Transplantation of a Health-associated Oral Microbiome in the treatment of periodontitis

• Applicant: Professor Dr. Thomas Beikler
• Subject Area: Dentistry, Oral Surgery
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 313546205

Background: The cure of periodontitis has been an elusive goal. Although established periodontal therapies may improve periodontal health, they fall short of arresting progressive attachment loss and often do not prevent tooth loss in subjects with severe forms of periodontitis. Evidence strongly suggests an oral dysbiosis in subjects with periodontitis. In one third of the approximately 600 bacterial species that have been identified in subgingival biofilms, abundance differences have been found between healthy and diseased periodontal sites. Furthermore, in subjects with periodontitis a shift towards a disease associated microbiota has been found in healthy periodontal sites, buccal mucosae, tongue, and saliva. Objectives: The objective of the proposed project is to assess whether oral microbiota transplantation can improve periodontitis associated clinical parameters following full mouth debridement. In addition, the dynamics of the oral microbial communities, host response, and adverse events following oral microbiota transplantation will be assessed. Methods: Fourteen beagle dogs with naturally occurring periodontitis and one periodontally healthy beagle dog will be enrolled into the study. All dogs will receive scaling and root planing to establish periodontal health at baseline. Two weeks later, the beagle dogs will be randomly assigned to receive either full mouth debridement followed by oral microbiome transplantation from a healthy donor beagle dog (Test; n = 7) or full mouth debridement alone (Control; n = 7). Full mouth debridement in supra and subgingival sites and on oral mucosae will be performed using a low abrasive glycine powder air polishing technique with adjunctive sodium hypochlorite irrigation. Following inactivation of sodium hypochlorite with buffered sodium ascorbate, periodontal pockets and mucosal surfaces in Test dogs will be inoculated with an oral microbiome transplant harvested from the periodontally healthy dog. Clinical measurements, oral microbial samples, and gingival crevicular samples will be taken at Baseline, Week 2, Week 4 and Week 14. Probing depths at Week 14 will be used as primary outcome variable. The dynamics of oral microbial communities will be assessed by Illumina next generation DNA sequencing and qrt PCR. Pro inflammatory and Th1 cytokines in gingival crevicular fluid will be analyzed using a multiplex immunoassay. Safety will be evaluated by monitoring and recording adverse events and by histomorphometric analysis of gingival biopsies taken at Week 14. Innovation: The study will demonstrate the feasibility of an innovative approach in the treatment of periodontitis that may further result in the development of new strategies in the prevention and treatment of other oral biofilm-associated diseases.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Astrid Klocke; Dr. Ulrike Peters