Manipulating the diseased oral microbiome: the power of probiotics and prebiotics

References

• Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512–16. doi: 10.1016/S0140-6736(03)12489-0
   PubMed Web of Science ®Google Scholar
• Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota - introducing the concept of prebiotics. J Nutr. 1995;125(6):1401–1412. doi: 10.1093/jn/125.6.1401
   PubMed Web of Science ®Google Scholar
• Fuller R. Probiotics in human medicine. Gut. 1991;32(4):439–42. doi: 10.1136/gut.32.4.439
   PubMed Web of Science ®Google Scholar
• Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol. 2010;7(9):503–14. doi: 10.1038/nrgastro.2010.117
   PubMed Web of Science ®Google Scholar
• Holzapfel WH, Haberer P, Snel J, et al. Overview of gut flora and probiotics. Int J Food Microbiol. 1998;41(2):85–101. doi: 10.1016/S0168-1605(98)00044-0
   PubMed Web of Science ®Google Scholar
• Isolauri E, Sutas Y, Kankaanpaa P, et al. Probiotics: effects on immunity. Am J Clin Nutr. 2001;73(2):444S–450S. doi: 10.1093/ajcn/73.2.444s
   PubMed Web of Science ®Google Scholar
• Majamaa H, Isolauri E. Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immun. 1997;99(2):179–185. doi: 10.1016/S0091-6749(97)70093-9
   PubMed Web of Science ®Google Scholar
• de Groot, PF, Belzer C, Aydin Ö, et al. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. PloS One. 2017;12(12):e0188475. doi: 10.1371/journal.pone.0188475
   PubMed Web of Science ®Google Scholar
• Long J, Cai Q, Steinwandel M, et al. Association of oral microbiome with type 2 diabetes risk. J Periodontal Res. 2017;52(3):636–43. doi: 10.1111/jre.12432
   PubMed Web of Science ®Google Scholar
• Brusca SB, Abramson SB, Scher JU. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol. 2014;26(1):101–7. doi: 10.1097/BOR.0000000000000008
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhang DY, Jia HJ, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895–905. doi: 10.1038/nm.3914
   PubMed Web of Science ®Google Scholar
• Mankia K, Cheng Z, Do T, et al. Prevalence of periodontal disease and periodontopathic bacteria in anti–cyclic citrullinated protein antibody–positive at-risk adults without arthritis. JAMA Netw Open. 2019;2(6):e195394–e. doi: 10.1001/jamanetworkopen.2019.5394
   PubMed Web of Science ®Google Scholar
• Zijian C, Thuy D, Kulveer M, et al. Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing rheumatoid arthritis. Ann Rheum Dis. 2021;80(2):162. doi: 10.1136/annrheumdis-2020-216972
   PubMed Web of Science ®Google Scholar
• El Kholy K, Genco RJ, Van Dyke TE. Oral infections and cardiovascular disease. Trends Endocrinol Metab. 2015;26(6):315–21. doi: 10.1016/j.tem.2015.03.001
   PubMed Web of Science ®Google Scholar
• Ordovas JM, Mooser V. Metagenomics: the role of the microbiome in cardiovascular diseases. Curr Opin Lipidol. 2006;17(2):157–161. doi: 10.1097/01.mol.0000217897.75068.ba
   PubMed Web of Science ®Google Scholar
• Pritchard AB, Crean S, Olsen I, et al. Periodontitis, microbiomes and their role in Alzheimer’s disease. Front Aging Neurosci query. 2017;9. doi: 10.3389/fnagi.2017.00336
   Google Scholar
• Shoemark DK, Allen SJ. The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer’s disease. J Alzheimers Dis. 2015;43(3):725–38. doi: 10.3233/JAD-141170
   PubMed Web of Science ®Google Scholar
• Singhrao SK, Olsen I. Assessing the role of Porphyromonas gingivalis in periodontitis to determine a causative relationship with Alzheimer’s disease. J Oral Microbiol. 2019;11(1):1563405. doi: 10.1080/20002297.2018.1563405
   PubMed Web of Science ®Google Scholar
• Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res. 1994;8(2):263–71. doi: 10.1177/08959374940080022001
   PubMedGoogle Scholar
• Devine DA, Marsh PD. Prospects for the development of probiotics and prebiotics for oral applications. J Oral Microbiol. 2009;1(1):1949. doi: 10.3402/jom.v1i0.1949
   Google Scholar
• Marsh PD, Head DA, Devine DA. Ecological approaches to oral biofilms: control without killing. Caries Res. 2015;49(Suppl. 1):46–54. doi: 10.1159/000377732
   PubMed Web of Science ®Google Scholar
• Marsh PD, Zaura E. Dental biofilm: ecological interactions in health and disease. J Clin Periodontal. 2017;44(S18):S12–S22. doi: 10.1111/jcpe.12679
   PubMedGoogle Scholar
• Kollath W. Nutrition and the tooth system; general review with special reference to vitamins. Deut Zahnaerztl Z. 1953;8(11):Suppl 7–16.
