You might try Eastern Eoropean and the Russian literature as it is my understanding they have been using phage therapies for >70 years.

In chronic periodontitis, tissue damage is caused by the immune host response rather than direct action of biofilms microorganisms, which generally are not particularly virulent. Control of inflammation after periodontal clinical therapy can prevent recurrences better than an antimicrobial approach. Juvenile periodontitis and necrotizing periodontitis would be an exception and they relate to aggressive microorganisms

It is true, dr. Arreaza, however, to my understanding, the abnormal immune response is mainatained due to the persistence of the germs in the tissues, especially inside the cells.

Yes, the "normal" immune response against the persistence of the germs in the tissues lead with time to tissue destruction observed in periodontitis but the use of bacteriophages may trigger further inflammation and therefore greater destruction

Thank you. I was thinking of genetically engineered bacteriophages as vectors for useful genes - indeed, a certain margin of safety is required.

For the sake of excessive precision, I daresay that the periodontitis causing germs are capable of influencing/modifying the physiological immune response (production of proteases that destroy antibodies, toxins that kill the polimorphonucleates and linphocytes, induction of their apoptosis, represion of sinthesys of IL8), in order to survive it, with the effect that it becomes oriented mainly towards tissue destruction as last resort in stopping the diffusion of this infection.

Only clinical application of genetically modified phages in periodontal therapy that i an think of is in cases of aggressive periodontitis... In aggressive periodontitis aggregatibacters are known to penetrate into the tissues and cause extensive damage.. By use of targetted bacteriophages one can look for reduction in disease progression...

Our group, working on subgingival biofilms was discussing the issue of using phages against putative periodontal pathogenes. We were collaborating with the Robert-Koch Institute in Berlin with microbiologists there and we had a contact in fact to one surgeon from Russia, who is running a company in Germany selling phages. However, all the above mentioned aspects are true for our field of periodontitis and there are even much more to tell. Talking about A.a. one should take into account that only certain serotypes (B) are virulent in terms of leucotoxin secretion, in others strains being completely avirulent are well known. Additionally, even throughout russian specialists noone has any idea, were phages against gram negatives are to isolate from. Therefore, the therapy of periodontitis remains a complex issue targeting at resolution of the inflammatory process and reducing the probing depth.

Very interesting insights, thank you. It is also said that we have not identified all bacterial species involved in oral pathologies (and subsequently, neither their interactions in this ecosystem).

Thank you all for your answers. I think we should further research, if phages are able to "disturb" the biofilm and if they can be useful in the treatment of periodontitis and maybe also caries.

Anaerobic bacteria readily develop drug resistance to antibiotics, but not to the calcium materials that we have successfully utilized to resolve perio disease over the last 50 years. These calcium materials are safe, have rapid onset, and long- lasting consilience, i.e. they integrate with the rest of the body of knowledge we have of the clinical phenomena and facts.

Thank you, Dr. Manhart - can you provide further information about those Ca-Materials you are using for periodontal disease?

Dr. Schueker, The calcium materials are timed-release liquids, pastes, particles and applications we designed for every dental field, every inch of skin, and some with collateral benefits in internal medicine. Others have zinc, or are less intense for homecare maintenance. They virtually "dictate" the oral biofilm. Your research interest is refreshing. We've done a some lab and & 50 yrs. of clinical studies & want to do more. Yes, perio disease is a complex condition that we have resolved in the most hopeless cases using calcium materials and there is no reason we cannot understand it better, control it, and eliminate it.

Dear Ina! We have been working with bacteriophages for about 5 years. In Russia there is a company with the largest registered collection of bacteriophages, they developed the first and exclusive gel based with bacteriophages "Phagodent". It includes 56 species of bacteriophages against 19 periodontopathogenes. Throughout this time, we have received excellent results. Especially it’s worth noting their high effectiveness in patients with antibiotic resistance, with allergy to antimicrobials medicines, in pregnant and lactating women. If you are interested in the details, you can write to me on my personal mail: [email protected]. I will be pleased to answer your questions. Regards, Karina.