http://www.taamirplus.com/probiotics-benefits/

Probiotics: A Double-edged Sword in Caries Prevention

A/Prof Hsu Chin-Ying, Stephen Faculty of Dentistry, National University of Singapore

http://myphilippinedentist.com/tooth-decay.htm

Probiotics and Oral Health Probiotics: “live microorganisms which when administered in adequate amounts

confer a health benefit on the host” (WHO, 2002)

Proven safety and gastrointestinal health benefits (Butel, 2014)

Increasing interest in oral health applications with focus on dental caries prevention (Devine and Marsh, 2009)

Overview of oral health and disease:

http://sigma-implants.com/content/33-application_of_individual_abutments

PATHOGENIC BACTERIA IN BACTERIAL

BIOFILM

BENEFICIAL BACTERIA

IN BACTERIAL

BIOFILM PERIODONTAL DISEASES

http://imaginesmiles.blogspot.sg/2011/11/gum-disease-can-increase-time-it-takes.html

DENTAL CARIES

http://www.dentalnotebook.com/caries-lesion-classification-g-v-black/

PROBIOTICS

http://www.students4bestevidence.net/tag/systematic-reviews/

Ecological Plaque Hypothesis in Caries Etiology

Caries: localized destruction of dental hard tissues by acidic by-products from bacterial fermentation of dietary carbohydrates (Selwitz et al., 2007)

Hypothesis first proposed by P.D. Marsh in 1991 (Marsh, 1991) Dynamic relationship – environmental change produces a shift in the

balance of resident microflora, thereby favoring demineralization (Marsh, 1994)

Mutans streptococci (MS) and Lactobacilli (LB) as major groups of cariogenic bacteria

(Marsh, 1994)

Extended Caries Ecological Hypothesis Incorporation of the microbiological, biochemical, ecological and

clinical perspectives Environmental acidification as main determinant of phenotypic and

genotypic changes in microflora during caries Non-MS bacteria associated with caries include Lactobacillus spp.,

Bifidobacterium spp., Prevotella spp. and Propionibacterium spp. (Takahashi and Nyvad, 2011)

(Takahashi and Nyvad, 2011)

Probiotics and Dental Caries

Lactic acid bacteria (LAB) Lactobacillus spp. and Bifidobacterium spp. most commonly studied

Natural inhabitants of oral cavity; generally safe (Chouraqui et al., 2008)

In particular, ability of Lactobacilli (LB) to reduce S. mutans has attracted lots of attention (Russell and Ahmed, 1978)

HOWEVER, LAB are acidogenic and aciduric themselves Current obstacles:

Limited clinical studies Widely different study designs and target populations Incongruous findings Lack of knowledge on sustainability of effects

Randomised controlled trial (in vivo) studies into LAB effect on S. mutans

Mixed results

Multiple multifactorial

LB cariostatic mechanisms??

Research on Probiotics Use Against Dental Caries

Studies done in vitro on effects of LB and their products on S. mutans

Mixed results

LB cariostatic

mechanisms highly dependent on specific probiotic strains and target oral pathogens??

Research on Probiotics Use Against Dental Caries

Effects of LB on

caries development

Promising results

but limited validation studies done

Is early intervention crucial??

Are effects sustainable??

Research on Probiotics Use Against Dental Caries

Ability of probiotics to adhere to epithelium an Important factor

Different LAB strains show different adhesion properties

Research on Probiotics Use Against Dental Caries

Research on Probiotics Use Against Dental Caries

Classic criterion

for a successful probiotics agent: ability to colonize in intestine and oral cavity (Michail, 2005)

Limited studies

Yakult® Study Rationale

http://yakult.com.sg/l-casei-strain-shirota/

Introduced in 1935

Widespread global popularity

108 CFU/mL live L. casei Shirota strain (LcS)

Documented safety and gastrointestinal health benefits

Limited research on oral applications

Acidic drink

High in sugar (~17.9g/100g) classified “HIGH” by UK Food Standards; ~88% of which is sucrose

