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PROBİYOTİKLER: PERİODONTOLOJİDE ANTİBİYOTİKLERE ALTERNATİF OLABİLİR Mİ?

Year 2017, Volume: 3 Issue: 1, 53 - 63, 01.04.2017

Gülbahar Ustaoğlu Elif Bilgin Esra Ercan Ali Osman Kılıç

Abstract

Periodontitis, actinomycetemcomitans, Prevotella intermedia ve Tannerella forsythia gibi gram negatif anaerobik bakterilerin ve birçok faktörün rol aldığı karmaşık bir enfeksiyondur. İltihabi periodontal hastalıkların tedavisi, zamanla patojenik hale gelen supra ve subgingival biofilmin mekanik tedavi ile uzaklaştırılma ile başlar. Bu mekanik tedaviye ek olarak antibiyotikler ve gargaralar sıklıkla kullanılmaktadır. Ancak son yıllarda antibiyotiklere karşı direnç geliştiğinden ve kullanılan bu ilaçlar oral floranın mikrobiyal dengesini bozabildiğinden dolayı alternatif yöntemler araştırılmaktadır. Probiyotikler yeterli miktarda kullanıldığında konak canlının sağlığı üzerinde yararlı etkiler oluşturan canlı mikroorganizmalardır. Önemli probiyotikler Lactobacillus ve Bifidobacterium, Escherichia, Enterococcus, Bacillus ve Streptococcus türleridir. Probiyotikler patojen bakterilerin büyüme ve gelişimini inhibe etmek, konak immün yanıtını uyarmak ve patojen bakteriler ile yer değiştirmek gibi mekanizmalar yoluyla periodontal dokular üzerinde olumlu etkilere sahiptir. Bu olumlu etkilerinden dolayı periodontal inflamasyonun tedavisinde konvansiyonel tedavilere ek olarak periodontal hastalık açısından yüksek riskli bireylerde son yıllarda koruyucu amaçlı kullanımları umut vaadetmektedir. Bu derlemede probiyotiklerin periodontal inflamasyon ve genel oral hijyenin devamlılığının sağlanmasında kullanımları güncel literatür ışığında değerlendirilmiştir

