Periodontal Hastalıklarda Probiyotikler: Mekanizmalar, Klinik Etkiler ve Terapötik Potansiyel
Özet
Periodontal hastalıklar, dental plak biyofilmine karşı gelişen konak immün-inflamatuar yanıtın yönlendirdiği kronik ve multifaktöriyel hastalıklardır. Güncel patogenez modelleri, periodontitisin yalnızca mikrobiyal yük ile değil; disbiyotik mikrobiyota, konak yanıtı ve çevresel faktörlerin etkileşimi ile ortaya çıktığını göstermektedir. Konvansiyonel periodontal tedavinin temelini mekanik biyofilm eliminasyonu oluştursa da, anatomik sınırlılıklar, patojen rekolonizasyonu ve sistemik risk faktörleri tedavi başarısını sınırlayabilmektedir. Bu durum, periodontal tedavide ekolojik ve biyolojik hedeflere yönelik adjuvan yaklaşımlara olan ilgiyi artırmıştır. Probiyotikler, oral mikrobiyal ekosistemi modüle etme ve konak inflamatuar yanıtını düzenleme potansiyelleri nedeniyle periodontal hastalıkların yönetiminde umut verici biyolojik ajanlar olarak değerlendirilmektedir. Probiyotiklerin antibakteriyel metabolit üretimi, biyofilm modülasyonu, mikrobiyal rekabet, epitel bariyer fonksiyonunun desteklenmesi ve immünomodülasyon gibi çok katmanlı etki mekanizmalarına sahip olduğu gösterilmiştir. Klinik çalışmalar, özellikle Lactobacillus reuteri ve Bifidobacterium animalis gibi belirli suşların scaling–root planing’e adjuvan olarak kullanıldığında bazı periodontal parametrelerde ek klinik fayda sağlayabileceğini bildirmektedir. Bununla birlikte mevcut kanıtlar heterojen olup, probiyotiklerin rutin periodontal tedavide standart kullanımını desteklemek için daha yüksek kalitede ve uzun dönemli klinik çalışmalara ihtiyaç vardır.
Periodontal diseases are chronic and multifactorial inflammatory conditions driven by host immune responses to dental plaque biofilm. Contemporary pathogenic models indicate that periodontitis results not merely from microbial accumulation but from complex interactions among dysbiotic microbiota, host immune responses, and environmental factors. Although mechanical biofilm removal remains the cornerstone of conventional periodontal therapy, anatomical limitations, bacterial recolonization, and systemic risk factors may restrict treatment success. These limitations have increased interest in adjunctive therapeutic strategies targeting biological and ecological mechanisms. Probiotics have emerged as promising biological agents in periodontal therapy due to their potential to modulate the oral microbial ecosystem and regulate host inflammatory responses. Their effects involve multiple mechanisms, including production of antimicrobial metabolites, biofilm modulation, microbial competition, enhancement of epithelial barrier integrity, and immunomodulatory activity. Clinical studies suggest that certain strains, particularly Lactobacillus reuteri and Bifidobacterium animalis, may provide additional clinical benefits when used as adjuncts to scaling and root planing. However, current evidence remains heterogeneous, and further well-designed, long-term clinical trials are required to clarify the effectiveness, optimal protocols, and clinical indications of probiotic therapy in periodontology.
Referanslar
GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries, 1990–2016. Lancet. 2017;390:1211-59.
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366:1809-20.
Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038.
Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global prevalence of periodontal disease and lack of its surveillance. Sci World J. 2020;2020:2146160.
Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 2021;21:426-40.
Cardoso EM, Reis C, Manzanares-Céspedes MC. Chronic periodontitis and systemic diseases. Postgrad Med. 2018;130:98-104.
Cobb CM. Clinical significance of non-surgical periodontal therapy. J Clin Periodontol. 2002;29:6-16.
Aimetti M. Nonsurgical periodontal treatment. Int J Esthet Dent. 2014;9:251-67.
Haffajee AD, Teles RP, Socransky SS. Effect of periodontal therapy on subgingival microbiota. Periodontol 2000. 2006;42:219-58.
