Abstract: SA-PO672
Uremic Periodontitis: Bacterial Dysbiosis and Immune Dysfunction
Session Information
- Bone and Mineral Metabolism: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Randall, David, Queen Mary University of London, London, United Kingdom
- Alsam, Asil, Kings College London, London, United Kingdom
- Kieswich, Julius Edward, Queen Mary University of London, London, United Kingdom
- Joseph, Susan, Kings College London, London, United Kingdom
- Mccafferty, Kieran, Queen Mary University of London, London, United Kingdom
- Curtis, Michael A., Kings College London, London, United Kingdom
- Yaqoob, Muhammad M., Queen Mary University of London, London, United Kingdom
Background
Patients with CKD have a high incidence of periodontitis, which acts as a marker for increased mortality in these individuals. We sought to establish whether this represents a causal association, and to understand the mechanisms responsible.
Methods
Two models of CKD were used in wild-type Wistar rats: feeding with 0.75% adenine and subtotal nephrectomy. Of the uremic animals, half were housed with other uremics whilst half were housed with controls. The oral microbiome was assessed using next-generation sequencing and culture-based methods. Periodontal bone loss was measured as the distance between the cemento-enamel junction and the alveolar bone ridge, supplemented by immunohistochemistry, micro-CT imaging and scanning electron microscopy.
Results
In both models of CKD, uremic rats displayed significantly more periodontal bone loss than controls (alveolar bone level > 0.1mm lower in uremics, p<0.0001). These animals displayed substantial oral dysbiosis compared to controls, including a reduction in cultured bacterial counts (log 5.95 vs log 6.21, p=0.05), increased alpha diversity (Inv Simpson index 10.3 vs 6.46, p=0.03), a decline in health-associated phylum Firmicutes (55.2% vs 66%, p=0.05) and genus Streptococcus (29.8% vs 45.8%, p=0.004), and an increase in disease-associated Gammaproteobacteria (29.6% vs 19.4%, p=0.038). Histology and imaging confirmed bone disease associated with IL-17 driven inflammation. Significantly, uremic rats housed with healthy controls demonstrated milder bone loss than those housed with other uremics (p=0.037).
Conclusion
This work proves for the first time that periodontitis can be caused by uremia. A key role for bacterial dysbiosis is suggested from the fact that periodontal disease was partially reversed in uremic animals housed with controls. We propose that oral bacterial dysbiosis induces Th17-driven inflammatory periodontal bone loss.