Keywords

Lactobacillus Patojen- konak etkileşimleri Periodontitis Probiyotikler

References

  • [1] Hernandez M, Dutzan N, Garcia-Sesnich J, Abusleme L, Dezerega A, Silva N, et al. Host-pathogen interactions in progressive chronic periodontitis. J Dent Res. 2011;90:1164-70.
  • [2] Paster BJ, Olsen I, Aas JA, Dewhirst FE. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol 2000. 2006;42:80-7.
  • [3] Van Winkelhoff AJ, Loos BG, van der Reijden WA, van der Velden U. Porphyromonas gingivalis, Bacteroides forsythus and other putative periodontal pathogens in subjects with and without periodontal destruction. J Clin Periodontol. 2002;29:1023-8.
  • [4] Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999;4:1-6.
  • [5] Gupta G. Probiotics and periodontal health. J Med Life. 2011;4:387-94.
  • [6] Gismondo M, Drago L, Lombardi A. Review of probiotics available to modify gastrointestinal flora. International journal of antimicrobial agents. 1999;12:287-92.
  • [7] Vasiljevic T, Shah,NP. International Dairy Journal, Probiotics—From Metchnikoff to bioactives: Elsevier; 2008. 714-28 p.
  • [8] Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis. 2001;32:1567-76.
  • [9] Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125:1401-12.
  • [10] De Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. 2008;111:1-66.
  • [11] Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME. Probiotics and immunity. J Gastroenterol. 2009;44:26-46.
  • [12] Caglar E, Kavaloglu SC, Kuscu OO, Sandalli N, Holgerson PL, Twetman S. Effect of chewing gums containing xylitol or probiotic bacteria on salivary mutans streptococci and lactobacilli. Clin Oral Investig. 2007;11:425-9.
  • [13] Arunachalam K, Gill HS, Chandra RK. Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019). Eur J Clin Nutr. 2000;54:263-7
  • [14] McDonough FE, Hitchins AD, Wong NP, Wells P, Bodwell CE. Modification of sweet acidophilus milk to improve utilization by lactose-intolerant persons. Am J Clin Nutr. 1987;45:570-4.
  • [15] Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA. 1996;275:870-6.
  • [16] Hilton E, Isenberg HD, Alperstein P, France K, Borenstein MT. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann Intern Med. 1992;116:353-7.
  • [17] Fuller R. Probiotics 2: applications and practical aspects: Springer Science & Business Media; 1997.
  • [18] Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;322:1327.
  • [19] Von Bultzingslowen I, Adlerberth I, Wold AE, Dahlen G, Jontell M. Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria. Oral Microbiol Immunol. 2003;18:278-84.
  • [20] Caglar E, Kargul B, Tanboga I. Bacteriotherapy and probiotics’ role on oral health. Oral Dis. 2005;11:131-7.
  • [21] Erickson KL, Hubbard NE. Probiotic immunomodulation in health and disease. J Nutr. 2000;130:403S-9S.
  • [22] Comelli EM, Guggenheim B, Stingele F, Neeser JR. Selection of dairy bacterial strains as probiotics for oral health. Eur J Oral Sci. 2002;110:218-24.
  • [23] Selwitz RH, Ismail AI, Pitts NB. Dental caries. Lancet. 2007;369:51-9.
  • [24] Jensen ME, Wefel JS. Effects of processed cheese on human plaque pH and demineralization and remineralization. Am J Dent. 1990;3:217-23.
  • [25] Delanghe G, Ghyselen J, van Steenberghe D, Feenstra L. Multidisciplinary breath-odour clinic. Lancet. 1997;350:187.
  • [26] Kang MS, Kim BG, Chung J, Lee HC, Oh JS. Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds. J Clin Periodontol. 2006;33:226-32.
  • [27] Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR. A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol. 2006;100:754-64.
  • [28] Takei N CK. Carranza’s Clinical Periodontology. 11th Edition ed: St. Louis, Missouri; 2012.
  • [29] Higgins TJ, Hunter N, Knox KW. Current concepts in periodontal diseases. Med J Aust. 1985;142:590-4.
  • [30] Saier MH, Jr., Mansour NM. Probiotics and prebiotics in human health. J Mol Microbiol Biotechnol. 2005;10:22-5.
  • [31] Yanine N, Araya I, Brignardello-Petersen R, Carrasco-Labra A, Gonzalez A, Preciado A, et al. Effects of probiotics in periodontal diseases: a systematic review. Clin Oral Investig. 2013;17:1627-34.
  • [32] Koll-Klais P, Mandar R, Leibur E, Marcotte H, Hammarstrom L, Mikelsaar M. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol. 2005;20:354-61.
  • [33] Sookkhee S, Chulasiri M, Prachyabrued W. Lactic acid bacteria from healthy oral cavity of Thai volunteers: inhibition of oral pathogens. J Appl Microbiol. 2001;90:172-9. [34] Bonifait L, Chandad F, Grenier D. Probiotics for oral health: myth or reality? J Can Dent Assoc. 2009;75:585-90.
  • [35] Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J. 2006;30:55-60.
  • [36] Pena JA, Rogers AB, Ge Z, Ng V, Li SY, Fox JG, et al. Probiotic Lactobacillus spp. diminish Helicobacter hepaticus-induced inflammatory bowel disease in interleukin10-deficient mice. Infect Immun. 2005;73:912-20.
  • [37] 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.
  • [38] Vivekananda MR, Vandana KL, Bhat KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial. J Oral Microbiol. 2010;2.
  • [39] Mayanagi G, Kimura M, Nakaya S, Hirata H, Sakamoto M, Benno Y, et al. Probiotic effects of orally administered Lactobacillus salivarius WB21-containing tablets on periodontopathic bacteria: a double blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2009;36:506-13.
  • [40] Szkaradkiewicz AK, Stopa J, Karpinski 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 (Warsz). 2014;62:495-500.
  • [41] 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;67:19-24.
  • [42] Staab B, Eick S, Knofler G, Jentsch H. The influence of a probiotic milk drink on the development of gingivitis: a pilot study. J Clin Periodontol. 2009;36:850-6.
  • [43] Shimauchi H, Mayanagi G, Nakaya S, Minamibuchi M, Ito Y, Yamaki K, et al. Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized, double-blind, placebo-controlled study. J Clin Periodontol. 2008;35:897-905.
  • [44] Toiviainen A, Jalasvuori H, Lahti E, Gursoy U, Salminen S, Fontana M, et al. Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults. Clin Oral Investig. 2015;19:77-83.
  • [45] 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;40:1025-35.
  • [46] Zahradnik RT, Magnusson I, Walker C, McDonell E, Hillman CH, Hillman JD. Preliminary assessment of safety and effectiveness in humans of ProBiora3, a probiotic mouthwash. J Appl Microbiol. 2009;107:682-90.
  • [47] Shah MP, Gujjari SK, Chandrasekhar VS. Evaluation of the effect of probiotic (inersan(R)) alone, combination of probiotic with doxycycline and doxycycline alone on aggressive periodontitis - a clinical and microbiological study. J Clin Diagn Res. 2013;7:595-600.
  • [48] Laleman I, Yilmaz E, Ozcelik O, Haytac C, Pauwels M, Herrero ER, et al. The effect of a streptococci containing probiotic in periodontal therapy: a randomized controlled trial. J Clin Periodontol. 2015;42:1032-41.