Jepsen K, Jepsen S. Antibiotics/antimicrobials in periodontal therapy. Periodontol 2000. 2016;71:82-112.
Rams TE, Degener JE, van Winkelhoff AJ. Antibiotic resistance in chronic periodontitis. J Periodontol. 2014;85:160-9.
Yoon MY, Yoon SS. Disruption of the gut ecosystem by antibiotics. Yonsei Med J. 2018;59:4-12.
FAO/WHO Working Group. Guidelines for the evaluation of probiotics in food. Report of a joint FAO/WHO working group. London, Ontario, Canada: Food and Agriculture Organization of the United Nations and World Health Organization; 2002.
Teughels W, Loozen G, Quirynen M. Probiotics and periodontal microbiota. J Clin Periodontol. 2011;38:159-77.
Seminario-Amez M, López-López J, Estrugo-Devesa A, Ayuso-Montero R, Jané-Salas E. Probiotics and oral health: a systematic review. Med Oral Patol Oral Cir Bucal. 2017;22:e282-8.
Pelekos G, Ho SN, Acharya A, Leung WK, McGrath C, Chatfield M, et al. Probiotics as adjuncts to non-surgical periodontal therapy: a systematic review and meta-analysis. J Clin Periodontol. 2019;46:1217-28.
Ho SN, Acharya A, Sahrmann P, Lewis K, Lau E, Paju S, et al. Probiotics as adjuncts to non-surgical periodontal therapy: systematic review and meta-analysis. J Evid Based Dent Pract. 2020;20:101397.
Ikram S, Hassan N, Raffat MA, Mirza S, Akram Z. Adjunctive probiotic therapy in chronic periodontitis: a systematic review and meta-analysis. J Investig Clin Dent. 2018;9:e12338.
Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, et al. The subgingival microbiome in health and periodontitis. ISME J. 2013;7:1016-25.
Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, et al. Distinct and complex bacterial profiles in human periodontitis and health. ISME J. 2012;6:1176-85.
Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontol 2000. 2020;83:14-25.
Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16:745-59.
Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25:134-44.
Hajishengallis G, Lamont RJ. Polymicrobial synergy and dysbiosis in inflammatory disease. Mol Oral Microbiol. 2012;27:409-19.
Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in periodontitis. Periodontol 2000. 2014;64:57-80.
Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity. 2017;46:562-76.
Ince G, Gursoy H, Ipci SD, Cakar G, Emekli-Alturfan E, Yilmaz S. Clinical and microbiological effects of Lactobacillus reuteri in non-surgical periodontal therapy. J Periodontol. 2015;86:746-54.
Kuru BE, Laleman I, Yalnizoglu T, Kuru L, Teughels W. Influence of Bifidobacterium animalis probiotic on gingival health. J Periodontol. 2017;88:1115-23.
Invernici MM, Salvador SL, Silva PHF, Soares MSM, Casarin RCV, Palioto DB, et al. Effects of Bifidobacterium animalis subsp. lactis HN019 in chronic periodontitis. PLoS One. 2020;15:e0238425.
Flichy-Fernández AJ, Ata-Ali J, Alegre-Domingo T, Candel-Martí E, Ata-Ali F, Palacio J. Effect of Lactobacillus reuteri in peri-implant mucositis. J Periodontal Res. 2015;50:775-85.
Laleman I, Pauwels M, Quirynen M, Teughels W. Probiotics in peri-implantitis therapy. Clin Oral Implants Res. 2020;31:84-92.
Page RC, Kornman KS. The pathogenesis of human periodontitis. Periodontol 2000. 1997;14:9-11.
Hajishengallis G. Immune evasion strategies of Porphyromonas gingivalis. J Oral Biosci. 2011;53:233-40.
Lamont RJ, Hajishengallis G. Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med. 2015;21:172-83.
Marsh PD. Microbial ecology of dental plaque. Adv Dent Res. 1994;8:263-71.
Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000. 2006;42:180-218.
Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8:623-33.
Slots J. Periodontal pathogens. Periodontol 2000. 2002;28:56-71.
Holt SC, Ebersole JL. Porphyromonas gingivalis virulence factors. Periodontol 2000. 2005;38:22-38.
