The Effect of Multi Probiotic Supplementation on Serum Tumor Necrosis Factor Alpha Levels in Experimental Periodontitis

Abstract

Objective: Probiotics, which are beneficial microorganisms on health, take part in periodontal disease pathogenesis by affecting immune system and pathogenic flora. Probiotic supplementation was shown to improve clinical periodontal parameters and decrease alveolar bone loss (ABL) in experimental studies. Tumor necrosis factor alpha (TNFα) is one of the key cytokines responsible for destruction of periodontal soft and hard tissues. The aim of this study was to evaluate the effects of multi probiotic supplementation containing Lactobacillus, Bifidobacterium, and Streptococcus species on ABL and serum TNFα levels. Material-Method: Twenty-four 6-8 weeks adult Wistar albino rat were separated equally (n=8) into control (C), ligature-induced periodontitis (Lig), and probiotic administration additionally to ligature-induced periodontitis (VSL). All rats were fed with standard water and diet for 44 days; additionally multi probiotics were supplemented to the rats in VSL group via oral gavage in 1 ml saline. Periodontitis was induced using ligature to the maxillary 2nd molars of the rats in Lig and VSL groups 2 weeks before the end of the study. ABL was measured histomorphometrically and serum TNFa levels were analysed with ELISA. Results: ABL increased in the ligature-induced periodontitis groups (Lig and VSL), compared to C group, and decreased in VSL group, in comparison with the Lig group (p<0.05). Serum TNFα levels were significantly higher in Lig group than C group, and significantly lower in VSL group than Lig group (p<0.05). Conclusions: We suggest that multi probiotic supplementation could inhibit periodontal bone destruction by decreasing serum TNFα levels in an experimental periodontitis model.

Keywords

• Probiotics
• Experimental Periodontitis
• Tumor Necrosis Factor Alpha

Deneysel Periodontitiste Çoklu Probiyotik Desteğinin Serum Tümör Nekroz Faktör Alfa Seviyelerine Etkisi

Abstract

Amaç: Probiyotikler sağlığa yararlı mikroorganizmalar olup immün sistemi ve patojenik florayı etkileyerek periodontal hastalık patogenezinde yer almaktadır. Probiyotik desteğinin klinik periodontal parametreleri iyileştirdiği ve deneysel çalışmalarda alveoler kemik kaybını (AKK) azaltabileceği gösterilmiştir. Tümör nekroz faktör alfa (TNFα) periodontal sert ve yumuşak doku yıkımdan sorumlu anahtar sitokinlerden birisidir. Bu çalışmanın amacı Lactobacillus, Bifidobacterium ve Streptococcus suşlarını içeren çoklu probiyotik desteğinin AKK ve serum TNFα seviyelerine olan etkilerini incelemektir. Materyal-Metot: Yirmi dört adet 6-8 haftalık yetişkin Wistar albino rat eşit sayıda (n=8) kontrol (K), ligatürle indüklenen periodontitis (Lig) ve ligatürle indüklenen periodontitise ek probiyotik desteği (VSL) gruplarına ayrılmıştır. Bütün ratlar 44 gün süresince standart yem ve su içeren diyetle beslenmiş, VSL grubundaki ratlara ayrıca oral gavajla 1 ml serum içerisinde çoklu probiyotik desteği uygulanmıştır. Deney bitiminden 2 hafta önce Lig ve VSL grubundaki ratların maksillar 2. molar dişlerine ligatür kullanılarak periodontitis indüklenmiştir. AKK histomorfometrik olarak ölçülmüş, serum TNFα seviyeleri ELISA ile incelenmiştir. Bulgular: AKK, K grubuna göre ligatürle periodontitis indüklenen gruplarda (Lig ve VSL) artmış, VSL grubunda Lig grubuna kıyasla azalmıştır (p<0,05). Serum TNFα seviyeleri, Lig grubunda K grubuyla karşılaştırıldığında anlamlı derecede yükselmiş, VSL grubunda ise Lig grubuna göre anlamlı derecede azalmıştır (p<0,05). Sonuç: Deneysel periodontitis modelinde çoklu probiyotik desteğinin serum TNFα seviyelerini azaltarak periodontal kemik yıkımını engelleyebileceği düşünülmektedir.