   Google Scholar
• Lilly DM, Stillwell RH. Probiotics - growth promoting factors produced by microorganisms. Science. 1965;147(3659):747±. doi: 10.1126/science.147.3659.747
   Web of Science ®Google Scholar
• Fuller R. Probiotics in man and animals. J Appl Bacteriol. 1989;66(5):365–378. doi: 10.1111/j.1365-2672.1989.tb05105.x
   PubMedGoogle Scholar
• Martín R, Langella P. Emerging health concepts in the probiotics field: streamlining the definitions. Front Microbiol. 2019;10(1047). doi: 10.3389/fmicb.2019.01047
   Google Scholar
• Gibson GR, Probert HM, Van Loo J, et al. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev. 2004;17(2):259–75. doi: 10.1079/NRR200479
   PubMed Web of Science ®Google Scholar
• Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: the international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491–502. doi: 10.1038/nrgastro.2017.75
   PubMed Web of Science ®Google Scholar
• Roberfroid M. Prebiotics: the concept revisited. J Nutr. 2007;137(3):830S–837S. doi: 10.1093/jn/137.3.830S
   PubMed Web of Science ®Google Scholar
• 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. doi: 10.1111/jre.12164
   PubMed Web of Science ®Google Scholar
• Näse L, Hatakka K, Savilahti E, et al. Effect of long–term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children. Caries Res. 2001;35(6):412–20. doi: 10.1159/000047484
   PubMed Web of Science ®Google Scholar
• Alkaya B, Laleman I, Keceli S, et al. Clinical effects of probiotics containing bacillus species on gingivitis: a pilot randomized controlled trial. J Periodontal Res. 2017;52(3):497–504. doi: 10.1111/jre.12415
   PubMed Web of Science ®Google Scholar
• Burton JP, Drummond BK, Chilcott CN, et al. Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial. J Med Microbiol. 2013;62(6):875–884. doi: 10.1099/jmm.0.056663-0
   PubMedGoogle Scholar
• Hedayati-Hajikand T, Lundberg U, Eldh C, et al. Effect of probiotic chewing tablets on early childhood caries–a randomized controlled trial. BMC Oral Health. 2015;15(1):112. doi: 10.1186/s12903-015-0096-5
   PubMedGoogle Scholar
• İ̇̇nce G, Gürsoy H, İ̇̇pçi ŞD, et al. 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. doi: 10.1902/jop.2015.140612
   PubMed Web of Science ®Google Scholar
• Jørgensen MR, Keller MK, Kragelund C, et al. Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: a randomized, double-blind, placebo-controlled, cross-over trial. Acta Odontol Scand. 2016;74(5):399–404. doi: 10.3109/00016357.2016.1169439
   PubMed Web of Science ®Google Scholar
• Rodriguez G, Ruiz B, Faleiros S, et al. Probiotic compared with standard milk for high-caries children: a cluster randomized trial. J Dent Res. 2016;95(4):402–7. doi: 10.1177/0022034515623935
   PubMed Web of Science ®Google Scholar
• Seidel CL, Gerlach RG, Weider M, et al. Influence of probiotics on the periodontium, the oral microbiota and the immune response during orthodontic treatment in adolescent and adult patients (ProMB trial): study protocol for a prospective, double-blind, controlled, randomized clinical trial. BMC Oral Health. 2022;22(1):148. doi: 10.1186/s12903-022-02180-8
   PubMed Web of Science ®Google Scholar
