Association between Aggregatibacter actinomy-cetemcomitans bacterial load and NLRP3 inflam-masome activation in periodontitis patients with Diabetes

Mohammed J. al-obaidi; Batool H. Al-Ghurabi

doi:10.32007/jfacmedbagdad.6441972

Authors

Mohammed J. al-obaidi Department of basic science of Oral Microbiology, College of Dentistry, University of Baghdad.
Batool H. Al-Ghurabi Department of basic science of Oral Microbiology, College of Dentistry, University of Baghdad.

DOI:

https://doi.org/10.32007/jfacmedbagdad.6441972

Keywords:

Aggregatibacter actinomycetemcomitans, periodontitis, type 2 DM, inflammasome, NLRP3.

Abstract

Background: Aggregatibacter actinomycetemcomitans is one of the most common periodontal pathogen that has a direct effect on periodontium. Diabetes and periodontitis considered as chronic diseases with a bidirectional relationship between them. Evidence has shown that the Node Like Receptor Pyrine-3 inflammasome, is crucial for both illnesses.

Objectives: This investigation was conducted to observe the association between bacterial load of A. actinomyctecomtans and serum level of NLRP3 inflammasome in periodontitis patient with and without type 2 DM and control group.

Materials and Methods: This case-control study included 85 participants, whose ages ranged from (23-55) years. Split into three groups; the control group, which had a clinically and systemically healthy periodontium, and the two groups with periodontitis, one of which also had type 2 DM. Samples of the four most profound periodontal pockets were sampled for subgingival plaque, and from the gingival sulcus in the control group. The real-time (PCR) was utilized in this experiment. to quantify A. actinomyctecomtans DNA was isolated from samples of dental plaque. All subjects' serum was collected, and the concentration of NLRP3 was measured using an ELISA technique.

Results: The results showed that the bacterial count was higher in two groups of patient than the control group, but there were no-significant differences. On the other hand, there was a significant correlation between the bacterial count and periodontal parameters in periodontitis with type 2 DM group, while in periodontitis group there was positive correlation with clinical attachment loss and bleeding on probing. A significant positive correlation also noticed between NLRP3 inflammasome and periodontal parameters in periodontitis patient with type2 DM. Regarding the group of periodontitis patients without systemic disease there was no significance correlation between inflammasome and clinical parameters. Finally, there is a non-significant correlation of A. actinomyctecomtans with inflammasome.

Conclusions: A. actinomyctecomtans detection rate was strongly higher in patient groups compared to healthy subjects but statically non-significant. Moreover, the lack of correlation between A. actinomyctecomtans and the NLRP3 inflammasome indicates that NLRP3 activation is associated with inflammatory processes that are induced by a number of external factors, other than bacteria.

Downloads

Download data is not yet available.

References

Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nature reviews Disease pri-mers. 2017 Jun 22;3(1):1-4.

Kinane DF, Demuth DR, Gorr SU, Hajishengallis GN, Martin MH. Human variability in innate immun-ity. Periodontology 2000. 2007 Oct;45(1):14-34.

Amano A. Bacterial adhesins to host components in periodontitis. Periodontology 2000. 2010; 52:12-37.

Liang S, Krauss JL, Domon H, McIntosh ML, Ho-sur KB, Qu H, Li F, Tzekou A, Lambris JD, Hajishen-gallis G. The C5a receptor impairs IL-12–dependent clearance of Porphyromonas gingivalis and is re-quired for induction of periodontal bone loss. The Journal of immunology. 2011 Jan 15;186(2):869-77.

Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host re-sponse. Trends in immunology. 2014 Jan 1;35(1):3-11.

Socransky SS, Haffajee AD, Cugini MA, Smith CK, Kent Jr RL. Microbial complexes in subgingival plaque. Journal of clinical periodontology. 1998 Feb;25(2):134-44.

Tang-Siegel G, Bumgarner R, Ruiz T, Kittichot-irat W, Chen W, Chen C. Human serum-specific acti-vation of alternative sigma factors, the stress re-sponders in Aggregatibacter actinomycetemcomi-tans. PloS one. 2016 Aug 4;11(8):e0160018.

Fives-Taylor PM, Meyer DH, Mintz KP, Brissette C. Virulence factors of Actinobacillus actinomy-cetemcomitans. Periodontology 2000. 1999 Jun 1;20:136-67.