Fine DH, Schreiner H, Velusamy S. Aggregatibacter actinomycetemcomitans and aggressive periodontitis. Periodontol 2000. 2014;65:97-114.
Guo Y, Nguyen KA, Potempa J. Gingipains and periodontal disease. Periodontol 2000. 2010;54:79-99.
Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010;8:481-90.
Hajishengallis G, Lambris JD. Complement and dysbiosis in periodontal disease. Trends Immunol. 2011;32:310-18.
Heitz-Mayfield LJA, Lang NP. Surgical and non-surgical periodontal therapy. Periodontol 2000. 2013;62:68-86.
Bower RC. Furcation morphology relative to periodontal therapy. J Periodontol. 1979;50:366-74.
Bergström J. Smoking and periodontal disease. J Clin Periodontol. 2004;31:404-11.
Taylor GW, Borgnakke WS. Periodontal disease and diabetes. Periodontol 2000. 2008;44:127-53.
Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Berglundh T, et al. Treatment of stage I–III periodontitis. J Clin Periodontol. 2020;47(Suppl 22):4-60.
Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. ISAPP consensus statement on probiotics. Nat Rev Gastroenterol Hepatol. 2014;11:506-14.
Sanders ME. Probiotics: definition, sources, selection. Clin Infect Dis. 2008;46(Suppl 2):S58-61.
Zaura E, Twetman S. Critical appraisal of oral probiotics. Br Dent J. 2019;226:593-600.
Rosier BT, De Jager M, Zaura E, Krom BP. Oral microbiome dynamics. J Dent Res. 2014;93:110-18.
Teughels W, Van Essche M, Sliepen I, Quirynen M. Probiotics and oral health care. Periodontol 2000. 2008;48:111-47.
Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, et al. Post-antibiotic gut mucosal microbiome reconstitution. Cell. 2018;174:1406-23.e16.
Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance. Cell. 2018;174:1388-405.e21.
FAO/WHO. Health and nutritional properties of probiotics. FAO Food Nutr Pap. 2006;85:1-50.
Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis. 2015;60(Suppl 2):S129-34.
Burton JP, Wescombe PA, Moore CJ, Chilcott CN, Tagg JR. Safety assessment of the oral probiotic Streptococcus salivarius K12. Appl Environ Microbiol. 2006;72:3050-3.
Haukioja A. Probiotics and oral adhesion. Oral Microbiol Immunol. 2010;25:361-6.
Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson Å, Sinkiewicz G. Decreased gingivitis by probiotic bacteria. J Clin Periodontol. 2006;33:745-52.
Keller MK, Twetman S. Acid production by probiotic lactobacilli. Oral Microbiol Immunol. 2012;27:356-61.
Jones SE, Versalovic J. Lactobacillus reuteri bioactive factors. Bioessays. 2009;31:203-13.
Lebeer S, Vanderleyden J, De Keersmaecker SCJ. Host interactions of probiotics. Nat Rev Microbiol. 2010;8:171-84.
Rickard AH, Palmer RJ Jr, Blehert DS, Campagna SR, Semmelhack MF, Egland PG, et al. Autoinducer 2: a concentration-dependent signal for mutualistic bacterial biofilm growth. Mol Microbiol. 2006;60:1446-56.
Wang BY, Kuramitsu HK. Interactions between oral bacteria. J Bacteriol. 2005;187:3472-9.
Groeger S, Meyle J. Epithelial barrier and periodontitis. Periodontol 2000. 2015;69:46-67.
Mennigen R, Bruewer M. Tight junction modulation by probiotics. Gut Microbes. 2009;1:1-8.
Van Dyke TE, Serhan CN. Resolution of inflammation. Nat Rev Immunol. 2013;13:349-61.
Sorsa T, Hernández M, Leppilahti J, Munjal S, Netuschil L, Mäntylä P. MMP-8 as a biomarker. J Clin Periodontol. 2016;43:545-55.
Brito F, de Barros CC, Cruz G, et al. Probiotics and bone metabolism. J Periodontal Res. 2013;48:249-58.
