Retrospective Review of Oral Probiotic Therapy

Purpose: There have been many in vitro studies reporting on the efficacy of probiotic bacteria in inhibiting pathogens, and there have been published studies reporting on the inhibitor effects of probiotic bacteria on the salivary levels of bacterial pathogens. However, there have not been but a few studies on the clinical benefits of oral probiotic therapy. Study design: Dental records of 60 patients that were enrolled in an Institutional Review Board approved study were reviewed as to current caries activity status with measurement of the Decayed Missing Filled Teeth index and by Caries Management By Risk Assessment (CAMBRA) determination. The current oral health status was compared to the prior-to-study enrollment status and then analyzed in respect to published national norms.

The data (without any identifiers) had a statistical analysis by a blinded biostatistician. The data was subjected to statistical analysis (Statsgraphic) before and after the probiotic therapy. Results: Of the 53 subjects available for follow up, only 4 had remained caries active with a grand total of 27 carious lesions being detected and subsequently restored in this group. Of the original total of 60 patients with 292 initial carious lesions, after probiotic therapy and dental restoration, 78 total restorations were placed in the subject group over the following three years. Approximately half of these restorations were required in teeth that had initially presented with smaller lesions and had been placed in a “watch” category. Two of the patients that developed further carious lesions had been randomly assigned to the probiotic PerioBalance, while the other two caries active patients were assigned EvoraKids probiotic.

Of the original group of caries active patients, 24 did not present with any further carious involvement. Another 25 could be categorized as caries static, as the restorations required were substantially less than before probiotic therapy had been begun. The F-ratio, which in this case equals 51.3313, is a ratio of the between-group estimate to the within-group estimate. Since the P-value of the F-test is less than 0.05, there is a statistically significant difference between the means of the 4 variables at the 95.0% confidence level. Conclusion: The tested probiotic supplements had a statistically significant effect on the caries experience of the enrolled subjects.

1. Dye BA, Xianfen L, Beltrán-Aguilar ED. Selected Oral Health Indicators in the United States 2005–2008. NCHS Data Brief, no. 96. Hyattsville, MD: National Center for Health Statistics, Centers for Disease Control and Prevention; 2012.

2. National Institute of Health- National Institute of Dental and Craniofacial Research- online March 2019.

3. U.S. Department of Health and Human Services Federal Panel on Community Water Fluoridation. U.S. Public Health Service recommendation for fluoride concentration in drinking water for the prevention of dental caries. Public Health Rep;130:318–31. 2015.

4. Community Preventive Services Task Force. Preventing Dental Caries: Community Water Fluoridation website. https://www.thecommunityguide.org/findings/dental-caries-cavities-community-water-fluoridationExternal. Accessed October 23, 2014.

5. Griffin SO, Jones K, Tomar SL. An economic evaluation of community water fluoridation. J Public Health Dent;61:78–86. 2001.

6. Marinho VCC, Higgins JPT, Logan S, Sheiham A. Fluoride toothpastes for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews. 2003; Issue 1. Art. No.: CD002278. DOI: 10.1002/14651858.CD002278.

7. Griffin SO, Regnier E, Griffin PM, Huntley V. Effectiveness of fluoride in preventing caries in adults. J Dent Res;86:410–5. 2007.

8. Thomson WM. Epidemiology of oral health conditions in older people. Gerodontology 31 Suppl 1:9–16. 2014.

9. Ahovuo-Saloranta A, Forss H, Walsh T, Hiiri A, Nordblad A, Mäkelä M, Worthington HV. Sealants for preventing dental decay in the permanent teeth. Cochrane Database of Systematic Reviews. 2013; Issue 3. Art. No.: CD001830. DOI: 10.1002/14651858.CD001830.pub4.

10. Mejàre I., Lingström P., Petersson L.G., Holm A.K., Twetman S., Källestål C., Nordenram G., Lagerlöf F., Söder B., Norlund A., Axelsson S., Dahlgren H. ,Caries-preventive effect of fissure sealants: a systematic review. Acta Odontol Scand. Dec;61(6):321-30. 2003.