• Stecksén-Blicks C, Sjöström I, Twetman S. Effect of long-term consumption of milk supplemented with probiotic lactobacilli and fluoride on dental caries and general health in preschool children: a cluster-randomized study. Caries Res. 2009;43(5):374–81. doi: 10.1159/000235581
   PubMed Web of Science ®Google Scholar
• Tekce M, Ince G, Gursoy H, 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. doi: 10.1111/jcpe.12387
   PubMed Web of Science ®Google Scholar
• Twetman S, Derawi B, Keller M, et al. 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. doi: 10.1080/00016350802516170
   PubMed Web of Science ®Google Scholar
• Vivekananda M, Vandana K, Bhat K. Effect of the probiotic Lactobacilli reuteri (prodentis) in the management of periodontal disease: a preliminary randomized clinical trial. J Oral Microbiol. 2010;2(1):5344. doi: 10.3402/jom.v2i0.5344
   Google Scholar
• Sharma A, Rath GK, Chaudhary SP, et al. Lactobacillus brevis CD2 lozenges reduce radiation- and chemotherapy-induced mucositis in patients with head and neck cancer: a randomized double-blind placebo-controlled study. Eur J Cancer. 2012;48(6):875–81. doi: 10.1016/j.ejca.2011.06.010
   PubMed Web of Science ®Google Scholar
• Gruner D, Paris S, Schwendicke F. Probiotics for managing caries and periodontitis: systematic review and meta-analysis. J Dent. 2016;48:16–25. doi: 10.1016/j.jdent.2016.03.002
   PubMed Web of Science ®Google Scholar
• Ikram S, Hassan N, Raffat MA, et al. Systematic review and meta-analysis of double-blind, placebo-controlled, randomized clinical trials using probiotics in chronic periodontitis. J Investig Clin Dent. 2018;9(3):e12338. doi: 10.1111/jicd.12338
   PubMed Web of Science ®Google Scholar
• Mundula T, Ricci F, Barbetta B, et al. Effect of probiotics on oral candidiasis: a systematic review and meta-analysis. Nutrients. 2019;11(10):2449. doi: 10.3390/nu11102449
   PubMed Web of Science ®Google Scholar
• Seminario-Amez M, Lopez-Lopez J, Estrugo-Devesa A, et al. Probiotics and oral health: a systematic review. Med Oral Patol Oral Cir Bucal. 2017;22(3):e282–e8. doi: 10.4317/medoral.21494
   PubMed Web of Science ®Google Scholar
• Cagetti MG, Mastroberardino S, Milia E, et al. The use of probiotic strains in caries prevention: a systematic review. Nutrients. 2013;5(7):2530–50. doi: 10.3390/nu5072530
   PubMed Web of Science ®Google Scholar
• Martin-Cabezas R, Davideau J-L, Tenenbaum H, et al. Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of chronic periodontitis: a systematic review and meta-analysis. J Clin Periodontol. 2016;43(6):520–30. doi: 10.1111/jcpe.12545
   PubMed Web of Science ®Google Scholar
• Liu J, Liu Z, Huang J, et al. Effect of probiotics on gingival inflammation and oral microbiota: a meta-analysis. Oral Dis. 2022;28(4):1058–67. doi: 10.1111/odi.13861
   PubMed Web of Science ®Google Scholar
• Azad MAK, Sarker M, Li T, et al. Probiotic species in the modulation of gut microbiota: an overview. Biomed Res Int. 2018;2018:9478630–. doi: 10.1155/2018/9478630
   PubMed Web of Science ®Google Scholar
• Srivastava S, Saha S, Kumari M, et al. Effect of probiotic curd on salivary pH and Streptococcus mutans: a double blind parallel randomized controlled trial. J Clin Diagn Res. 2016;10(2):ZC13–6. doi: 10.7860/JCDR/2016/15530.7178
   PubMedGoogle Scholar