L. casei is itself associated with caries

Yakult® Study

http://yakult.com.sg/l-casei-strain-shirota/

Introduced in 1935

Widespread global popularity

108 CFU/mL live L. casei Shirota strain

Documented safety and gastrointestinal health benefits

Limited research on oral applications

Acidic drink

High in sugar (~17.9g/100g) classified “HIGH” by UK Food Standards; ~88% of which is sucrose

L. casei is itself associated with caries

Yakult® Study Design

Yakult® Study Conclusions

Short-term probiotic consumption may be transiently cariostatic in individuals with higher baseline plaque acidogenicity, but cariogenic in lower-risk individuals

Proper individualized caries risk assessment critical prior to probiotics

applications in caries prevention Unconventional LcS cariostatic mechanism involving S. mutans

gene regulation Findings corroborate with extended caries ecological hypothesis

Balance between probiotic’s cariostatic capabilities and its own

acidogenicity

Probiotics in Caries Prevention – An Enigma

Further investigations to validate use of probiotics in oral health applications

Microbiome studies are warranted to study ecology shifts during health and disease and role of probiotic bacteria

Exploring the oral-systemic-gut link in dental caries

References

World Health Organization (2002). Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food, April 30 and May 1, 2002, London, Ontario, Canada.

Butel MJ (2014). Probiotics, gut microbiota and health. Med Mal Infect 44:1-8.

Devine DA, Marsh PD (2009). Prospects for the development of probiotics and prebiotics for oral applications. J Oral Microbiol 1;1.

Marsh PD (1991). Sugar, fluoride, pH and microbial homeostasis in dental plaque. Proc Finn Dent Soc 87:515-525.

Marsh PD (1994). Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res 8(2):263-271.

Selwitz RH, Ismail AI, Pitts NB (2007). Dental caries. Lancet 369:51-59.

Takahashi N, Nyvad B (2011). The role of bacteria in the caries process: ecological perspectives. J Dent Res 90:294-303.

Bosch M, Nart J, Audivert S, Bonachera MA, Alemany AS, Fuentes MC, Cuñé J (2012). Isolation and characterization of probiotic strains for improving oral health. Arch Oral Biol 57(5):539-49.

Ahola AJ, Yli-Knuuttila H, Suomalainen T, Poussa T, Ahlstrom A, Meurman JH et al. (2002). Short-term consumption of probiotic-containing cheese and its effect on dental caries risk factors. Arch Oral Biol 47(11):799-804.

Aminabadi NA, Erfanparast L, Ebrahimi A, Oskouei SG (2011). Effect of chlorhexidine pretreatment on the stability of salivary lactobacilli probiotic in six- to twelve-year-old children: a randomized controlled trial. Caries Res 45(2):148-154.

Busscher HJ, Mulder AF, van der Mei HC (1999). In vitro adhesion to enamel and in vivo colonization of tooth surfaces by Lactobacilli from a bio-yoghurt. Caries Res 33(5):403-404.

Caglar E, Sandalli N, Twetman S, Kavaloglu S, Ergeneli S, Selvi S (2005). Effect of yogurt with Bifidobacterium DN-173 010 on salivary mutans streptococci and lactobacilli in young adults. Acta Odontol Scand 63(6):317-320.

Caglar E, Cildir SK, Ergeneli S, Sandalli N, Twetman S (2006). Salivary mutans streptococci and lactobacilli levels after ingestion of the probiotic bacterium Lactobacillus reuteri ATCC 55730 by straws or tablets. Acta Odontol Scand 64(5):314-318.

References Caglar E, Kavaloglu SC, Kuscu OO, Sandalli N, Holgerson PL, Twetman S (2007). Effect of chewing gums containing xylitol or probiotic

bacteria on salivary mutans streptococci and lactobacilli. Clin Oral Investig 11(4):425-429.

