the modification of the oral microbiota is necessary, for improved health outcomes. So, the introduction of probiotics, prebiotics, or synbiotics in a human diet could be beneficial. Probiotics are dietary supplements containing beneficial bacteria and yeast, whereas prebiotics are nondigestible dietary supplements that further stimulate the number and activities of probiotics to improve oral health. So, the combination of these two, probiotic and prebiotic, are regarded as “synbiotic.” Synbiotics are emerging as a captivating and desirable field in dentistry, which when consumed provides noninvasive treatment and thus improves the quality of life. This review article highlights the role of synbiotics in oral health and disease, as synbiotics can be considered a potential therapeutic and preventive strategy against various oral diseases.

Keywords: Bacteria, Prebiotics, Probiotics, Synbiotics


How to cite this article:
Setia R, Bajaj N, Bhola M, Brar GS. Oral synbiosis—Current evidence and future potential. J Niger Acad Med 2022;1:1-5

How to cite this URL:
Setia R, Bajaj N, Bhola M, Brar GS. Oral synbiosis—Current evidence and future potential. J Niger Acad Med [serial online] 2022 [cited 2022 Nov 27];1:1-5. Available from: http://www.jnam.com/text.asp?2022/1/1/1/354771




  Introduction Top


The role of diet and nutrition in health and wellbeing is universally accepted. With the evolution of the science of diet and nutrition, research is now directed toward improving the understanding of the particular physiologic effects of the diet beyond its nutritional effect. Nowadays, probiotics are one of the recent research subjects of nutritional science and food. The benefits of probiotics have been recognized and explored for over a century.[1] Probiotics can be bacteria, mold, or yeast. However, most probiotics are bacteria. Despite our rapidly increasing knowledge of pathogen–host interaction, the role of these beneficial bacteria in preventing the emergence of pathogenic species and oral health remains obscure. The human gastrointestinal tract constitutes an extremely complex ecosystem of the bacterial population. Most of these organisms are beneficial (e.g., Bifidobacterium and Lactobacillus), but some are harmful (e.g. Salmonella species, Helicobacter pylori, Clostridium perfringens). Some dietary substances, so-called prebiotics, can favor the growth of these beneficial bacteria over that of harmful ones. Prebiotics are nondigestible dietary supplements and are designed to improve health by stimulating growth and/or activities of probiotics such as Bifidobacteria and Lactobacilli. Adding to the benefit of probiotics in the treatment of oral diseases, prebiotics have also been found to be useful.[2]

Resulting mixture of prebiotics and probiotics is known as synbiotics. Gibson and Roberfroid in 1995 introduced this concept of “synbiotics.” It refers to nutritional supplements combining probiotics and prebiotics that are thought to act together, i.e., in synergism.[3] As the term “synbiotic” implies synergy, it should be used for those products where a prebiotic component favors a probiotic microorganism selectively.[4] Synbiotics is defined as “a mixture comprising live microorganisms and substrate selectively utilized by host microorganisms that confers a health benefit on the host.”[5]

By harnessing the benefits of these prebiotics and probiotics into synergy, the number of good bacteria increased by many folds for the betterment of our health. It works by improving the viability of probiotics and by delivering specific health benefits.[3] These are used not only for the improved survival of beneficial microorganisms added to food or feed, but also for the stimulation of the proliferation of specific native bacterial strains present in the gastrointestinal tract.[4] Synbiotics have shown numerous benefits to health including resistance to infection, antibacterial activity, antioxidant activity, and enhancing the immunity [Figure 1].[6] The combination of both components in a single product should ensure a superior effect, compared with the activity of the probiotic or prebiotic alone.
Figure 1: Mechanisms of action of synbiotics and their effects (Markowiak and Slizewska, 2017)

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  Relationship Between Prebiotics and Probiotics Top


Prebiotics when combined with probiotics have many advantages. Basically, prebiotics stimulate the growth of probiotics, which is dose- and strain-dependent. Prebiotics serve as a selective growth substrate for the probiotics strain during fermentation and during the period of storage. When combined together, they implant live microbial dietary supplements and create an amiable environment for their survival. Thereby, it improves healthy microbial balance. For the survival of a true probiotic, the availability of prebiotic food is essential. Without the necessary food source for the probiotic, it will not be able to tolerate high oxygen and low pH and temperature. As prebiotics provides a great place for probiotics to thrive, the population of these good bacteria is preserved.[3]