Henderson B, Wilson M, Sharp L, Ward JM. Ac-tinobacillus actinomycetemcomitans. Journal of med-ical microbiology. 2002 Dec 1;51(12):1013-20.

Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes research and clinical practice. 2017 Jun 1;128:40-50.

McPhee SJ, Papadakis MA. Diabetes Mellitus and Hyperglycemia: Current Medical Diagnosis & Treatment. 49th Edition. 2010; 1079-1133.

Harish S, Shantaram M. A comparative and cor-relative study between blood and salivary glucose with blood HbA1c IN type 2 diabetes. Int J Pharm Sci Res. 2019 Jan 1;10(1):401-6.

AL-Azawy VS, Sh A, Al-Ghurabi BH. A compara-tive study on serum leptin and adiponectin levels in periodontitis patients with and without diabetes Mellitus Type 2. Microbiology. 2014 May;3(5):1-4.

Khanuja PK, Narula SC, Rajput R, Sharma RK, Tewari S. Association of periodontal disease with gly-cemic control in patients with type 2 diabetes in In-dian population. Frontiers of medicine. 2017 Mar;11(1):110-9.

Alasqah M, Mokeem S, Alrahlah A, Al-Hamoudi N, Abduljabbar T, Akram Z, Vohra F, Javed F. Peri-odontal parameters in prediabetes, type 2 diabetes mellitus, and non-diabetic patients. Brazilian oral re-search. 2018 Aug 6;32.

Abdul-wahab GA, Ahmed MA. Assessment of Some Salivary Enzymes Levels in Type 2 Diabetic Pa-tients with Chronic Periodontitis: Clinical and Bio-chemical Study. Journal of baghdad college of den-tistry. 2015 Mar;325(2218):1-3.

Sanz M, Ceriello A, Buysschaert M, Chapple I, Demmer RT, Graziani F, Herrera D, Jepsen S, Lione L, Madianos P, Mathur M. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint work-shop on periodontal diseases and diabetes by the In-ternational Diabetes Federation and the European Federation of Periodontology. Diabetes research and clinical practice. 2018 Mar 1;137:231-41.

Buduneli N. Hyperglycemia and periodontitis: Possible mechanisms of interaction. Oral diseases. 2018 Sep 21;25(4):925-7.

Tsai C, Hayes C, Taylor GW. Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community dentistry and oral epidemiology. 2002 Jun;30(3):182-92.

Serrano C, Perez C, Rodríguez M. Periodontal conditions in a group of Colombian type 2 diabetic patients with different degrees of metabolic control. Acta odontológica latinoamericana. 2012 Apr;25(1):130-7.

Awad F, Assrawi E, Jumeau C, Georgin-Lavialle S, Cobret L, Duquesnoy P, Piterboth W, Thomas L, Stankovic-Stojanovic K, Louvrier C, Giurgea I. Im-pact of human monocyte and macrophage polariza-tion on NLR expression and NLRP3 inflammasome activation. PloS one. 2017 Apr 12;12(4):e0175336.

Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activa-tion and regulation. International journal of molecu-lar sciences. 2019 Jul 6;20(13):3328.

Lv K, Wang G, Shen C, Zhang X, Yao H. Role and mechanism of the nod-like receptor family pyrin do-main-containing 3 inflammasome in oral disease. Ar-chives of Oral Biology. 2019 Jan 1;97:1-1.

Lang, N. P. (1999). International classification workshop. Consensus report: Aggressive periodonti-tis. Ann Periodontol, 4, 53.

Borges MA, Figueiredo LC, Brito Jr RB, Faveri M, Feres M. Microbiological composition associated with vitamin D receptor gene polymorphism in chronic periodontitis. Brazilian Oral Research. 2009;23:203-8.

Byrne SJ, Dashper SG, Darby IB, Adams GG, Hoffmann B, Reynolds EC. Progression of chronic periodontitis can be predicted by the levels of Por-phyromonas gingivalis and Treponema denticola in subgingival plaque. Oral microbiology and immunol-ogy. 2009 Dec;24(6):469-77.

Charalampakis G, Dahlén G, Carlén A, Leon-hardt Å. Bacterial markers vs. clinical markers to predict progression of chronic periodontitis: A 2‐yr prospective observational study. European journal of oral sciences. 2013 Oct;121(5):394-402.