Caglar E, Kuscu OO, Cildir SK, Kuvvetli SS, Sandalli N (2008a). A probiotic lozenge administered medical device and its effect on salivary mutans streptococci and lactobacilli. Int J Paediatr Dent 18(1):35-39.

Caglar E, Kuscu OO, Selvi Kuvvetli S, Kavaloglu Cildir S, Sandalli N, Twetman S (2008b). Short-term effect of ice-cream containing Bifidobacterium lactis Bb-12 on the number of salivary mutans streptococci and lactobacilli. Acta Odontol Scand 66(3):154-158.

Chouraqui JP, Grathwohl D, Labaune JM, Hascoet JM, de Montgolfier I, Leclaire M et al. (2008). Assessment of the safety, tolerance, and protective effect against diarrhea of infant formulas containing mixtures of probiotics or probiotics and prebiotics in a randomized controlled trial. Am J Clin Nutr 87(5):1365-1373.

Chuang LC, Huang CS, Ou-Yang LW, Lin SY (2011). Probiotic Lactobacillus paracasei effect on cariogenic bacterial flora. Clin Oral Investig 15(4):471-476.

Hillman JD, McDonell E, Cramm T, Hillman CH, Zahradnik RT (2009). A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries. Journal of applied microbiology 107(5):1551-1558.

Jindal G, Pandey RK, Agarwal J, Singh M (2011). A comparative evaluation of probiotics on salivary mutans streptococci counts in Indian children. Eur Arch Paediatr Dent 12(4):211-215.

Keller MK, Hasslof P, Stecksen-Blicks C, Twetman S (2011). Co-aggregation and growth inhibition of probiotic lactobacilli and clinical isolates of mutans streptococci: an in vitro study. Acta Odontol Scand 69(5):263-268.

Lang C, Bottner M, Holz C, Veen M, Ryser M, Reindl A et al. (2010). Specific Lactobacillus/Mutans Streptococcus co-aggregation. Journal of dental research 89(2):175-179.

Lexner MO, Blomqvist S, Dahlen G, Twetman S (2010). Microbiological Profiles in Saliva and Supragingival Plaque from Caries-Active Adolescents Before and After a Short-Term Daily Intake of Milk Supplemented with Probiotic Bacteria-A Pilot Study. Oral Hlth Prev Dent 8(4):383-388.

References Lima LM, Motisuki C, Spolidorio DMP, Santos-Pinto L (2005). In vitro evaluation of probiotics microorganisms adhesion to an artificial caries

model.

Eur J Clin Nutr 59(7):884-886.

Lodi CS, Manarelli MM, Sassaki KT, Fraiz FC, Delbem AC, Martinhon CC (2010). Evaluation of fermented milk containing probiotic on dental enamel and biofilm: in situ study. Arch Oral Biol 55(1):29-33.

Michail S (2005). The Mechanism of Action of Probiotics. PRACTICAL GASTROENTEROLOGY.

Montalto M, Vastola M, Marigo L, Covino M, Graziosetto R, Curigliano V et al. (2004). Probiotic treatment increases salivary counts of lactobacilli: a double-blind, randomized, controlled study. Digestion 69(1):53-56.

Nase L, Hatakka K, Savilahti E, Saxelin M, Ponka A, Poussa T et al. (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):412-420.

Nikawa H, Makihira S, Fukushima H, Nishimura H, Ozaki Y, Ishida K et al. (2004). Lactobacillus reuteri in bovine milk fermented decreases the oral carriage of mutans streptococci. Int J Food Microbiol 95(2):219-223.

O'Connor EB, O'Riordan B, Morgan SM, Whelton H, O'Mullane DM, Ross RP et al. (2006). A lacticin 3147 enriched food ingredient reduces Streptococcus mutans isolated from the human oral cavity in saliva. Journal of applied microbiology 100(6):1251-1260.