• Saha S, Tomaro-Duchesneau C, Rodes L, et al. Investigation of probiotic bacteria as dental caries and periodontal disease biotherapeutics. Benef Microbes. 2014;5(4):447–60. doi: 10.3920/BM2014.0011
   PubMed Web of Science ®Google Scholar
• Morales A, Carvajal P, Silva N, et al. Clinical effects of Lactobacillus rhamnosus in non-surgical treatment of chronic periodontitis: a randomized placebo-controlled trial with 1-year follow-up. J Periodontol. 2016;87(8):944–52. doi: 10.1902/jop.2016.150665
   PubMed Web of Science ®Google Scholar
• Teughels W, Durukan A, Ozcelik O, et al. 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. doi: 10.1111/jcpe.12155
   PubMed Web of Science ®Google Scholar
• Ikram S, Hassan N, Baig S, et al. Clinical efficacy of probiotics as an adjunct to scaling and root planning in the treatment of chronic periodontitis. Ann Abbasi Shaheed H. 2019;24(1):31–37. doi: 10.58397/ashkmdc.v24i1.24
   Google Scholar
• Kim Y-J, Lee S-H. Inhibitory effect of Lactococcus lactis HY 449 on cariogenic biofilm. J Microbiol Biotechnol. 2016;26(11):1829–35. doi: 10.4014/jmb.1604.04008
   PubMed Web of Science ®Google Scholar
• Kuru BE, Laleman I, Yalnizoglu T, et al. The influence of a Bifidobacterium animalis probiotic on gingival health: a randomized controlled clinical trial. J Periodontol. 2017;88(11):1115–23. doi: 10.1902/jop.2017.170213
   PubMed Web of Science ®Google Scholar
• Lee K, Walker AR, Chakraborty B, et al. Novel probiotic mechanisms of the oral bacterium Streptococcus sp. A12 as explored with functional genomics. Appl Environ Microbiol. 2019;85(21). doi: 10.1128/AEM.01335-19
   Web of Science ®Google Scholar
• Holmes ZC, Villa MM, Durand HK, et al. Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake. Microbiome. 2022;10(1):114. doi: 10.1186/s40168-022-01307-x
   PubMed Web of Science ®Google Scholar
• Ismail HM, Spall M, Evans-Molina C, et al. Evaluating the effect of prebiotics on the gut microbiome profile and β cell function in youth with newly diagnosed type 1 diabetes: protocol of a pilot randomized controlled trial. Pilot And Feasibility Stud. 2023;9(1):150. doi: 10.1186/s40814-023-01373-4
   PubMedGoogle Scholar
• Ni Lochlainn M, Nessa A, Sheedy A, et al. The PROMOTe study: targeting the gut microbiome with prebiotics to overcome age-related anabolic resistance: protocol for a double-blinded, randomised, placebo-controlled trial. BMC Geriatr. 2021;21(1):407. doi: 10.1186/s12877-021-02301-y
   PubMed Web of Science ®Google Scholar
• Slomka V, Hernandez‐Sanabria E, Herrero ER, et al. Nutritional stimulation of commensal oral bacteria suppresses pathogens: the prebiotic concept. J Clin Periodontol. 2017;44(4):344–52. doi: 10.1111/jcpe.12700
   PubMed Web of Science ®Google Scholar
• Kolenbrander PE, Andersen RN. Inhibition of coaggregation between Fusobacterium nucleatum and Porphyromonas (Bacteroides) gingivalis by lactose and related sugars. Infect Immun. 1989;57(10):3204–9. doi: 10.1128/iai.57.10.3204-3209.1989
   PubMed Web of Science ®Google Scholar
• Qu X, Wu Z, Pang B, et al. From nitrate to nitric oxide: the role of salivary glands and oral bacteria. J Dental Res. 2016;95(13):1452–1456. doi: 10.1177/0022034516673019
   PubMed Web of Science ®Google Scholar
