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Diabetes Impact on Periodontitis Pathogenesis
- 1. Diabetes Impact on Periodontitis By: Deyana Nasri Scannapieco Lab, Department of Oral Biology
- 2. • infection that damages the gingiva and alveolar bone What is periodontitis? 1. Van Dyke et al., 2014 2. CDC, 2012 Lee, 2017 • 47.2% of the population above 30 has some form of periodontitis • multistage disease
- 3. 2 key components: Pathogenesis of Periodontitis Dominy et al., 2019 Figuerdo et al., 2019 Microbial shift/Dysbiosis Host Inflammatory pathways
- 4. ● essentially a “microbial shift”/dysbiosis occurs changing a healthy oral microbiome to be pathogenic ● changes symbiotic host-microbe relationship to pathogenic Pathogenesis - Dysbiosis Dominy et al., 2019 1. Teles et al., 2013 2. Zhang et al., 2019 3. Nath & Raveendran, 2013 ● The oral microbiome houses ~700 types of microbes ● symbiotic microbe-host relationship ● dysbiosis leads to a pathogenic relationship ● reduction of gram positive aerobes and over abundance of gram negative anaerobes ● new microbial complexes → orange complex, red complex Orange complex bacteria: Prevotella intermedia Prevotella nigrescens Prevotella micros Fusobacterium Campylobacter gracilis Campylobacter rectus Leptotrichia bucallis Campylobacter showae Campylobacter ochracea Red Complex Bacteria: Porphyromonas gingivalis Treponema denticola Tannerella forsythia Eubacterium nodatum Eubacterium saburreum Aggregatibacter actinomycetemcomitans Prevotella melaninogenica Prevotella micra filifactor alocis
- 5. Pathogenesis - Inflammatory Response Munoz-Carillo et al., 2018 Initial lesion - polymorphonuclear leukocytes infiltrate the gingival sulcus, increase in fibrin Early lesion - accumulation of T cells and cytokine release Established lesion - dense infiltration of T cells and B cells, RANKL production Advanced lesion - further infiltration of B cells and T cells, B cell autoantibodies breakdown gingival tissue Figuerdo et al., 2019
- 6. • Cardiovascular disease • Alzheimer's disease • Osteoporosis • Rheumatoid Arthritis • Parkinson's Disease • Lung Diseases Comorbidities Holmstrup et al., 2017 Jimenez et al., 2012 • Diabetes
- 7. What we Know So Far... Presence of Diabetes Increased incidence of periodontitis Exacerbates progression of periodontitis WHY?
- 8. Question: What are the mechanisms and factors that contribute to this increased incidence and exacerbation of periodontitis in diabetics?
- 9. Overlap Between Periodontitis and Diabetes - dysbiosis of the oral microbiome increase in red and orange complex bacteria Change in oral microbiome Increase in inflammation Increased incidence of: - nerve damage - heart disease - Kidney failure Increased insulin resistance chronic inflammatory- immune response - inflammatory response resulting in an increase in cytokines, T cells, RANKL etc high glucose levels in saliva which changes nutrient sources for bacteria Diabetes Periodontitis
- 10. Hypothesis: Diabetes increases the incidence of periodontitis by fostering an oral microbiome that promotes periodontitis pathogenesis and exacerbates periodontitis by increasing the stimulation of inflammatory pathways
- 11. Methods • Worked with associate librarian at UB’s dental school • The search resulted in 276 articles • narrowed it down to 75 • Used only studies using animal models and gene sequencing
- 12. Is it the oral microbiome? Hypothesis: Diabetes increases the incidence of periodontitis by fostering an oral microbiome that promotes periodontitis pathogenesis and exacerbates periodontitis by increasing the stimulation of inflammatory pathways
- 13. • papers compared: healthy oral microbiomes to diabetic oral microbiomes • 16S rRNA sequencing of gingival epithelium samples Findings Anahatar et al., 2016 Orange complex bacteria: Prevotella intermedia Prevotella nigrescens Prevotella micros Fusobacterium Campylobacter gracilis Campylobacter rectus Leptotrichia bucallis Campylobacter showae Campylobacter ochracea Red Complex Bacteria: Porphyromonas gingivalis Treponema denticola Tannerella forsythia Eubacterium nodatum Eubacterium saburreum Aggregatibacter actinomycetemcomitans Prevotella melaninogenica Prevotella micra filifactor alocis
