Written by: Hailey Motooka, Bonnie Feldman, DDS, MBA, Ellen M. Martin

Meet one of today’s pioneers of oral microbiology…

If the concept of The Force in Star Wars were applied to oral microbiology, then Dr. John Tagg would be the Obi-Wan Kenobi of this modern scientific galaxy. Instead of Legos and video games, the young John was intrigued by watching bacteria grow on petri dishes. Through his extensive breadth of knowledge in microbiology, it would be accurate to say that the Force is strong with this one.

“Even ‘til this day, I start my work day by looking at my cultures growing in my lab”

-Dr. John Tagg

Despite his passion for science at a young age, John did not engage in the traditional study of microbes until he was an undergraduate student at Melbourne University. There, he learned about bacteriocins–a form of antibiotics produced by bacteria that interfere with the growth of other closely related bacteria.

This insight into the properties and capabilities of bacteriocin-producing microbiota made him consider the possible ways microbes within our bodies could be used as a first line of tissue defense. In particular, he wanted to employ the natural defense mechanisms of bacteriocin to target harmful bacterial species such as Streptococcus pyogenes (Tagg 2009).

The Road to BLIS

To find an antagonist of S. pyogenes that contained bacteriocin-like inhibitory substance (BLIS), Dr. Tagg conducted a 6-year study of 100 New Zealand school children. Throughout the course of the study he regularly documented the children’s oral microbial composition, with particular attention to the presence, absence, or acquisition of S. pyogenes (2).

A breakthrough came in his study when Dr. Tagg and his team isolated a strain of S. salivarius (K12) from a child with remarkable throat health. Afterwards, follow-up studies found that S. salivarius BLIS was active against S. pyogenes by producing salivaricin A and B. (Salivaricin is a lantibiotic inhibitory to most S. pyogenes, aka Salivaricin kills or stops reproduction of S. pyogenes.) The effects of S. salivarius K12 were then tested against other pathogens and found to inhibit the following additional species:

Inhibition of key pathogens by K12

Additionally, a number of clinical studies have also been conducted with Streptococcus salivarius K12 to assess the efficacy of daily delivery of the probiotic and its ability to promote good oral health. The clinical trials found that the Streptococcus salivarius K12 probiotic can reduce:

• Oral Infections

Oral streptococcal BLIS: Heterogeneity of the effector molecules and potential role in the prevention of streptococcal infections

Production of the Lantibiotic Salivaricin A and Its Variants by Oral Streptococci and Use of a Specific Induction Assay To Detect Their Presence in Human Saliva

• Halitosis (bad breath)

A preliminary study of the effect of probiotic Streptococcussalivarius K12 on oral malodour parameters

Diversity of Bacterial Populations on the Tongue Dorsa of Patients with Halitosis and Healthy Patients

• Upper Respiratory Tract Infections

Positive clinical outcomes derived from using Streptococcus salivarius K12 to prevent streptococcal pharyngotonsillitis in children: A pilot investigation

Preliminary pediatric clinical evaluation of the oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes and recurrent acute otitis media

Along with the discovery of strain S. salivarius K12, they isolated another strain of S. salivarius M18 that was found to have inhibitory effects on bacterial species such as S. mutans and S. sobrinus (collectively referred to as mutans streptococci), which are associated with dental caries. Along with the potential to reduce risk of dental caries, S. salivarius M18 has also demonstrated additional benefits in helping to limit the growth of common bacterial pathogens in the upper respiratory tract. S. salivarius M18 was tested against a variety of oral pathogens and was found to be most effective in inhibiting the following:

Inhibition of key pathogens by M18

Clinical trials have also demonstrated that BLIS M18 is beneficial against:

• Dental Caries

Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study

• Periodontal Diseases and Gingivitis

Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probiotics

• Colonisation

Persistence of the Oral Probiotic Streptococcus salivarius M18 Is Dose Dependent and Megaplasmid Transfer Can Augment Their Bacteriocin Production and Adhesion Characteristics

What’s awesome about the use of S. salivarius strains as a biological weapon to target oral pathogens, is that BLIS-producing S. salivarius are already indigenous salivary microbes. They aren’t foreign to our bodies, and the addition of these beneficial strains should only help maintain homeostasis within the mouth without negatively impacting the normal oral microbiota. Previously, there has been a cause for concern about high-level oral dosing with S. salivarius K12 and its possible link to increasing of IFN-𝛾 –a common pro-inflammatory cytokine. However, a closer analysis of the gene pathways involved indicated that K12 helps maintain homeostasis between human and bacterial cells and may actually reduce proinflammatory cytokine responses.

Ways to make the bacteria stick

It was determined that the probiotic is most effective and more persistent with higher doses. Due to the fact that not all BLIS-producing S. salivarius are able to colonize the host, the persistence of the probiotic is dose dependent and advises users to take the probiotic at least twice a day. BLIS Technologies offers the probiotics in a variety of forms including lozenges, gum, and powder (which they have added to make a probiotic ice cream). Although all options are available and the probiotic ice cream delicious, the lozenges are recommended as the most effective method for microbial colonization. This raises some skepticism about other oral probiotic companies which offer their product in the form of a drink. In order for proper microbial adhesion they must be exposed to oral surfaces for an extended period of time, which may not be possible if one is simply gulping the liquid right down.

BLIS Technologies’ various deliverables are constantly updated by current research to ensure maximal possible colonization of K12 and M18. Due to their novel product designs, they have been able to tackle the obstacle of ensuring that the bacteria do indeed “stick”. Although they have a fantastic product, they haven’t had as much success within the consumer market, (the US in particular) where the concept of probiotics is still somewhat foreign. But after all of this novel and fascinating research and results, do you want try their K12 and M18 probiotic?

