Repeated Oral Inoculation With Porphyromonas Gingivalis or Treponema Denticola Induces Alzheimer’s Disease Like Pathologies in a Mouse Model.

Objectives: Periodontitis is a chronic inflammatory disease caused by dysbiosis in subgingival bacterial biofilms that is characterised by a proliferation of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Periodontitis is a modifiable risk factor for Alzheimer’s disease (AD) pathogenesis, with components of both these bacteria identified in post-mortem AD brains. The objective of this study was to determine the effects of oral inoculation of these bacteria on the brain using a murine model of disease.
Methods: T. denticola and P. gingivalis were grown in continuous culture, harvested and administered orally to mice 3-times per week for 12 weeks. C57/Bl6 mice were killed at 13 weeks whereupon jaws were examined for alveolar bone loss and brains collected for histological examination and transmission electron microscopy imaging to determine the induction of AD like pathologies and for detection of T. denticola and P. gingivalis whole cells and components.
Results: Repeated oral inoculation of mice with P. gingivalis or T. denticola resulted in brain infiltration of bacterial products, increased inflammation and induction of AD-like biomarkers, but without whole bacterial cells infecting the brains. Bacterial components were detected in the hippocampus, but whole bacterial cells were not identified using transmission electron microscopy. There was a trend of increasing AD biomarker Amyloid beta42 in the hippocampus of all mice inoculated with bacteria compared with control mice. Oral inoculation with P. gingivalis but not T. denticola resulted in significant alveolar bone loss compared with sham inoculated mice.
Conclusions: In this study we have demonstrated that oral inoculation with either P. gingivalis or T. denticola results in penetration of the mouse brain by bacterial products, but not whole cells, that results in the induction of AD biomarkers. It is likely that the bacterial proteins, particularly P. gingivalis RgpA, are translocated into the mouse brain on outer membrane vesicles.