• Rosier BT, Moya-Gonzalvez EM, Corell-Escuin P, et al. Isolation and characterization of nitrate-reducing bacteria as potential probiotics for oral and systemic health. Front Microbiol. 2020;11:555465. doi: 10.3389/fmicb.2020.555465
   PubMed Web of Science ®Google Scholar
• Morou-Bermúdez E, Torres-Colón J, Bermúdez N, et al. Pathways linking oral bacteria, nitric oxide metabolism, and health. J Dent Res. 2022;101(6):623–31. doi: 10.1177/00220345211064571
   PubMed Web of Science ®Google Scholar
• Rosier B, Buetas E, Moya-Gonzalvez E, et al. Nitrate as a potential prebiotic for the oral microbiome. Sci Rep. 2020;10(1):1–15. doi: 10.1038/s41598-020-69931-x
   PubMed Web of Science ®Google Scholar
• Konde S, Ravindran S, Agarwal M, et al. Prebiotics-a primeval measure to combat dental caries: a short-term clinical study. Int J Clin Pediatr Dent. 2022;15(Suppl 2):S234–s8. doi: 10.5005/jp-journals-10005-2165
   PubMedGoogle Scholar
• Nunpan H, Suwannachart C, Wayakanon K. Effect of prebiotics-enhanced probiotics on the growth of Streptococcus mutans. Int J Microbiol. 2019;2019:1–7. doi: 10.1155/2019/4623807
   Web of Science ®Google Scholar
• James SL, Abate D, Abate KH, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2018;392(10159):1789–858. doi: 10.1016/S0140-6736(18)32279-7
   PubMed Web of Science ®Google Scholar
• Hujoel PP, Lingström P. Nutrition, dental caries and periodontal disease: a narrative review. J Clin Periodontol. 2017;44(S18):S79–S84. doi: 10.1111/jcpe.12672
   PubMedGoogle Scholar
• Moye ZD, Zeng L, Burne RA. Fueling the caries process: carbohydrate metabolism and gene regulation by Streptococcus mutans. J Oral Microbiol. 2014;6(1):24878. doi: 10.3402/jom.v6.24878
   Google Scholar
• Lee S-H, Kim Y-J. A comparative study of the effect of probiotics on cariogenic biofilm model for preventing dental caries. Arch Microbiol. 2014;196(8):601–9. doi: 10.1007/s00203-014-0998-7
   PubMed Web of Science ®Google Scholar
• Ren Z, Chen L, Li J, et al. Inhibition of Streptococcus mutans polysaccharide synthesis by molecules targeting glycosyltransferase activity. J Oral Microbiol. 2016;8(1):31095–. doi: 10.3402/jom.v8.31095
   PubMed Web of Science ®Google Scholar
• Çaglar E, Sandalli N, Twetman S, et al. Effect of yogurt with Bifidobacterium DN-173 010 on salivary mutans streptococci and lactobacilli in young adults. Acta Odontol Scand. 2005;63(6):317–20. doi: 10.1080/00016350510020070
   PubMed Web of Science ®Google Scholar
• Cildir SK, Germec D, Sandalli N, et al. Reduction of salivary mutans streptococci in orthodontic patients during daily consumption of yoghurt containing probiotic bacteria. Eur J Orthod. 2009;31(4):407–11. doi: 10.1093/ejo/cjn108
   PubMed Web of Science ®Google Scholar
• Singh R, Damle SG, Chawla A. Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifidobacterium lactis Bb12 and Lactobacillus acidophilus La5. Acta Odontol Scand. 2011;69(6):389–94. doi: 10.3109/00016357.2011.572289
   PubMed Web of Science ®Google Scholar
• Nagarajappa R, Daryani H, Sharda AJ, et al. Effect of chocobar ice cream containing bifidobacterium on salivary Streptococcus mutans and lactobacilli: a randomised controlled trial. Oral Health Prev Dent. 2015;13(3):213–8. doi: 10.3290/j.ohpd.a32673
   PubMed Web of Science ®Google Scholar