Keywords

• Probiyotikler
• Deneysel Periodontitis
• Tümör Nekroz Faktör Alfa

References

1. 1. Kantarci A, Hasturk H, Van Dyke TE. Host-mediated resolution of inflammation in periodontal diseases. Periodontol 2000. 2006;40:144-63.
2. 2. Berezow AB, Darveau RP. Microbial shift and periodontitis. Periodontol 2000. 2011;55(1):36-47.
3. 3. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-14.
4. 4. Gionchetti P, Lammers KM, Rizzello F, Campieri M. VSL#3: an analysis of basic and clinical contributions in probiotic therapeutics. Gastroenterol Clin North Am. 2005;34(3):499-513.
5. 5. Teughels W, Loozen G, Quirynen M. Do probiotics offer opportunities to manipulate the periodontal oral microbiota? J Clin Periodontol. 2011;38(Suppl. 11):159-77.
6. 6. Graves DT, Cochran D. The contribution of interleukin‐1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003;74(3):391-401.
7. 7. Li L, Yang G, Shi S, Yang M, Liu H, Boden G. The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo. Cytokine. 2009;45(1):12-9.
8. 8. Sima C, Paster B, Van Dyke TE. Function of Pro-Resolving Lipid Mediator Resolvin E1 in Type 2 Diabetes. Crit Rev Immunol. 2018;38(5):343-65.

