Probiotics

Background Information On The Mouth/ Caries

Key organisms within the oral microbiota include Streptococci, an aerobic bacteria – mainly in the forms S. mutans and S. salivarius, Lactobacillus, which can survive in both aerobic and anaerobic conditions. The occurrence of caries (and also periodontal diseases, halitosis, gingivitis and even infections removed from the site of the primary oral infection) can be attributed to an inbalance in the ecosystem i.e. microbial unbalance in the biofilms formed in the oral cavity. Probiotics are bacteria which can competitively exclude cariogenic strains of bacteria by coaggregating i.e. binding to it and incorporating itself into the biofilm in place of the resident native oral flora. (Thomas, 2009)

Introduction

Probiotics are live microorganisms (in most cases, bacteria) that are similar to beneficial microorganisms found in the human gut. They are also called "friendly bacteria" or "good bacteria." Probiotics are available to consumers mainly in the form of dietary supplements and foods, such as fortified foods (yoghurt, cheese), lozenges, rinse solutions, and capsule lichids. Administration of probiotics is best done after flossing i.e. after any brushing and aseptic mouth rinses.

Oral probiotic lozenges are beneficial to anyone who is at risk for plaque accumulation, gum inflammation, cavities, periodontal disease, or any other oral infections

In the case of probiotics in the oral cavity, the bacteria strain used is usually a Lactobacillus anti-caries bacteria that causes streptococcus mutans, a cariogenic bacterium, to clump together. In terms of general probiotics, bifidobacteria may also be used; these bacteria are non-pathogenic and non-toxigenic. (Matsumoto et al, 2005)

Many other strains of bacteria, namely streptococci, lactobacilli and bifidobacteria have also been used for probiotic therapy. Although rates of success vary, the mechanism and general result is the same – inhibition of s. mutans, reduced yeast counts, reduced levels of cariogenic pathogens. (Thomas, 2009)

Streptococcus Mutans
Fig. 1 - Streptococcus Mutans
(Probiotic Discoveries Oragenics, 2009)


lactobacillus acidophilus
Fig. 2 - Lactobacillus
( Kenneth Todar, 2009 )


Definitions of Probiotics

Experts have debated how to define probiotics. One widely used definition, developed by the World Health Organization and the Food and Agriculture Organization of the United Nations, is that probiotics are "live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host." (Microorganisms are tiny living organisms—such as bacteria, viruses, and yeasts—that can be seen only under a microscope.)

  • The term 'probiotics' is defined as 'living microorganisms that exhibit beneficial effects for health based on improvement of balance of indigenous microbiota.' (Nobuko et al, 2006)
  • Probiotics are bacterial cultures or living microorganisms which, upon ingestion in certain numbers, exert health benefits beyond inherent general nutrition and support a good and healthy intestinal bacterial flora. (Mokeem, 2007)
  • “Probiotic,” as used here, means that mechanisms are employed to selectively remove only the (odonto) pathogen while leaving the remainder of the oral ecosystem intact. (Anderson, 2006)
  • Probiotics are live microorganisms which,when administered in adequate amounts, confer a health benefit for the host (Food and Agricultural Organization of the UN and International Scientific Association for Probiotics and Prebiotics)
  • Probiotics provide a natural approach to replacing the unbalanced flora with a pool or single strain that may out-compete the harmful organisms and cooperate within the normal microbial community (Thomas, 2009)

Mechanism of Function

Probiotic strains show coaggregation abilities with pathogenic strains (Twetman et al, 2009, p.284-88). Probiotics therefore function through competing with or directly inhibiting cariogenic bacterioorganisms (Marsh & Devine, 2009)

2 distinct but complementary pathways are engaged:
  1. Replacement of supplemental pathogenic flora enhanced by antibiotic/chemical activity
  2. Increase/control of local/systemic immune protection (Thomas, 2009)

Relation of Dental Caries to Probiotics

Dental caries are formed through interactions between acid-producing bacteria and fermentable carbohydrates. Probiotics provide a means to inhibit the acid-producing bacteria and in doing so, decrease the occurrence of caries. There are many ways to change the oral ecology, among them bacteriotherapy and sugar substitution.


Probiotics - Whole Bacteria Replacement Therapy

Also known as replacement therapy, competitive exclusion, biotherapeutics, probiotics have been shown to aid in various oral diseases – dental caries, gingivitis, halitosis, oral candidiasis, periodontal disease, xerostomia, oral manifestations of skin and systemic diseases etc.