Year 2017, Volume: 3 Issue: 1, 53 - 63, 01.04.2017

Gülbahar Ustaoğlu Elif Bilgin Esra Ercan Ali Osman Kılıç

Abstract

Periodontitis is a complicated infection that involved by Gram-negative anaerobic bacteria, such as Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Tannerella forsythia and many other predisposing factors. The treatment of inflammatory periodontal diseases starts with mechanical removal of supra and subgingival biofilm that once becomes pathogenic by time. Antibiotics and mouthwashes are widely used in addition to these mechanical treatments. However, alternative methods to antibiotics have been investigated in recent years because of increased resistance to antibiotics and disruption of the balance of oral microbial flora. Probiotics are defined as vital microorganisms that can provide benefits on host when used in sufficient amount. Important probiotic familyof bacteria include Lactobacillus and Bifidobacterium, Escherichia, Enterococcus, Bacillus, and Streptococcus species. Probiotics have positive effects on periodontal tissues by replacement of pathogenic microorganisms in oral flora, by stimulating immune response, by interfering the growth and development of periodontal pathogens. Therefore probiotics are promising of hope because of positive effects on conventional periodontal therapy and as protective agents for high-risk individuals in terms of periodontal disease. In this review, the usage of probiotics for treatment of periodontal inflammation and maintenance of oral hygiene was evaluated considering the current literature