11. Simecek J. W., Diefenderfer K. E., Ahlf R. L. , Ragain J. C. Jr. Dental sealant longevity in a cohort of young U.S. naval personnel. J Am Dent Assoc. Feb;136(2):171-8; quiz 230. 2005.

12. Loesche W.J. Role of Streptococcus mutans in human dental decay. Microbiol Rev; 50(4):353-380 .1986.

13. Loesche W.J. Nutrition and dental decay in infants. Am J Clin Nutr; 41:423-35 .1985.

14. Hamada S. and Slade H.D. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 1980; 44(2):331-84.

15. Sanchez-Perez L. and Acosta-Gıo A.E. Caries risk assessment from dental plaque and salivary Streptococcus mutans counts on two culture media. Arch Oral Biol;46:49–55.2001.

16. Koga T., Oho T., Shimazaki Y. and Nakano Y. Immunization against dental caries. Vaccine; 20:2027–2044. 2002.

17. Loesche W.J., Rowan J., Straffon L.H. and Loos P.J. Association of Streptococcus mutans with human dental decay. Infect Immun; 11:1252- 60. 1975.

18. van Houte J. and Duchin S. Streptococcus mutans in the mouths of children with congenital sucrose deficiency. Arch Oral Biol; 20:771-73. 1975.

19. Islam B., Khan S.N. and Khan A.U. Dental caries: From infection to prevention. Med Sci Monit,; 13(11):RA196-203. 2007.

20. Guarner F., Perdigon G., Coerthier G., Salminen S., Koletzko B. and Morelli L. Should yoghurt cultures be considered probiotic? Br J Nutr; 93:783–786.2005. 21. Koornhof H.J. Probiotics — how functional are they? SAMJ; 94(4):272- 273. 2004.

22. Sheiham A. Dietary effects on dental diseases. Public Health Nutr. Apr;4(2B):569-91. 2001.

23. Silva M., Jacobus N.V., Deneke C. and Gorbach S.L. Antimicrobial substance from a human lactobacillus strain. Antimicrob Agents Chemother; 31:1231–1233. 1987.

24. Isolauri E., Sutas Y., Kankaanpaa P., Arvilommi H. and Salminen S. Probiotics: effects on immunity. Am J Clin Nutr; 73(Suppl. 2): S444– S450. 2001.

25. Meurman J.H. and Stamatova I. Probiotics: contributions to oral health. Oral Diseases; 13:443–451. 2007.

26. Meurman J.H., Antila H. and Salminen S. Recovery of Lactobacillus strain GG (ATCC 53103) from saliva of healthy volunteers after consumption of yoghurt prepared with the bacterium. Microb Ecol Health Dis; 7:295–298.1994.

27. Nase L., Hatakka K., Savilahti E., Saxelin M., Ponka A., Poussa T., Korpela R. and Meurman J.H. Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children. Caries Res; 35:412–420.2001.

28. Ahola A.J., Yli-Knuuttila H., Suomalainen T., Poussa T., Ahlström A., Meurmanb J.H. and Korpela R. Short-term consumption of probiotic-containing cheese and its effect on dental caries risk factors. Arch. Oral Biol; 47:799–804.2002.

29. Nikawa H., Makihira S., Fukushima H., Nishimura H., Ozaki Y. and Ishida K. Lactobacillus reuteri in bovine milk fermented decreases the oral carriage of mutans streptococci. Int J Food Microbiol; 95:219–223.2004.

30. Busscher H.J., Mulder A.F. and van der Mei C.H. In vitro adhesion to enamel and in vivo colonization of tooth surfaces by lactobacilli from a bio-yogurt. Caries Res; 33:403–404.1999.

31. Cildir S. K., Germec D., Sandalli N., Ozdemir F. I., Arun T., Twetman S., Caglar E., Reduction of salivary mutans streptococci in orthodontic patients during daily consumption of yoghurt containing probiotic bacteria. Eur J Orthod. 2009 Aug;31(4):407-11. doi: 10.1093/ejo/cjn108. Epub 2009 Feb 4.

32. Caglar E., Kuscu O. O., Selvi Kuvvetli S., Kavaloglu Cildir S., Sandalli N., Twetman S., Short-term effect of ice-cream containing Bifidobacterium lactis Bb-12 on the number of salivary mutans streptococci and lactobacilli. Acta Odontol Scand. Jun;66(3):154-8. 2008.