Petersson LG, Magnusson K, Hakestam U, Baigi A, Twetman S (2011). Reversal of primary root caries lesions after daily intake of milk supplemented with fluoride and probiotic lactobacilli in older adults. Acta odontologica Scandinavica 69(6):321-327.

Russell C, Ahmed FI (1978). Interrelationships between lactobacilli and streptococci in plaque formation on a tooth in an artificial mouth. The Journal of applied bacteriology 45(3):373-382.

Samot J, Lebreton J, Badet C (2011). Adherence capacities of oral lactobacilli for potential probiotic purposes. Anaerobe 17(2):69-72.

Singh R, Damle SG, Chawla A (2011). Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifidobacterium lactis Bb12 and Lactobacillus acidophilus La5. Acta odontologica Scandinavica 69(6):389-394.

References Soderling EM, Marttinen AM, Haukioja AL (2011). Probiotic lactobacilli interfere with Streptococcus mutans biofilm formation in vitro. Curr

Microbiol 62(2):618-622.

Stamatova I, Kari K, Vladimirov S, Meurman JH (2009). In vitro evaluation of yoghurt starter lactobacilli and Lactobacillus rhamnosus GG adhesion to saliva-coated surfaces. Oral Microbiol Immun 24(3):218-223.

Stecksen-Blicks C, Sjostrom I, Twetman S (2009). Effect of long-term consumption of milk supplemented with probiotic lactobacilli and fluoride on dental caries and general health in preschool children: a cluster-randomized study. Caries research 43(5):374-381.

Tahmourespour A, Kermanshahi RK (2011). The effect of a probiotic strain (Lactobacillus acidophilus) on the plaque formation of oral Streptococci.

Bosnian journal of basic medical sciences / Udruzenje basicnih mediciniskih znanosti = Association of Basic Medical Sciences 11(1):37-40.

Tanzer JM, Thompson A, Lang C, Cooper B, Hareng L, Gamer A et al. (2010). Caries inhibition by and safety of Lactobacillus paracasei DSMZ16671. J Dent Res 89(9):921-926.

Teanpaisan R, Piwat S, Dahlen G (2011). Inhibitory effect of oral Lactobacillus against oral pathogens. Letters in applied microbiology 53(4):452-459.

Wei H, Loimaranta V, Tenovuo J, Rokka S, Syvaoja EL, Korhonen H et al. (2002). Stability and activity of specific antibodies against Streptococcus mutans and Streptococcus sobrinus in bovine milk fermented with Lactobacillus rhamnosus strain GG or treated at ultra-high temperature. Oral Microbiol Immun 17(1):9-15.

Westbroek ML, Davis CL, Fawson LS, Price TM (2010). Interactions of Lactobacilli with pathogenic Streptococcus pyogenes. Infect Dis Obstet Gynecol 2010(289743.

Yang Y, Chen W, Zhang H, Tang J (2008). [Probiotic characteristics of Lactobacilus plantarum HO-69 applied in oral cavity]. Hua Xi Kou Qiang Yi Xue Za Zhi 26(5):482-485, 489.

Zahradnik RT, Magnusson I, Walker C, McDonell E, Hillman CH, Hillman JD (2009). Preliminary assessment of safety and effectiveness in humans of ProBiora3, a probiotic mouthwash. J Appl Microbiol 107(2):682-690.

Acknowledgements Many thanks to the following members of the Cariology research

team of Faculty of Dentistry, National University of Singapore involved in this study: Ms. Cai Meijin Dr. Carolina Un Lam Dr. Jared Lim Jin Keong, Dr. Mok Li Qian Dr. Seow Hong Kai Dr. Benjamin Yap Baojie

Many thanks to the following collaborators for their guidance and supervision: A/Prof. Eric Yap Peng Huat Dr. Ng Ching Ging Dr. Joel Khoo Tuo Sheng

This study was partly supported by NMRC grant R-221-000-059-511 and UROP grant of Faculty of Dentistry, NUS