9. 9. Gomes FI, Aragao MG, Barbosa FC, Bezerra MM, de Paulo Teixeira Pinto V, Chaves HV. Inflammatory cytokines interleukin-1beta and tumour necrosis factor-alpha - novel biomarkers for the detection of periodontal diseases: a literature review. J Oral Maxillofac Res. 2016;7(2):e2.
10. 10. Gumus P, Nizam N, Lappin DF, Buduneli N. Saliva and serum levels of B-cell activating factors and tumor necrosis factor-alpha in patients with periodontitis. J Periodontol. 2014;85(2):270-80.
11. 11. Yigit U, Kirzioglu FY, Uguz AC, Naziroglu M, Ozmen O. Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis? Arch Oral Biol. 2017;81:61-8.
12. 12. Stamatova I, Meurman JH. Probiotics and periodontal disease. Periodontol 2000. 2009;51:141-51.
13. 13. Riccia DN, Bizzini F, Perilli MG, Polimeni A, Trinchieri V, Amicosante G, et al. Anti-inflammatory effects of lactobacillus brevis (CD2) on periodontal disease. Oral Dis. 2007;13(4):376-85.
14. 14. Ince G, Gursoy H, Ipci SD, Cakar G, Emekli-Alturfan E, Yilmaz S. Clinical and biochemical evaluation of lozenges containing lactobacillus reuteri as an adjunct to non-surgical periodontal therapy in chronic periodontitis. J Periodontol. 2015;86(6):746-54.
15. 15. Tekce M, Ince G, Gursoy H, Dirikan Ipci S, Cakar G, Kadir T, et al. Clinical and microbiological effects of probiotic lozenges in the treatment of chronic periodontitis: a 1-year follow-up study. J Clin Periodontol. 2015;42(4):363-72.
16. 16. Foureaux Rde C, Messora MR, de Oliveira LF, Napimoga MH, Pereira AN, Ferreira MS, et al. Effects of probiotic therapy on metabolic and inflammatory parameters of rats with ligature-induced periodontitis associated with restraint stress. J Periodontol. 2014;85(7):975-83.
17. 17. Messora MR, Pereira LJ, Foureaux R, Oliveira LF, Sordi CG, Alves AJ, et al. Favourable effects of Bacillus subtilis and Bacillus licheniformis on experimental periodontitis in rats. Arch Oral Biol. 2016;66:108-19.
18. 18. Garcia VG, Knoll LR, Longo M, Novaes VC, Assem NZ, Ervolino E, et al. Effect of the probiotic saccharomyces cerevisiae on ligature-induced periodontitis in rats. J Periodontal Res. 2016;51(1):26-37.
19. 19. Maekawa T, Hajishengallis G. Topical treatment with probiotic Lactobacillus brevis CD2 inhibits experimental periodontal inflammation and bone loss. J Periodontal Res. 2014;49(6):785-91.
20. 20. Oliveira LF, Salvador SL, Silva PH, Furlaneto FA, Figueiredo L, Casarin R, et al. Benefits of bifidobacterium animalis subsp. lactis probiotic in experimental periodontitis. J Periodontol. 2017;88(2):197-208.
21. 21. Szkaradkiewicz AK, Stopa J, Karpiński TM. Effect of oral administration involving a probiotic strain of Lactobacillus reuteri on pro-inflammatory cytokine response in patients with chronic periodontitis. Arch Immunol Ther Exp. 2014;62(6):495-500.
22. 22. Twetman S, Derawi B, Keller M, Ekstrand K, Yucel-Lindberg T, Stecksen-Blicks C. Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid. Acta Odontol Scand. 2009;67(1):19-24.
23. 23. Kaynak D, Meffert R, Gunhan M, Gunhan O, Ozkaya O. A histopathological investigation on the effects of the bisphosphonate alendronate on resorptive phase following mucoperiosteal flap surgery in the mandible of rats. J Periodontol. 2000;71(5):790-6.
24. 24. Kuo PJ, Hung TF, Lin CY, Hsiao HY, Fu MW, Hong PD, et al. Carvacrol ameliorates ligation-induced periodontitis in rats. J Periodontol. 2017;88(7):e120-e8.
25. 25. Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. J Nutr. 2009;139(5):905-11.
26. 26. Kirzioglu FY, Ozmen O, Dogan B, Bulut MT, Fentoglu O, Ozdem M. Effects of rosuvastatin on inducible nitric oxide synthase in rats with hyperlipidaemia and periodontitis. J Periodontal Res. 2018;53(2):258-66.
27. 27. Taskan MM, Balci Yuce H, Karatas O, Gevrek F, Toker H. Evaluation of the effect of oleuropein on alveolar bone loss, inflammation, and apoptosis in experimental periodontitis. J Periodontal Res. 2019;54(6):624-32.
28. 28. Oz HS, Puleo DA. Animal models for periodontal disease. J Biomed Biotechnol. 2011;2011:754857.
29. 29. de Molon RS, Mascarenhas VI, de Avila ED, Finoti LS, Toffoli GB, Spolidorio DM, et al. Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice. Clin Oral Investig. 2016;20(6):1203-16.
30. 30. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242-9.
31. 31. Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7(4):2839-49.
32. 32. Yoo JY, Kim SS. Probiotics and prebiotics: present status and future perspectives on metabolic disorders. Nutrients. 2016;8(3):173.
33. 33. Joffre C, Dinel AL, Aubert A, Fressange-Mazda C, Le Ruyet P, Laye S. Impact of Lactobacillus fermentum and dairy lipids in the maternal diet on the fatty acid composition of pups' brain and peripheral tissues. Prostaglandins Leukot Essent Fatty Acids. 2016;115:24-34.
34. 34. Kaplas N, Isolauri E, Lampi AM, Ojala T, Laitinen K. Dietary counseling and probiotic supplementation during pregnancy modify placental phospholipid fatty acids. Lipids. 2007;42(9):865-70.
35. 35. Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M, Haytac MC. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol. 2013;40(11):1025-35.
36. 36. Montero E, Iniesta M, Rodrigo M, Marin MJ, Figuero E, Herrera D, et al. Clinical and microbiological effects of the adjunctive use of probiotics in the treatment of gingivitis: a randomized controlled clinical trial. J Clin Periodontol. 2017;44(7):708-16.
37. 37. Pelekos G, Ho SN, Acharya A, Leung WK, McGrath C. A double-blind, paralleled-arm, placebo-controlled and randomized clinical trial of the effectiveness of probiotics as an adjunct in periodontal care. J Clin Periodontol. 2019;46(12):1217-27.
38. 38. Ulisse S, Gionchetti P, D’Alò S, Russo FP, Pesce I, Ricci G, et al. Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: effects of probiotic treatment. Am J Gastroenterol. 2001;96(9):2691-9.
39. 39. Loguercio C, Federico A, Tuccillo C, Terracciano F, D'Auria MV, De Simone C, et al. Beneficial effects of a probiotic VSL# 3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol. 2005;39(6):540-3.
40. 40. Imperial IC, Ibana JA. Addressing the Antibiotic Resistance Problem with Probiotics: Reducing the Risk of Its Double-Edged Sword Effect. Front Microbiol. 2016;7:1983.