Donos N, Calciolari E, Brusselaers N, Goldoni M, Bostanci N, Belibasakis GN. Adjunctive host modulation in non-surgical periodontal therapy. Periodontol 2000. 2020;82:157-80.
Tekce M, Ince G, Gursoy H, Ipci SD, Cakar G, Kadir T, et al. Clinical and microbiological effects of probiotic lozenges. J Clin Periodontol. 2015;42:77-85.
Reid G, Burton J. Use of Lactobacillus reuteri in oral health. Benef Microbes. 2014;5:447-56.
Burton JP, Wescombe PA, Moore CJ, Chilcott CN, Tagg JR. Safety assessment of Streptococcus salivarius K12. Oral Microbiol Immunol. 2006;21:123-30.
Laleman I, Yilmaz E, Ozcelik O, Haytac C, Pauwels M, Herrero ER, et al. Streptococcal probiotics in periodontal therapy. J Clin Periodontol. 2015;42:1036-46.
Kang MS, Na HS, Oh JS. Coaggregation ability of Weissella cibaria isolates with Fusobacterium nucleatum. FEMS Microbiol Lett. 2005;253:323-29.
Kang MS, Lee DS, Kim M, Lee SA, Nam SH. Acidogenic potential of dental biofilms containing Weissella cibaria CMU. Int J Environ Res Public Health. 2021;18:4674.
Galofré M, Palao D, Vicario M, Nart J, Violant D. Probiotics in peri-implant mucositis. Clin Oral Implants Res. 2018;29:387-96.
Marcotte H, Lavoie MC. Recombinant probiotics in oral health. Microbiol Mol Biol Rev. 1998;62:295-317.
Referanslar
GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries, 1990–2016. Lancet. 2017;390:1211-59.
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366:1809-20.
Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038.
Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global prevalence of periodontal disease and lack of its surveillance. Sci World J. 2020;2020:2146160.
Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 2021;21:426-40.
Cardoso EM, Reis C, Manzanares-Céspedes MC. Chronic periodontitis and systemic diseases. Postgrad Med. 2018;130:98-104.
Cobb CM. Clinical significance of non-surgical periodontal therapy. J Clin Periodontol. 2002;29:6-16.
Aimetti M. Nonsurgical periodontal treatment. Int J Esthet Dent. 2014;9:251-67.
Haffajee AD, Teles RP, Socransky SS. Effect of periodontal therapy on subgingival microbiota. Periodontol 2000. 2006;42:219-58.
Jepsen K, Jepsen S. Antibiotics/antimicrobials in periodontal therapy. Periodontol 2000. 2016;71:82-112.
Rams TE, Degener JE, van Winkelhoff AJ. Antibiotic resistance in chronic periodontitis. J Periodontol. 2014;85:160-9.
Yoon MY, Yoon SS. Disruption of the gut ecosystem by antibiotics. Yonsei Med J. 2018;59:4-12.
FAO/WHO Working Group. Guidelines for the evaluation of probiotics in food. Report of a joint FAO/WHO working group. London, Ontario, Canada: Food and Agriculture Organization of the United Nations and World Health Organization; 2002.
Teughels W, Loozen G, Quirynen M. Probiotics and periodontal microbiota. J Clin Periodontol. 2011;38:159-77.
Seminario-Amez M, López-López J, Estrugo-Devesa A, Ayuso-Montero R, Jané-Salas E. Probiotics and oral health: a systematic review. Med Oral Patol Oral Cir Bucal. 2017;22:e282-8.
Pelekos G, Ho SN, Acharya A, Leung WK, McGrath C, Chatfield M, et al. Probiotics as adjuncts to non-surgical periodontal therapy: a systematic review and meta-analysis. J Clin Periodontol. 2019;46:1217-28.
Ho SN, Acharya A, Sahrmann P, Lewis K, Lau E, Paju S, et al. Probiotics as adjuncts to non-surgical periodontal therapy: systematic review and meta-analysis. J Evid Based Dent Pract. 2020;20:101397.
Ikram S, Hassan N, Raffat MA, Mirza S, Akram Z. Adjunctive probiotic therapy in chronic periodontitis: a systematic review and meta-analysis. J Investig Clin Dent. 2018;9:e12338.
Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, et al. The subgingival microbiome in health and periodontitis. ISME J. 2013;7:1016-25.
Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, et al. Distinct and complex bacterial profiles in human periodontitis and health. ISME J. 2012;6:1176-85.
Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontol 2000. 2020;83:14-25.
Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16:745-59.
Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25:134-44.
Hajishengallis G, Lamont RJ. Polymicrobial synergy and dysbiosis in inflammatory disease. Mol Oral Microbiol. 2012;27:409-19.
Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in periodontitis. Periodontol 2000. 2014;64:57-80.
Belkaid Y, Harrison OJ. Homeostatic immunity and the microbiota. Immunity. 2017;46:562-76.
Ince G, Gursoy H, Ipci SD, Cakar G, Emekli-Alturfan E, Yilmaz S. Clinical and microbiological effects of Lactobacillus reuteri in non-surgical periodontal therapy. J Periodontol. 2015;86:746-54.
Kuru BE, Laleman I, Yalnizoglu T, Kuru L, Teughels W. Influence of Bifidobacterium animalis probiotic on gingival health. J Periodontol. 2017;88:1115-23.
Invernici MM, Salvador SL, Silva PHF, Soares MSM, Casarin RCV, Palioto DB, et al. Effects of Bifidobacterium animalis subsp. lactis HN019 in chronic periodontitis. PLoS One. 2020;15:e0238425.
Flichy-Fernández AJ, Ata-Ali J, Alegre-Domingo T, Candel-Martí E, Ata-Ali F, Palacio J. Effect of Lactobacillus reuteri in peri-implant mucositis. J Periodontal Res. 2015;50:775-85.
Laleman I, Pauwels M, Quirynen M, Teughels W. Probiotics in peri-implantitis therapy. Clin Oral Implants Res. 2020;31:84-92.
Page RC, Kornman KS. The pathogenesis of human periodontitis. Periodontol 2000. 1997;14:9-11.
Hajishengallis G. Immune evasion strategies of Porphyromonas gingivalis. J Oral Biosci. 2011;53:233-40.
Lamont RJ, Hajishengallis G. Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol Med. 2015;21:172-83.
Marsh PD. Microbial ecology of dental plaque. Adv Dent Res. 1994;8:263-71.
Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000. 2006;42:180-218.
Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8:623-33.
Slots J. Periodontal pathogens. Periodontol 2000. 2002;28:56-71.
Holt SC, Ebersole JL. Porphyromonas gingivalis virulence factors. Periodontol 2000. 2005;38:22-38.
Fine DH, Schreiner H, Velusamy S. Aggregatibacter actinomycetemcomitans and aggressive periodontitis. Periodontol 2000. 2014;65:97-114.
Guo Y, Nguyen KA, Potempa J. Gingipains and periodontal disease. Periodontol 2000. 2010;54:79-99.
Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010;8:481-90.
Hajishengallis G, Lambris JD. Complement and dysbiosis in periodontal disease. Trends Immunol. 2011;32:310-18.
Heitz-Mayfield LJA, Lang NP. Surgical and non-surgical periodontal therapy. Periodontol 2000. 2013;62:68-86.
Bower RC. Furcation morphology relative to periodontal therapy. J Periodontol. 1979;50:366-74.
Bergström J. Smoking and periodontal disease. J Clin Periodontol. 2004;31:404-11.
Taylor GW, Borgnakke WS. Periodontal disease and diabetes. Periodontol 2000. 2008;44:127-53.
Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Berglundh T, et al. Treatment of stage I–III periodontitis. J Clin Periodontol. 2020;47(Suppl 22):4-60.
Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. ISAPP consensus statement on probiotics. Nat Rev Gastroenterol Hepatol. 2014;11:506-14.
Sanders ME. Probiotics: definition, sources, selection. Clin Infect Dis. 2008;46(Suppl 2):S58-61.
Zaura E, Twetman S. Critical appraisal of oral probiotics. Br Dent J. 2019;226:593-600.
Rosier BT, De Jager M, Zaura E, Krom BP. Oral microbiome dynamics. J Dent Res. 2014;93:110-18.