33. Hedayati-Hajikand, T., Lundberg, U., Eldh, C., & Twetman, S. (2015). Effect of probiotic chewing tablets on early childhood caries—a randomized controlled trial. BMC oral health, 15(1), 112. doi:10.1186/ s12903-015-0096-5.

34. Caglar E., Sandalli N., Kuscu O.O., Durhan M.A., Pisiriciler R., Caliskan E. A., Kargul B. Viability of fibroblasts in a novel probiotic storage media. Dent Traumatol. Oct;26(5):383-7. 2010.

35. Saini D., Gadicherla P., Chandra P., Anandakrishna L., Coconut milk and probiotic milk as storage media to maintain periodontal ligament cell viability: an in vitro study. Dent Traumatol. 2017 Jun;33(3):160-164. doi: 10.1111/edt.12310. Epub 2016 Dec 12.

36. Trasande, L. et al. Infant antibiotic exposures and early-life body mass. Int. J. Obes. 37, 16–23 2013. 37. Virta, L., Auvinen, A., Helenius, H., Huovinen, P. & Kolho, K. Association of repeated exposure to antibiotics with the development of pediatric Crohn’s disease-a nationwide, register-based Finnish Case-Control Study. Am. J. Epidemiol. 175, 775–784 .2012.

38. Honda K., Littman, D. R. The microbiota in adaptive immune homeostasis and disease. Nature 535, 75–84, https://doi.org/10.1038/nature18848 .2016.

39. Sheiham A., James W. P. A new understanding of the relationship between sugars, dental caries and fluoride use: implications for limits on sugars consumption. Public Health Nutr. 2014 Oct;17(10):2176-84. doi: 10.1017/S136898001400113X. Epub 2014 Jun 3.

40. Pubmed search, March 2019. 2530 clinical trials and 26072 articles.

41. Schnadower D. et al. Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. N Engl J Med. Nov 22;379(21):2002- 2014. 2018.

42. Freedman S. B., et al. Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis. N Engl J Med. Nov 22;379(21):2015-2026. 2018.

43. Licciardi P. V., Tang ML.Vaccine adjuvant properties of probiotic bacteria. Discov. Med. 12 525–533. 2011.

44. Schnadower D., Finkelstein Y., Freedman SB;Ondansetron and probiotics in the management of pediatric acute gastroenteritis in developed countries. Curr. Opin. Gastroenterol. 31 1–6. 10. 2015.

45. Sindhu K. N., Sowmyanarayanan T. V., Paul A., Babji S., Ajjampur S. S., Priyadarshini S., et al. Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 58 1107–1115. 2014.

46. Lei, S., Ramesh, A., Twitchell, E., Wen, K., Bui, T., Weiss, M., Yuan, L. (2016). High Protective Efficacy of Probiotics and Rice Bran against Human Norovirus Infection and Diarrhea in Gnotobiotic Pigs. Frontiers in microbiology, 7, 1699. doi:10.3389/fmicb.2016.01699

47. Riedel S. (2005). Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center), 18(1), 21-5.

48. Dominy, S. S. et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors, Science advances vol. 5,1 eaau3333. 23 Jan. 2019, doi:10.1126/sciadv.aau3333.

49. Kim, H. J., Cha, G. S., Kim, H. J., Kwon, E. Y., Lee, J. Y., Choi, J., & Joo, J. Y. (2018). Porphyromonas gingivalis accelerates atherosclerosis through oxidation of high-density lipoprotein. Journal of periodontal & implant science, 48(1), 60-68. doi:10.5051/jpis.2018.48.1.60

50. Hussain M., Stover C. M., Dupont A., P. gingivalis in Periodontal Disease and Atherosclerosis–Scenes of Action for Antimicrobial Peptides and Complement. Front Immunol. Feb 10;6:45. 2015.

51. Rotavirus: vaccination. Centers for Disease Control and Prevention website. https://www.cdc.gov/rotavirus/vaccination.html . Updated August 12, 2016.

52. Preventing norovirus infection. Centers for Disease Control and Prevention website. https://www.cdc.gov/norovirus/preventing-infection.html . Updated July 15, 2016.