Keywords

Lactobacillus Pathogen-host interactions Periodontitis Probiotics

References

  • [1] Hernandez M, Dutzan N, Garcia-Sesnich J, Abusleme L, Dezerega A, Silva N, et al. Host-pathogen interactions in progressive chronic periodontitis. J Dent Res. 2011;90:1164-70.
  • [2] Paster BJ, Olsen I, Aas JA, Dewhirst FE. The breadth of bacterial diversity in the human periodontal pocket and other oral sites. Periodontol 2000. 2006;42:80-7.
  • [3] Van Winkelhoff AJ, Loos BG, van der Reijden WA, van der Velden U. Porphyromonas gingivalis, Bacteroides forsythus and other putative periodontal pathogens in subjects with and without periodontal destruction. J Clin Periodontol. 2002;29:1023-8.
  • [4] Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999;4:1-6.
  • [5] Gupta G. Probiotics and periodontal health. J Med Life. 2011;4:387-94.
  • [6] Gismondo M, Drago L, Lombardi A. Review of probiotics available to modify gastrointestinal flora. International journal of antimicrobial agents. 1999;12:287-92.
  • [7] Vasiljevic T, Shah,NP. International Dairy Journal, Probiotics—From Metchnikoff to bioactives: Elsevier; 2008. 714-28 p.
  • [8] Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis. 2001;32:1567-76.
  • [9] Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125:1401-12.
  • [10] De Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. 2008;111:1-66.
  • [11] Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME. Probiotics and immunity. J Gastroenterol. 2009;44:26-46.
  • [12] Caglar E, Kavaloglu SC, Kuscu OO, Sandalli N, Holgerson PL, Twetman S. Effect of chewing gums containing xylitol or probiotic bacteria on salivary mutans streptococci and lactobacilli. Clin Oral Investig. 2007;11:425-9.
  • [13] Arunachalam K, Gill HS, Chandra RK. Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019). Eur J Clin Nutr. 2000;54:263-7
  • [14] McDonough FE, Hitchins AD, Wong NP, Wells P, Bodwell CE. Modification of sweet acidophilus milk to improve utilization by lactose-intolerant persons. Am J Clin Nutr. 1987;45:570-4.
  • [15] Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA. 1996;275:870-6.
  • [16] Hilton E, Isenberg HD, Alperstein P, France K, Borenstein MT. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann Intern Med. 1992;116:353-7.
  • [17] Fuller R. Probiotics 2: applications and practical aspects: Springer Science & Business Media; 1997.
  • [18] Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;322:1327.
  • [19] Von Bultzingslowen I, Adlerberth I, Wold AE, Dahlen G, Jontell M. Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria. Oral Microbiol Immunol. 2003;18:278-84.
  • [20] Caglar E, Kargul B, Tanboga I. Bacteriotherapy and probiotics’ role on oral health. Oral Dis. 2005;11:131-7.
  • [21] Erickson KL, Hubbard NE. Probiotic immunomodulation in health and disease. J Nutr. 2000;130:403S-9S.
  • [22] Comelli EM, Guggenheim B, Stingele F, Neeser JR. Selection of dairy bacterial strains as probiotics for oral health. Eur J Oral Sci. 2002;110:218-24.
  • [23] Selwitz RH, Ismail AI, Pitts NB. Dental caries. Lancet. 2007;369:51-9.
  • [24] Jensen ME, Wefel JS. Effects of processed cheese on human plaque pH and demineralization and remineralization. Am J Dent. 1990;3:217-23.
  • [25] Delanghe G, Ghyselen J, van Steenberghe D, Feenstra L. Multidisciplinary breath-odour clinic. Lancet. 1997;350:187.
  • [26] Kang MS, Kim BG, Chung J, Lee HC, Oh JS. Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds. J Clin Periodontol. 2006;33:226-32.
  • [27] Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR. A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol. 2006;100:754-64.
  • [28] Takei N CK. Carranza’s Clinical Periodontology. 11th Edition ed: St. Louis, Missouri; 2012.
  • [29] Higgins TJ, Hunter N, Knox KW. Current concepts in periodontal diseases. Med J Aust. 1985;142:590-4.
  • [30] Saier MH, Jr., Mansour NM. Probiotics and prebiotics in human health. J Mol Microbiol Biotechnol. 2005;10:22-5.
  • [31] Yanine N, Araya I, Brignardello-Petersen R, Carrasco-Labra A, Gonzalez A, Preciado A, et al. Effects of probiotics in periodontal diseases: a systematic review. Clin Oral Investig. 2013;17:1627-34.
  • [32] Koll-Klais P, Mandar R, Leibur E, Marcotte H, Hammarstrom L, Mikelsaar M. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol. 2005;20:354-61.
  • [33] Sookkhee S, Chulasiri M, Prachyabrued W. Lactic acid bacteria from healthy oral cavity of Thai volunteers: inhibition of oral pathogens. J Appl Microbiol. 2001;90:172-9. [34] Bonifait L, Chandad F, Grenier D. Probiotics for oral health: myth or reality? J Can Dent Assoc. 2009;75:585-90.
  • [35] Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J. 2006;30:55-60.
  • [36] Pena JA, Rogers AB, Ge Z, Ng V, Li SY, Fox JG, et al. Probiotic Lactobacillus spp. diminish Helicobacter hepaticus-induced inflammatory bowel disease in interleukin10-deficient mice. Infect Immun. 2005;73:912-20.
  • [37] 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.
  • [38] Vivekananda MR, Vandana KL, Bhat KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial. J Oral Microbiol. 2010;2.
  • [39] Mayanagi G, Kimura M, Nakaya S, Hirata H, Sakamoto M, Benno Y, et al. Probiotic effects of orally administered Lactobacillus salivarius WB21-containing tablets on periodontopathic bacteria: a double blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2009;36:506-13.
  • [40] Szkaradkiewicz AK, Stopa J, Karpinski 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 (Warsz). 2014;62:495-500.
  • [41] 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;67:19-24.
  • [42] Staab B, Eick S, Knofler G, Jentsch H. The influence of a probiotic milk drink on the development of gingivitis: a pilot study. J Clin Periodontol. 2009;36:850-6.
  • [43] Shimauchi H, Mayanagi G, Nakaya S, Minamibuchi M, Ito Y, Yamaki K, et al. Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized, double-blind, placebo-controlled study. J Clin Periodontol. 2008;35:897-905.
  • [44] Toiviainen A, Jalasvuori H, Lahti E, Gursoy U, Salminen S, Fontana M, et al. Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults. Clin Oral Investig. 2015;19:77-83.
  • [45] 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;40:1025-35.
  • [46] Zahradnik RT, Magnusson I, Walker C, McDonell E, Hillman CH, Hillman JD. Preliminary assessment of safety and effectiveness in humans of ProBiora3, a probiotic mouthwash. J Appl Microbiol. 2009;107:682-90.
  • [47] Shah MP, Gujjari SK, Chandrasekhar VS. Evaluation of the effect of probiotic (inersan(R)) alone, combination of probiotic with doxycycline and doxycycline alone on aggressive periodontitis - a clinical and microbiological study. J Clin Diagn Res. 2013;7:595-600.
  • [48] Laleman I, Yilmaz E, Ozcelik O, Haytac C, Pauwels M, Herrero ER, et al. The effect of a streptococci containing probiotic in periodontal therapy: a randomized controlled trial. J Clin Periodontol. 2015;42:1032-41.
There are 47 citations in total.

Details

Other ID JA44SZ55GZ
Journal Section Research Article
Authors

Gülbahar Ustaoğlu This is me

Elif Bilgin This is me

Esra Ercan This is me

Ali Osman Kılıç This is me

Publication Date April 1, 2017
Submission Date April 1, 2017
Published in Issue Year 2017 Volume: 3 Issue: 1

Cite

Vancouver Ustaoğlu G, Bilgin E, Ercan E, Kılıç AO. PROBİYOTİKLER: PERİODONTOLOJİDE ANTİBİYOTİKLERE ALTERNATİF OLABİLİR Mİ?. Aydin Dental Journal. 2017;3(1):53-6.

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