  Oral Microbiota in Health and Disease Top


The normal microbiota of the mouth is responsible for the two commonest diseases in man—dental caries and the periodontal diseases.[7] Our knowledge regarding the microbial community that colonizes the human oral cavity is expanding at a rapid pace. To detect and quantify the products of microbial metabolism, new worldwide initiatives such as sequencing of the human microbiome along with rapid advances in metabolomics are contributing to a better comprehension of the role of symbionts in health and disease.[8] The microbiota colonizing the oral cavity is composed of diverse groups of microbial species, each one possessing its specific nutritional and physicochemical requirements. Although fungi, viruses, protozoa, and archaea have been found, bacteria are the most predominant microorganisms present in the oral cavity. The abundance of several genera, including Lactobacillus, Megasphaera, Olsenella, Scardovia, Shuttleworthia, and Streptococcus, was significantly increased in dentinal caries.[9] The genera Streptococcus, Granulicatella, and Actinomyces were significantly increased in children with severe early childhood caries.[9] Some health-associated bacteria have been shown to be antagonistic to oral pathogens. For example, Streptococcus salivarius strain K12 produces a bacteriocin, which inhibits the growth of Gram-negative species, which are associated with periodontitis and halitosis in vitro, and has been shown to have beneficial effects on halitosis in vivo. So, in this way, we can utilize synbiotics in improving oral health.


  Dynamics of Colonization of Synbiotics Top


An essential requirement for a microorganism to be an oral probiotic is its ability to adhere and to colonize on the surfaces of oral cavity. There are many variables that can affect the permanence of new bacterial strains in the oral cavity. The new bacteria enter in a very complex system of interactions with the resident flora. At least five types of interaction have been described: competition for nutrients, synergy, antagonism, neutralization of virulence factors, and interference with the bacterial signaling systems (quorum sensing).

The competition for nutrients and essential elements to consider for the survival of the probiotic is closely dependent on the availability of nutrients that can be used by different strains. Prebiotics such as fructans, maltodextrins, fructo-oligosaccharides, and galacto-oligosaccharides are mostly the components of our diet that become one of the critical elements for the distribution and composition of the oral microbiome.[10]


  Immunomodulation and Features of Synbiotics in Oral Cavity Top


The combined effect of probiotics with prebiotics results in the modulation of the metabolic activity with the preservation of the biostructure, development of beneficial microbiota, and inhibition of potential pathogens present in the oral cavity.

Gourbeyre et al. in 2011 stated that synbiotics improved the immune function and stimulated appropriate immunomodulatory cells.[11] Synbiotics stimulate the host immune response by increasing the phagocytic activity, synthesis of IgA, activation of T and B lymphocytes, and alteration of physicochemical conditions by decreasing pH. Host immune response in the intestine is different from that in the oral cavity as it is not an organ of mucosal associated lymphoid tissue. Traditionally, probiotics were developed to alter gut microflora. As oral cavity is the foremost part of gastro intestinal tract, it is conceivable for probiotics to influence the oral microflora.

The host immune component and reactions are important considerations for synbiotic therapy of the intestine and oral cavity. Probiotic bacteria are incorporated into microfold cells in Peyer’s patches in the intestine, which is a main component of gut-associated lymphoid tissues, and digested to form active antigens. T-cell and B-cell functions are stimulated by several cytokines, which are produced by activated Peyer’s patches. Synbiotics in the intestinal tract are likely to activate both innate immunity and acquired immunity. Conversely, the oral cavity is not an immune organ, and a phenomenon such as direct antigen presentation to adaptive immune cells does not occur. It was found that children who were oral Lactobacilli carriers had similar Lactobacilli in their feces (Caufield et al., 2015).[11] Hence, it appears that the intestinal colonization of Lactobacilli is transmitted though the oral cavity, which may provide simultaneous synbiotic activity in the oral cavity and intestine.[12]


  Synbiotic Selection Criteria for Oral Diseases Top


The important aspect to be taken into consideration when composing a synbiotic formula should be a selection of an appropriate probiotic and prebiotic, exerting a positive effect on the host’s health when used separately. The determination of specific properties to be possessed by a prebiotic to have a positive effect on the probiotic seems to be the most suitable approach.[4] A prebiotic should selectively stimulate the growth of microorganisms, having a beneficial effect on health, with simultaneous limited stimulation of other microorganisms.[3] Studies of oral prebiotics are limited. Sugars and dietary fiber have been considered to be prebiotics for intestinal bacteria (Gibson and Roberfroid, 1995). However, this could not be the case for the oral environment, as the presence of sugars increases the risk of dental caries.