- 14. ● Fusobacterium ● Prevotella spp. Findings - Diabetic Oral Microbiome ● Solobacterium mooreii ● Haemophilus influenzae ● Neisseria elongata ● Filifactor alocis ● Tannerella forsythia ● Prevotella spp. ● Actinobacteria ● Bacteroidetes ● Prevotella spp. ● Rothia dentocariosa ● Veillonella Parvula ● Anaerolineae ● Leptotrichia 1. Mohanty et al., 2019 2. Denati et al., 2016 3. Tempro & Slots, 1986 4. Deng et al., 2017 5. Guthmiller & Novak., 2002 6. Yost et al., 2015 7. Farina et al., 2019 8. Matsha et al., 2020 9. Xiao et al., 2017 10. Xiayou et al., 2020 11. Zhou et al., 2015
- 15. 1) Diabetes fosters an oral microbiome that has an increased abundance of periodontopathogenic bacteria in comparison to healthy individuals 2) Diabetics display less microbial diversity in the oral microbiome 3) Those who have poorly controlled diabetes have a more pathogenic oral microbiome than those with well controlled diabetes Findings: 1. Yost et al., 2015 2. Farina et al., 2019 3. Matsha et al., 2020 4. Xiao et al., 2017 5. Xiayou et al., 2020 6. Zhou et al., 2015
- 16. Presence of Periodontitis Increased incidence of periodontitis Exacerbates progression of periodontitis WHY? Oral Microbiome increased abundance of periodontopathogenic + greater bone loss
- 17. But what about the inflammatory response? ● Oral microbiome ● Inflammatory response
- 18. Hypothesis: Diabetes increases the incidence of periodontitis by fostering an oral microbiome that promotes periodontitis pathogenesis and exacerbates periodontitis by increasing the stimulation of inflammatory pathways
- 19. Pathogenesis - Inflammatory Response Munoz-Carillo et al., 2018 Initial lesion - polymorphonuclear leukocytes infiltrate the gingival sulcus, increase in fibrin Early lesion - accumulation of T cells and cytokine release Established lesion - dense infiltration of T cells and B cells, RANKL production Advanced lesion - further infiltration of B cells and T cells, B cell autoantibodies breakdown gingival tissue Figuerdo et al., 2019
- 20. Pathogenesis - Inflammatory Response Munoz-Carillo et al., 2018 Initial lesion - polymorphonuclear leukocytes infiltrate the gingival sulcus, increase in fibrin Early lesion - accumulation of T cells and cytokine release- IL1A, IL6,TNF-a Established lesion - dense infiltration of T cells and B cells, Advanced lesion - further infiltration of B cells and T cells, B cell autobodies breakdown gingival tissue Figuerdo et al., 2019
- 21. • 4 groups Group 1: Non-diabetic PBS injection Findings - AGE deposition in Periodontitis and Diabetes Group 2: Non-diabetic P. gingivalis injection Group 3 Diabetic PBS injection Group 4: Diabetic P. gingivalis injection ● Animal model study looked at AGE accumulation in the gingival epithelium. ● wanted to see how the presence of periodontitis, diabetes, periodontitis and diabetes impacted AGEs Lalla et al., 2000
- 22. • Used immunohistochemistry to determine the presence of AGE in gingival epithelium • Found an increase in AGE to be a unique feature of diabetic environment Findings - AGE deposition Lalla et al., 2000 Non-diabetic PBS injection Diabetic PBS injection Non-diabetic P. gingivalis Diabetic P. gingivalis main takeaway: Diabetic mice had more AGEs in gingival epithelium regardless of periodontitis presence
- 23. Findings - RAGE Lalla et al., 2000 Non diabetic PBS injection Non-diabetic P.gingivalis Diabetic P.BS Diabetic mice P. gingivalis
- 24. Differences in Bone Loss Lalla et al., 2000 Zhao et al., 2015
- 25. In-vitro study of mouse osteocyte like cells impacted by AGE2 and P-LPS 4 groups: Findings - Osteocyte Cells and AGE accumulation and P- LPS sakamoto et al., 2019
- 26. Findings - AGEs and P-LPS sakamoto et al., 2019
- 27. Findings - Blocking RAGE Lalla 2000
- 28. Presence of Diabetes Increased incidence of periodontitis Exacerbates progression of periodontitis WHY? Oral Microbiome Inflammatory response greater abudnance of periodontopathogenic bacteria + greater bone loss - increased AGE in gingival epithelium - increased Il-6 - increased sclerostin - reduction in alveolar bone loss when blocked
- 29. • Periodontitis and Diabetes are both life altering diseases • Diabetes and periodontitis are both some of the most commonly diagnosed diseases and understanding the relationship between these two is extremely important to improve the outcomes for patients • Open the door for new therapies Conclusion + Impact
- 30. Dr Scannapieco Dr Gunawardena Dr Hoekstra my fellow MA classmates Acknowledgements
- 31. QUESTIONS?