Socransky, S.S. and Haffajee, A.D. The bacterial etiology of destructive periodontal disease: current concepts. J. Periodontal. 63 (4 Suppl): 322-331, 1992.

Following conventional periodontal therapy, studies have shown that the long-term success of the therapy correlated with whether or not streptococcus veridans, including S. oralis and S. uberis, recolonized the periodontal sites.

Hillman, J.D. and Shivers, M. Interactions 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, 1988.

Streptococcus oralis and Streptococcus uberis were shown to efficiently inhibit the growth of periodontal pathogens because of their ability to produce significant amounts of hydrogen peroxide, an antagonistic agent to the pathogens.

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

The presence of Streptococcus oralis and Streptococcus uberis was shown to reduce the risk of finding various periodontal pathogens in dental plaque. The relationship was shown to be dose-dependent by demonstrating that the risk of finding a particular pathogen decreased as the proportion of the beneficial stains increased.

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

Plaque from healthy subjects and from healthy sites in patients with periodontal (gum) disease was shown to contain bacteria that inhibit the growth of a certain bacteria known to cause periodontal disease. In contrast, plaque from diseased sites in subjects with periodontal disease was shown to lack these beneficial bacteria. The beneficial bacteria were identified as Streptococcus oralis and Streptococcus uberis.

Johnson, C.P., Gross, S.M. and Hillman, J.D.** 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, 1980.

JH145, a completely natural strain of Streptococcus rattus -which until recently was considered to be one of several subspecies of Streptococcus mutans - was shown to make virtually no lactic acid. Since the strain does not make lactic acid, it was demonstrated to be essentially incapable of causing dental caries in a rat model.

Zahradnik, R.T., McDonell, E., Hillman, C.H. and Hillman, J.D. Dental whitening effect produced in vitro by Streptococcus oralis. (Manuscript submitted for publication).

In a controlled laboratory study, Streptococcus oralis strain KJ3sm™, a component of Probiora3, demonstrated an ability to effectively whiten stained dental ceramic disks. The basis for the observed whitening effect was shown to be due to hydrogen peroxide production by KJ3sm™.

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. (Manuscript submitted for publication).

The probiotic mouthwash, containing three strains of naturally occurring oral bacteria, was determined to be well tolerated and safe in humans and was able to substantially reduce the levels of dental and periodontal pathogens in the mouths of the study’s human volunteers.

Hillman, J.D., McDonell, E., Cramm, T., Hillman, C.H. and Zahradnik, R.T. A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries. (Manuscript submitted for publication).

The results of this animal model study indicated that daily application of the S. rattus strain, JH145, successfully competed with an established, decay-causing strain of Streptococcus mutans for the habitat on the tooth surface, resulting in a significant reduction of their numbers in the mouth.

Pre-publication Manuscripts: Hillman, J.D., McDonell, E., Hillman, C.H. and Zahradnik, R.T. Chronic animal toxicity study of ProBiora3™, a probiotic mouthwash. (Manuscript submitted for publication).

The ProBiora3 product was determined to be safe for human use based on the results of long-term exposure of rats to a mixture of the three strains in the ProBiora3. Furthermore, all three bacterial strains were susceptible to commonly used antibiotics, an important property for any probiotic strain intended for human use.

Twetman, S. and Stecksen-Blicks, C. Probiotics and oral health effects in children. Internat. J. Pediatric Dent. 18: 3-10, 2008.

Bacteriotherapy in the form of probiotic bacteria with an inhibitory effect on oral pathogens is a promising concept, especially in childhood, but this may not necessarily lead to improved oral health. For example, the well documented observation that Lactobacillus species promote the progression of dental cavities requires that the pathogenic potential of these strains be carefully considered. ** Dr. Jeffrey D. Hillman as the inventor of this ProBiora3 technology. He is the Chief Scientific Officer at Oragenics.

Meurman, J.H. and Stamatova, I. Probiotics: contributions to oral health. Oral Diseases 13: 443-451, 2007.

An essential requirement for a microorganism to be an “oral probiotic” is to be a natural resident of the mouth and thus to have an ability to adhere to and colonize surfaces in the oral cavity. Microorganisms generally considered as probiotics may not have the oral cavity as their inherent habitat and, subsequently, their possibility to confer benefit on oral health is then questionable.

General Published Probiotics Review Articles: Walker, R. and Buckley, M. (eds.). Probiotic microbes: the scientific basis. In A Report of the American Academy in Microbiology: American Society for Microbiology, Washington D.C., 2006

New probiotic formulations should, first and foremost, be safe to use. Validating the safety of prospective probiotics must include laboratory and animal testing to ensure the strain is not pathogenic. Probiotic organisms must also be free of plasmid-encoded antibiotic resistance genes which could be potentially passed to pathogenic organisms in the product user.