Tomás I, Regueira-Iglesias A, López M, Arias-Bu-janda N, Novoa L, Balsa-Castro C, Tomás M. Quan-tification by qPCR of pathobionts in chronic perio-dontitis: development of predictive models of disease severity at site-specific level. Frontiers in microbiol-ogy. 2017 Aug 9;8:1443.

Castrillon CA, Hincapie JP, Yepes FL, Roldan N, Moreno SM, Contreras A, Botero JE. Occurrence of red complex microorganisms and A ggregatibacter actinomycetemcomitans in patients with diabetes. Journal of investigative and clinical dentistry. 2015 Feb;6(1):25-31.

Sánchez GA, Acquier AB, De Couto A, Busch L, Mendez CF. Association between Aggregatibacter actinomycetemcomitans and Porphyromonas gingi-valis in subgingival plaque and clinical parameters, in Argentine patients with aggressive periodontitis. Microbial pathogenesis. 2015 May 1;82:31-6.

Tomita S, Komiya-Ito A, Imamura K, Kita D, Ota K, Takayama S, Makino-Oi A, Kinumatsu T, Ota M, Saito A. Prevalence of Aggregatibacter actinomy-cetemcomitans, Porphyromonas gingivalis and Tan-nerella forsythia in Japanese patients with general-ized chronic and aggressive periodontitis. Microbial pathogenesis. 2013 Aug 1;61:11-5.

Gholizadeh P, Pormohammad A, Eslami H, Sho-kouhi B, Fakhrzadeh V, Kafil HS. Oral pathogenesis of Aggregatibacter actinomycetemcomitans. Micro-bial pathogenesis. 2017 Dec 1;113:303-11.

Kim Y, Wang W, Okla M, Kang I, Moreau R, Chung S. Suppression of NLRP3 inflammasome by γ-tocotrienol ameliorates type 2 diabetes. Journal of li-pid research. 2016 Jan 1;57(1):66-76.

García‐Hernández AL, Muñoz‐Saavedra ÁE, González‐Alva P, Moreno‐Fierros L, Llamosas‐Her-nández FE, Cifuentes‐Mendiola SE, Rubio‐Infante N. Upregulation of proteins of the NLRP3 inflam-masome in patients with periodontitis and uncon-trolled type 2 diabetes. Oral Diseases. 2019 Mar;25(2):596-608.

Higuchi K, Ziauddin SM, Yamashita Y, Ozaki Y, Yoshimura A. Initial periodontal treatment affects nu-cleotide-binding domain leucine-rich repeat-contain-ing protein 3 inflammasome priming in peripheral blood mononuclear cells. Archives of Oral Biology. 2020 Feb 1;110:104625.

Aral K, Berdeli E, Cooper PR, Milward MR, Ka-pila Y, Karadede Ünal B, Aral CA, Berdeli A. Differ-ential expression of inflammasome regulatory tran-scripts in periodontal disease. Journal of Periodon-tology. 2020 May;91(5):606-16.

Shahbeik S, Taleghani F, Sattari M, Mohammadi MM, Moravej M. Evaluation of NLRP3 and IL-18 Levels after Periodontal Therapy NLRP3 and IL-18 Levels after Periodontal Therapy. Iranian Journal of Allergy, Asthma and Immunology. 2021;20(6):764.

Surlin P, Lazar L, Sincar C, Gheorghe DN, Popescu DM, Boldeanu VM, Pitru A, Florescu C, Rogoveanu I. NLRP3 Inflammasome Expression in Gingival Crevicular Fluid of Patients with Periodon-titis and Chronic Hepatitis C. Mediators of Inflamma-tion. 2021 Nov 19;2021.

Lamont RJ, Hajishengallis G. Polymicrobial syn-ergy and dysbiosis in inflammatory disease. Trends in molecular medicine. 2015 Mar 1;21(3):172-83.

Lamont RJ, Koo H, Hajishengallis G. The oral mi-crobiota: dynamic communities and host interac-tions. Nature reviews microbiology. 2018 Dec;16(12):745-59.

Yilmaz Ö, Sater AA, Yao L, Koutouzis T, Petten-gill M, Ojcius DM. ATP‐dependent activation of an inflammasome in primary gingival epithelial cells in-fected by Porphyromonas gingivalis. Cellular micro-biology. 2010 Feb;12(2):188-98.