Bifidobacterium or Lactobacillus genus bacteria with fructo-oligosaccharides in synbiotic products are the most well-accepted combination. Other synbiotic combinations that can be used are depicted in [Figure 2]. Out of these synbiotic combinations, xylitol and inulin as prebiotics could be utilized in oral cavity.[4]
Figure 2: Examples of synbiotics used in human nutrition (Markowiak and Slizewska, 2017)

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  Therapeutic Application of Synbiotics in Oral/Dental Health Top


Role in caries prevention

The use of synbiotics presents a novel ecological-based caries preventive strategy. Bijle et al. (2020) evaluated the effect of a synbiotic combination of probiotic L. acidophilus NCFB 1748 with glucomannan hydrolysate, which is a polysaccharide to stimulate the growth of probiotic microorganisms. They concluded that the consumption of glucomannan hydrolysate as a prebiotic can potentially improve the ecology of the mouth by promoting the growth of beneficial bacteria and suppressing pathogens.[12] Another clinical trial was carried out to promote the growth of healthy arginolytic bacteria (S. sanguinis and S. gordonii) by prebiotics and concurrently enrich the growth of probiotics L. rhamnosus Gorbach Goldin (GG) for enduring oral colonization. Arginine has been used as an oral prebiotic to reinforce the growth of alkalogenic health-promoting bacteria—Streptococcus sanguinis, Streptococcus parasanguinis, and Streptococcus gordonii, with a subsequent inhibition of the cariogenic bacterium—Streptococcus mutans. Moreover, it enhances the antimicrobial and remineralization effects of fluoride. However, prolonged use of arginine may facilitate plaque alkalization, promoting the growth of oral anaerobes such as Porphyromonas gingivalis. The use of L-arginine as a prebiotic enhances the growth of the probiotic—L. rhamnosus GG in a dose-dependent manner. L. rhamnosus GG has been associated with coaggregation of S. mutans, preventing their adherence to the tooth surfaces, bactericidal effects on S. mutans, reduced production of insoluble extracellular polysaccharides in biofilm formation, and reduction of salivary counts of S. mutans.[13] Overall, the synbiotic therapy could serve as an oral biofilm modifier and can be an effective anti-caries treatment, especially for high caries-risk patients by utilizing the much-needed ecological-based caries preventive approach. For daily use, synbiotics can be integrated into mouth rinses or dentifrice. The twice daily use of the synbiotics might help maintain ecological homeostasis in patients after meal consumption, whereby the low plaque pH and its detrimental cariogenic effects can be prevented. Apart from anti-caries benefits, this combination might have some potential systemic benefits, as both L-arginine and the probiotic L. rhamnosus GG have demonstrated systemic benefits individually.[14] So synbiotics can play promising role in caries preventive protocols.

Role in oral candidiasis

Most frequent fungal infection in the oral cavity is generally caused by Candida albicans.[10] Probiotic Lactobacilli co-aggregate with Candida and produce antimicrobial substances that have a direct growth inhibitory effect on Candida.[12] Lactobacilli produce lactic acid that inhibits the metabolic activity of Candida species. Lactobacilli strains are able to metabolize xylitol, which is an emerging oral prebiotic.[15] Xylitol is considered a preferable fermentable carbohydrate for several important strains of bacteria, which reduces the growth of Candida albicans through competition for growth medium and adhesive areas. It promotes the growth of health-promoting probiotic bacteria such as Lactobacilli.[15] Maleszka and Schneider (1982) showed that the proper growth of C. albicans is inhibited by the presence of xylitol. Thus, if appropriate prebiotics are administered simultaneously, then synbiotic therapy may suppress the development of oral candidiasis.[12]