Microbial ecological change may work as a mechanism for preventing dental disease. Pathogenic members (the more cariogenic ones) of the microbiota may also be investigated, and whole bacteria replacement therapy may be used to reduce their cariogenic effects.

In summary, harmless bacteria may be used to combat infections by displacing pathogenic microorganisms.

Relatively avirulent strains of streptococcus mutans bacteria may be introduced to occupy the same ecological niche in plague as their cariogenic counterparts. (Caglar et al, 2005)

Biofilm_Probiotics
Fig. 3 - Effects of probiotics in the oral cavity

  • Development of an inexpensive targeting molecule that will attach itself only to the organism of interest, in this case streptococcus mutans (S mutans). Once the targeting molecule is perfected, a killer molecule is optimized and 'chained' to the targeting molecule. The combined unit then selectively eliminates the infection of interest
  • This method serves to eliminate pathogens and preclude the regrowth of the original infection
  • There is also compelling evidence from trials that once the bacterial ecosystem is free of S mutans, it is difficult to reintroduce the organisms (a competitive inhibition situation)
  • However, probiotics do not address other pathogens which may be involved in the disease process (Anderson, 2006)


Supporting Studies & Experiments on Whole Bacteria Replacement Therapy

  1. Nearly 600 pre-school children, over a period of 7 months were given both probiotic and placebo milk products
  2. Statistically significant differences were found in the development of caries between both groups of children
  3. Children in active group developed caries in 13 new teeth and 6 new initial carious lesions, while the corresponding figures in the placebo group were 16 and 8.
  4. However, the clinical effect may be considered minimal, and the use of fluoride is more cost-effective
(Sullivan and Nord, 2002)

Other studies done with Lactibacillus rhamnosus GG, L. casei and L. reuteri showed that the Lactobacilli strains were associated with a temporary reduction in S. mutans, implying that continued administration was necessary for long term benefit. (Thomas, 2009) Another study by Montalto et al showed that oral administration of Lactobacillus could reduce the salivary counts of S. mutans compared with placebo, but the reduction was only marginal, suggesting also the need for constant surveillance in order for treatment to be effective. (Montalto et al, 2002)

Another study in which a group of children was fed either milk with L. rhamnosus or control milk without the bacterial strain showed that the LGG milk i.e. the one with the lactobacilli, was beneficial in reducing caries occurance, especially in 3- to 4-year-old children. (Näse et al, 2001) Caries are known to correlate well with the number of oral lactobacilli in children. (Granath et al, 1994)

Lactate-dehydrogenase deficient mutants may also affect acid production by Streptococcus Mutans, reducing their cariogenecity. Glucan-binding lectin is important in the adherence of S. Mutans to tooth surfaces and may be negatively transcripted by the gcrR gene, which encodes a transcriptional regulatory protein. Insertion-deletion mutations may be present in this gene in an LDH-deficient S. Mutans mutant. This may therefore result in an overexpression of glucan-binding lectin, and hence higher adherence to teeth but lower-level acid production and strong colonization potential. (Sun et al, 2009)

In vitro study of coaggregation between probiotic bacteria and cariogenic bacteria

Objective: To evaluate the in vitro abilities of probiotic bacteria derived from consumer products to coaggregate i.e. when genetically distinct bacteria adhere to each other (National Institute of Dental and Craniofacial Research, 2006) with caries-associated mutans streptococci

Material and methods:
  1. Lactobacillus strains were cultivated under anaerobic conditions for 24 hours
  2. 4 strains of human streptococci were similarly grown
  3. A GI pathogen, E. Coli, was aerobically cultivated and suspended in saline
  4. Probiotic strains were characterized to confirm their identity
  5. Coaggregation was determined by spectrophotometry in mixtures, expressed as the aggregation ratio (%)

Results:
All probiotic strains showed coaggregation abilities with the oral pathogens and the results were strain specific and dependent on time. S. mutans GS-5 exhibited a significantly higher ability to coaggregate with all the probiotic strains than the other mutans streptococci and E. coli.

Interpretation of Results:
The results prove the mechanism of function of the probiotic bacteria, in that the bacteria coaggregates with the cariogenic streptococcus mutans. Also, the findings show that S. mutans GS-5 has the highest ability to coaggregate with s. mutans, suggesting that it is probably the most suitable for probiotic purposes i.e. in inhibiting the function of s. mutans by coaggregation.


