Technical Background.  Dr. Hillman identified three natural strains of bacteria that, when combined into a single mixture, can be employed as a probiotic product for the maintenance of dental and periodontal (gum) health.  Laboratory and animal studies have demonstrated the ability of these specific organisms to maintain a healthy oral environment for the beneficial microflora which assists in retaining healthy gums and teeth.

Pre-Clinical Studies.  Research by Dr. Hillman and his collaborators has demonstrated that certain types of natural bacteria normally present in dental plaque can prevent the growth of bacteria that are widely believed to be responsible for periodontal disease.  The beneficial bacteria are called Streptococcus oralis and Streptococcus uberis.  These bacteria have been shown to help provide a balance between the amount of healthy oral microflora and the disease-causing bacteria both in the laboratory and in animal models of infection.  Analysis of data from a number of laboratories indicated that the presence of S. oralis and S. uberis provided a good indication of the health of the gums.  When these bacteria are present in the sites and around the gums, the sites are much more likely to be healthy.  In order to maintain a healthy balance of bacteria in and around the gums, Oragenics’ commercially available oral healthcare product contains two specific, natural probiotic strains: S. oralis strain KJ3 and S. uberis strain KJ2.

            Most human tooth decay has been shown to be caused by Streptococcus mutans that live on nearly everyone’s tooth surfaces and converts sugar in their diet to lactic acid.  The lactic acid erodes the mineral in enamel and dentin, weakening the tooth and ultimately resulting in decay.  Dr. Hillman’s research has led to the discovery of a particular strain of Streptococcus rattus (JH145) that is naturally deficient in its ability to produce lactic acid and cause tooth decay.  Because Streptococcus rattus is very closely related to S. mutans, Dr. Hillman hypothesized that daily treatment with this beneficial strain could significantly reduce the numbers of S. mutans by competing for nutrients and attachment sites on the tooth surface.  This hypothesis has been tested in laboratory animals and was confirmed.  Therefore, Oragenics’ probiotic product contains a mixture of three natural bacteria that includes the lactic acid-deficient S. rattus strain JH145 for the maintenance of dental health, in addition to the two strains identified above for the maintenance of periodontal health, S. oralis KJ3 and S. uberis KJ2.

Regulatory Status.  Oragenics completed a human study in November 2006, to support product claims its ProBiora3 food ingredient product.  Based on review and analysis of the clinical data, the trial met the Company’s primary clinical endpoint by demonstrating a substantial effect of ProBiora3 in reducing the levels of specific disease-causing bacteria in the mouths of young, physically and orally healthy adult subjects.  Reductions in Streptococcus mutans, a bacterium that attacks teeth, and two bacterial strains associated with gum disease, P. gingivalis and Campylobacter rectus, were observed with subjects after only two to three weeks of product use.  C. rectus, for example, was reduced, on average, to less than 1% of its pretreatment levels in plaque collected from below the gum line.  This trial also demonstrated that ProBiora3 was safe and well tolerated during the course of product use.

            During the fourth quarter of 2008, the Company obtained self-affirmed GRAS (Generally Recognized as Safe) status for its ProBiora3 food ingredient in the US, and launched launched the ProBiora3 food ingredient for sale to qualified formulators/manufacturers, and also launched a finished product, EvoraPlus™, for direct sales and subsequent distribution through major retail outlets to the consumer oral healthcare market.

ProBiotics: Scientific Articles (Click links below to view articles if available)

Hillman, J.D. 1978. Lactate dehydrogenase mutants of Streptococcus mutans: isolation and preliminary characterization. Infect Immun 21: 206-212.

Johnson, C.P., Gross, S.M. and Hillman, J.D. 1980. Cariogenic potential in vitro in man and in vivo in the rat of lactate dehydrogenase mutants of Streptococcus mutans. Arch Oral Biol 25: 707-713.

Socransky, S.S., Tanner, A.C.R., Haffajee, A.D., Hillman, J.D., and Goodson, J.M. 1982. Present status of studies on the microbial etiology of periodontal disease. In: Host-Bacterial Interactions in Periodontal Disease (R.J. Genco and P. Mergenhagen, eds.), A.S.M. Publications, Washington D.C., pp. 1-12.

Hillman, J.D. and Socransky, S.S. 1982.  Bacterial interference in the oral ecology of Actinobacillus actinomycetemcomitans and its relationship to human periodontosis. Arch Oral Biol 27: 75-77.

Hillman, J.D., Socransky, S.S., and Shivers, M. 1985. The relationships between streptococcal species and periodontopathic bacteria in human dental plaque. Arch Oral Biol 30: 791-795.

Hillman, J.D., Yaphe, B.I., and Johnson, K.P. 1985. Colonization of the human oral cavity by a strain of Streptococcus mutans. J Dent Res 64: 1272-1274.

Socransky, S.S., Haffajee, A.D., Dzink, J.L., and Hillman, J.D. 1988. Associations between microbial species in subgingival plaque samples. Oral Microbiol Immunol 3: 1-7.

Hillman, J.D. and Shivers, M. 1988. Interaction between wild-type, mutant and revertant forms of the bacterium Streptococcus sanguis and the bacterium Actinobacillus actinomycetemcomitans in vitro and in the gnotobiotic rat. Arch Oral Biol 33: 395-401.

Hillman, J.D., McDonell, E., Hillman, C.H., and Zahradnik, R.T.  Safety assessment of ProBiora3™, a probiotic mouthwash: subchronic toxicity study in rats.
View Abstract

Zahradnik, R.T., Magnusson, I., Walker, C., McDonell, E., Hillman, C.H., and Hillman, J.D.  Preliminary assessment of safety and effectiveness in humans of ProBiora3™, a probiotic mouthwash. J Applied Micro. In Press.