The man behind the BLIS design

If Dr. Tagg is the Obi-Wan Kenobi of the microbiology galaxy, then inevitably Dr. John Hale is Luke Skywalker. Dr. Hale has studied under Dr. Tagg since 2011 and has since carried out his own post-doctoral research at the University of British Columbia, Canada, and Monash University School of Pharmacy in Melbourne Australia. Dr. Hale has been instrumental in the creation of BLIS Technologies by taking the years of science and research (headed by Dr. Tagg) and translating it into useful products and services for consumers.

“There is a lot of awareness of the gut microbiome, with some growing understanding of the skin and vaginal microbiome, but  oral health elements are missing.I love traveling the world, educating scientists and practitioners about the value of our oral probiotics to improve oral health”

                                  -Dr. John Hale

There is only a single dental school within New Zealand where Dr. Tagg taught, rather than the hundreds? of dental schools within the United States. This means all New Zealand dental students are aware of the importance of the oral microbiome and its effects on systemic disease.  Because of this, dentists in New Zealand frequently recommend their patients to use probiotics. The BLIS ThroatGuard™ is also one of the best selling products in the cold and cough category within pharmacies in New Zealand.

“Throughout my teaching career I communicated with many of my students using a reciprocal nose-tapping gesture sometimes accompanied by the utterance

‘May the BLIS be with you’.

This was a way of signifying membership of the so-called BLIS Secret Society – the guiding principle of which was a belief in the philosophy that prevention is better than cure. Many former students (and also the current Vice Chancellor of the University of Otago) still regularly greet me with a nose tap.”

-Dr. John Tagg

Finally, the collaboration of Dr. John Tagg and Dr. John Hale has been instrumental in the creation of the world’s FIRST bacterial replacement probiotic. The probiotic field is rapidly expanding as scientists and the general public are becoming more aware of the role of bacteria within our bodies, and how maintaining balance within these oral microbial populations have numerous potential health benefits. The probiotic movement is rapidly gaining speed, and it’s important to know the two oral microbiome jedis that are leading the way.

References

1. Tagg, John Robert. “Streptococcal Bacteriocin-Like Inhibitory Substances: Some Personal Insights into the Bacteriocin-Like Activities Produced by Streptococci Good and Bad.” Probiotics and Antimicrobial Proteins, vol. 1, no. 1, 2009, pp. 60–66., doi:10.1007/s12602-008-9002-7.
2. Wescombe, Philip A, et al. “Developing Oral Probiotics FromStreptococcus Salivarius.” Future Microbiology, vol. 7, no. 12, 2012, pp. 1355–1371., doi:10.2217/fmb.12.113.
3. Tagg, J., et al. “Oral Streptococcal BLIS: Heterogeneity of the Effector Molecules and Potential Role in the Prevention of Streptococcal Infections.” International Congress Series, vol. 1289, 2006, pp. 347–350., doi:10.1016/j.ics.2005.11.016.
4. Wescombe, P. A., et al. “Production of the Lantibiotic Salivaricin A and Its Variants by Oral Streptococci and Use of a Specific Induction Assay To Detect Their Presence in Human Saliva.” Applied and Environmental Microbiology, vol. 72, no. 2, Jan. 2006, pp. 1459–1466., doi:10.1128/aem.72.2.1459-1466.2006.
5. Burton, J.p., et al. “A Preliminary Study of the Effect of Probiotic Streptococcus Salivarius K12 on Oral Malodour Parameters.” Journal of Applied Microbiology, vol. 100, no. 4, 2006, pp. 754–764., doi:10.1111/j.1365-2672.2006.02837.x.
6. Kazor, C. E., et al. “Diversity of Bacterial Populations on the Tongue Dorsa of Patients with Halitosis and Healthy Patients.” Journal of Clinical Microbiology, vol. 41, no. 2, Jan. 2003, pp. 558–563., doi:10.1128/jcm.41.2.558-563.2003.
7. Pierro, Francesco Di, et al. “Positive Clinical Outcomes Derived from Using Streptococcus Salivarius K12 to Prevent Streptococcal Pharyngotonsillitis in Children: a Pilot Investigation.” Drug, Healthcare and Patient Safety, Volume 8, 2016, pp. 77–81., doi:10.2147/dhps.s117214.
8. Pierro, Francesco Di, et al. “Preliminary Pediatric Clinical Evaluation of the Oral Probiotic Streptococcus Salivarius K12 in Preventing Recurrent Pharyngitis and/or Tonsillitis Caused by Streptococcus Pyogenes and Recurrent Acute Otitis Media.” International Journal of General Medicine, 2012, p. 991., doi:10.2147/ijgm.s38859.
9. Pierro, Francesco Di, et al. “Cariogram Outcome after 90 Days of Oral Treatment with Streptococcus Salivarius M18 in Children at High Risk for Dental Caries: Results of a Randomized, Controlled Study.” Clinical, Cosmetic and Investigational Dentistry, 2015, p. 107., doi:10.2147/ccide.s93066.
10. Wescombe, Philip A, et al. “Streptococcal Bacteriocins and the Case for Streptococcus Salivariusas Model Oral Probiotics.” Future Microbiology, vol. 4, no. 7, 2009, pp. 819–835., doi:10.2217/fmb.09.61.
11. Burton, Jeremy P., et al. “Persistence of the Oral Probiotic Streptococcus Salivarius M18 Is Dose Dependent and Megaplasmid Transfer Can Augment Their Bacteriocin Production and Adhesion Characteristics.” PLoS ONE, vol. 8, no. 6, 2013, doi:10.1371/journal.pone.0065991.