Teughels W, Van Essche M, Sliepen I, Quirynen M. Probiotics and oral health care. Periodontol 2000. 2008;48:111-47.
Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, et al. Post-antibiotic gut mucosal microbiome reconstitution. Cell. 2018;174:1406-23.e16.
Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance. Cell. 2018;174:1388-405.e21.
FAO/WHO. Health and nutritional properties of probiotics. FAO Food Nutr Pap. 2006;85:1-50.
Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis. 2015;60(Suppl 2):S129-34.
Burton JP, Wescombe PA, Moore CJ, Chilcott CN, Tagg JR. Safety assessment of the oral probiotic Streptococcus salivarius K12. Appl Environ Microbiol. 2006;72:3050-3.
Haukioja A. Probiotics and oral adhesion. Oral Microbiol Immunol. 2010;25:361-6.
Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson Å, Sinkiewicz G. Decreased gingivitis by probiotic bacteria. J Clin Periodontol. 2006;33:745-52.
Keller MK, Twetman S. Acid production by probiotic lactobacilli. Oral Microbiol Immunol. 2012;27:356-61.
Jones SE, Versalovic J. Lactobacillus reuteri bioactive factors. Bioessays. 2009;31:203-13.
Lebeer S, Vanderleyden J, De Keersmaecker SCJ. Host interactions of probiotics. Nat Rev Microbiol. 2010;8:171-84.
Rickard AH, Palmer RJ Jr, Blehert DS, Campagna SR, Semmelhack MF, Egland PG, et al. Autoinducer 2: a concentration-dependent signal for mutualistic bacterial biofilm growth. Mol Microbiol. 2006;60:1446-56.
Wang BY, Kuramitsu HK. Interactions between oral bacteria. J Bacteriol. 2005;187:3472-9.
Groeger S, Meyle J. Epithelial barrier and periodontitis. Periodontol 2000. 2015;69:46-67.
Mennigen R, Bruewer M. Tight junction modulation by probiotics. Gut Microbes. 2009;1:1-8.
Van Dyke TE, Serhan CN. Resolution of inflammation. Nat Rev Immunol. 2013;13:349-61.
Sorsa T, Hernández M, Leppilahti J, Munjal S, Netuschil L, Mäntylä P. MMP-8 as a biomarker. J Clin Periodontol. 2016;43:545-55.
Brito F, de Barros CC, Cruz G, et al. Probiotics and bone metabolism. J Periodontal Res. 2013;48:249-58.
Donos N, Calciolari E, Brusselaers N, Goldoni M, Bostanci N, Belibasakis GN. Adjunctive host modulation in non-surgical periodontal therapy. Periodontol 2000. 2020;82:157-80.
Tekce M, Ince G, Gursoy H, Ipci SD, Cakar G, Kadir T, et al. Clinical and microbiological effects of probiotic lozenges. J Clin Periodontol. 2015;42:77-85.
Reid G, Burton J. Use of Lactobacillus reuteri in oral health. Benef Microbes. 2014;5:447-56.
Burton JP, Wescombe PA, Moore CJ, Chilcott CN, Tagg JR. Safety assessment of Streptococcus salivarius K12. Oral Microbiol Immunol. 2006;21:123-30.
Laleman I, Yilmaz E, Ozcelik O, Haytac C, Pauwels M, Herrero ER, et al. Streptococcal probiotics in periodontal therapy. J Clin Periodontol. 2015;42:1036-46.
Kang MS, Na HS, Oh JS. Coaggregation ability of Weissella cibaria isolates with Fusobacterium nucleatum. FEMS Microbiol Lett. 2005;253:323-29.
Kang MS, Lee DS, Kim M, Lee SA, Nam SH. Acidogenic potential of dental biofilms containing Weissella cibaria CMU. Int J Environ Res Public Health. 2021;18:4674.
Galofré M, Palao D, Vicario M, Nart J, Violant D. Probiotics in peri-implant mucositis. Clin Oral Implants Res. 2018;29:387-96.
Marcotte H, Lavoie MC. Recombinant probiotics in oral health. Microbiol Mol Biol Rev. 1998;62:295-317.