Probiora 3
By Dr Richard Hillman ( Orgenics, 2009)

  • Discovery of a mixture of 3 strains of beneficial bacteria: S. oralis, S. uberis and S. rattus (first 2 for periodontal health and the 3rd for prevention of caries)
  • These bacteria provide a balance between healthy oral microflora and disease-causing bacteria
  • Streptococcus rattus is very closely related to S. mutans and hence it will compete with S. mutans for nutrients and attachment sites on the tooth surface
  • S. rattus is deficient in its ability to produce lactic acid and thus is less harmful to the enamel than S. mutans
  • Product “Probiora 3” – mixture of 3 natural bacteria for maintenance of dental health

Recent Developments
Evidence suggests that there may also be other subtle mechanisms by which probiotics function:
  • Modulation of the mucosal immune system
  • Promote growth of beneficial microorganisms that comprise part of the resident microbiota. (Marsh & Devine, 2009)

Interesting Innovations

  • Probiotic chewing gum to reduce occurrance of caries; also serves purpose of reducing halitosis via probiotic effects (Woman's Passion, 2006)
Probiotic Chewing Gum
  • Dietary probiotic supplements to reduce occurrance of caries
Probiotic Dietary Supplements


References

Anderson MH, Shi W (2006). A probiotic approach to caries management. Pediatric Dentistry, 28(2), 151-153

Caglar, E., Kargul, B. & Tanboga, I. (2005). Bacteriotherapy and probiotics' role on oral health. Oral Dis. 2005 May;11(3):131-7.

Granath, L., Cleaton-Jones, P., Fatti, L. P. & Grossman. (1994). Salivary lactobacilli explain dental caries better than salivary mutans streptococci in 4-5- year-old children. Scand J Dent Res, 102:319–323.

Kenneth Todar (2009). The Microbial World. Retrieved Nov 28, 2009 from http://textbookofbacteriology.net/themicrobialworld/NormalFlora.html

Marsh, P. D. & Devine, D. A. (2009). Prospects for the development of probiotics and prebiotics for oral applications. [Electronic version]. Journal of Oral Microbiology, Vol 1 (2009) incl Supplements.

Matsumoto, M., Tsuji, M., Sasaki, H., Fujita, K., Nomura, R., Nakano, K., Shintani, S. & Ooshima, T. (2005). Cariogenicity of the Probiotic Bacterium Lactobacillus salivarius in Rats. Caries Res, 39:479-483


Mokeem, Sameer A. (2007). The synergism of probiotics in dentistry. Retrieved 4 Oct, 2009 from http://www.sdsjournal.org/2007/volume-19-number-3/2007-19-3-editorial.html


Montalto, M., Arancio, F., Izzi, D., Cuoco, L., Curigliano, V., Manna, R. & Gasbarrini, G. (2002). Probiotics: history, definition, requirements and possible therapeutic applications. Retrieved Nov 28, 2009 from http://www.biomedexperts.com/Abstract.bme/12402663/Probiotics_history_definition_requirements_and_possible_therapeutic_applications


Näse, L., Hatakka, K., Savilahti, E., Saxelin, M., Pönkä, A., Poussa, T., Korpela, R. & Meurman, J.H. (2001). Effect of Long-Term Consumption of a Probiotic Bacterium, Lactobacillus rhamnosus GG, in Milk on Dental Caries and Caries Risk in Children. Caries Res;35(6):412-20.

Nobuko, M., Tomoko, O., Ken’ichi, H. & Naoki, T. (2006). Do probiotic bacteria improve human oral microbiota? Oral Therapeutics and Pharmacology, 25(3): 61-68. Retrieved from Science Links Japan database

Oragenics (2009). Retrieved Nov 29, 2009 from http://oragenics.com/index-2.html

Probiotic Discoveries Oragenics (2009). Retrieved 4 Oct, 2009 from http://www.oral-probiotics.com/

Sullivan, A. & Nord C. E. (2002). Probiotics in human infections.[Electronic version]. Journal of Antimicrobial Chemotherapy (2002) 50, 625-627

Sun JH, Xu QA, Fan MW. (2009). A new strategy for the replacement therapy of dental caries. Med Hypotheses. 2009 Dec;73(6):1063-1064.

Thomas, J. (2009). Probiotics: The Link Between Beneficial Oral Bacteria and Total Health. Canada: Health Point Press

Twetman, L., Larsen, U., Fiehn, N., Stecksen-Blicks, C. & Twetman, S. (2009). Coaggregation between probiotic bacteria and caries-associated strains: An in vitro study. Acta Odontol Scand, 27:1-5.

Woman's passion (2006). Lifestyle Maganize. Retrieved Nov 29, 2009 from http://www.womanspassions.com/articles/279.html

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