Role in periodontitis

Periodontitis is a chronic inflammatory disease that leads to the destruction of supporting tissues of the tooth. Aggressive form of the disease commonly affects systemically healthy individuals who are younger than 30 years.[16] The most common and conventional treatment for aggressive periodontitis is scaling and root planning (SRP) under the coverage of systemic antibiotics. But overuse and misuse of antibiotics over time have led to the emergence of drug-resistant microorganisms. The recent trend is the usage of synbiotics in managing such antibiotic resistant oral diseases. Probiotics such as Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus, and Lactobacillus sporogenes are used in the management of periodontitis. Murugesan et al. in 2018 concluded that the coadministration of synbiotic along with standard therapy is more efficacious than SRP along with doxycycline in the treatment of aggressive periodontitis. They also concluded that synbiotics are safe and could be used in the routine management of aggressive periodontitis. It has an anti-inflammatory and antimicrobial property, which prevents and safeguards against the destruction of periodontal attachment apparatus and loss of alveolar bone.[17] Bazyar et al. in 2020 observed that synbiotic supplementation with nonsurgical periodontal therapy was beneficial in improving inflammatory, antioxidant, and periodontal status in type 2 diabetes mellitus patients with chronic periodontitis.[18]

Role in orthodontic treatment

Orthodontic procedures are intended to establish a healthy, functional, and appealing occlusion that is in balance with facial esthetics. When orthodontic appliances are involved, they are associated with various oral hygiene challenges including plaque traps, continued biofilm accumulation leading to inflammatory changes, gingival bleeding, and enamel decalcification.[17],[18] Synbiotics can create a cariostatic effect by fighting the bacteria that cause tooth decay.[19] The administration of synbiotics for a longer duration may be required to demonstrate any potential for clinical improvements.

Risks associated with synbiotics

Occurrences of probiotic causing harm are rare, but the most commonly encountered side effect is gastrointestinal distress such as bloating. S. boulardii and Lactobacillus GG have been reported to accelerate the complications in specific patient groups, especially the immune-compromised subjects. Pregnant women, newborns, and elderly people are at higher risk of potential probiotic infection because they are immune-compromised. Excessive intake of prebiotics especially oligosaccharides such as FOS, GOS, etc. causes abdominal discomfort such as bloating and distension, as well as significant levels of flatulence.[20]


  Conclusion Top


Synbiotics have established a foundation that could be used to develop oral healthcare products without disrupting the balance of a healthy oral environment. The careful selection of the synbiotic to be ingested for a particular disease is essential, and mode and timing of administration could be crucial. There exists a sufficient knowledge base for major and minor risk factors in the administration of synbiotics to prevent intestinal conditions but, for oral applications, it is clearly more distant. Now it will also be a challenge to ensure that modes of delivery are developed that provide sufficient retention and exposure times in the mouth to allow probiotics to colonize the plaque and prebiotics to enter into plaque or mucosal biofilms to influence microbial metabolism within them. Several concerns should be considered when future studies are addressed, to obtain not only reliable results but also treatment feasibility to be applied and practically followed.

Future aspects

Several synbiotics have been proposed for the prevention of oral diseases; however, their eligibility for classification as true synbiotics needs to be carefully addressed. Because of a lack of clinical studies on synbiotics for the prevention of oral diseases, evidence on their preventive potential is weak. Future studies are needed to examine the potential synbiotic activity against oral pathogens. As there is no synbiotic consumer product for oral diseases identified in the literature, there is a need for highlighting the commercial development and optimal dosage of probiotics and prebiotics, and treatment duration for future synbiotics research.[12]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[25]



 
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Bijle MN, Neelakantan P, Ekambaram M, Lo EC, Yiu CK Effect of a novel synbiotic on Streptococcus mutans. Sci Rep 2020;10:1-9.  Back to cited text no. 14
    
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Kojima Y, Ohshima T, Seneviratne CJ, Maeda N Combining prebiotics and probiotics to develop novel synbiotics that suppress oral pathogens. J Oral Biosci 2016;58:27-32.  Back to cited text no. 15
    
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Murugesan G, Sudha KM, Subaramoniam MK, Dutta T, Dhanasekar KR A comparative study of synbiotic as an add-on therapy to standard treatment in patients with aggressive periodontitis. J Indian Soc Periodontol 2018;22:438-41.  Back to cited text no. 17
    
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