• Haukioja A, Yli‐Knuuttila H, Loimaranta V, et al. Oral adhesion and survival of probiotic and other lactobacilli and bifidobacteria in vitro. Oral Microbiol Immun. 2006;21(5):326–32. doi: 10.1111/j.1399-302X.2006.00299.x
   PubMedGoogle Scholar
• Lin C-W, Chen Y-T, Ho H-H, et al. Lozenges with probiotic strains enhance oral immune response and health. Oral Dis. 2022;28(6):1723–32. doi: 10.1111/odi.13854
   PubMed Web of Science ®Google Scholar
• Ma D, Forsythe P, Bienenstock J. Live Lactobacillus reuteri is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infect Immun. 2004;72(9):5308–14. doi: 10.1128/IAI.72.9.5308-5314.2004
   PubMed Web of Science ®Google Scholar
• Messora MR, Pereira LJ, Foureaux R, et al. Favourable effects of Bacillus subtilis and Bacillus licheniformis on experimental periodontitis in rats. Arch Oral Biol. 2016;66:108–119. doi: 10.1016/j.archoralbio.2016.02.014
   PubMed Web of Science ®Google Scholar
• Schaefer L, Auchtung TA, Hermans KE, et al. The antimicrobial compound reuterin (3-hydroxypropionaldehyde) induces oxidative stress via interaction with thiol groups. Microbiology. 2010;156(6):1589–99. doi: 10.1099/mic.0.035642-0
   PubMedGoogle Scholar
• Fuller R, Gibson GR. Modification of the intestinal microflora using probiotics and prebiotics. Scand J Gastroenterol. 1997;32(sup222):28–31. doi: 10.1080/00365521.1997.11720714
   PubMed Web of Science ®Google Scholar
• Jamali Z, Aminabadi NA, Samiei M, et al. Impact of chlorhexidine pretreatment followed by Probiotic Streptococcus salivarius strain K12 on halitosis in children: a randomised controlled clinical trial. Oral Health Prev Dent. 2016;14(4):305–13. doi: 10.3290/j.ohpd.a36521
   PubMed Web of Science ®Google Scholar
• Laleman I, Yilmaz E, Ozcelik O, et al. The effect of a streptococci containing probiotic in periodontal therapy: a randomized controlled trial. J Clin Periodontol. 2015;42(11):1032–41. doi: 10.1111/jcpe.12464
   PubMed Web of Science ®Google Scholar
• Hillman J, McDonell E, Cramm T, et al. A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries. J Appl Microbiol. 2009;107(5):1551–8. doi: 10.1111/j.1365-2672.2009.04333.x
   PubMed Web of Science ®Google Scholar
• Hillman JD, Andrews SW, Dzuback AL. Acetoin production by wild-type strains and a lactate dehydrogenase-deficient mutant of Streptococcus mutans. Infect Immun. 1987;55(6):1399–402. doi: 10.1128/iai.55.6.1399-1402.1987
   PubMed Web of Science ®Google Scholar
• Fitzgerald RJ, Adams BO, Sandham HJ, et al. Cariogenicity of a lactate dehydrogenase-deficient mutant of Streptococcus mutans serotype c in gnotobiotic rats. Infect Immun. 1989;57(3):823–6. doi: 10.1128/iai.57.3.823-826.1989
   PubMed Web of Science ®Google Scholar
• Gupta S, Marwah N. ‘Use a thorn to draw thorn’ replacement therapy for prevention of dental caries. Int J Clin Pediatr Dent. 2010;3(3):125–137. doi: 10.5005/jp-journals-10005-1068
   PubMedGoogle Scholar
• Hillman JD. Lactate dehydrogenase mutants of Streptococcus mutans: isolation and preliminary characterization. Infect Immun. 1978;21(1):206–12. doi: 10.1128/iai.21.1.206-212.1978
   PubMed Web of Science ®Google Scholar
• Hillman JD. Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie Van Leeuwenhoek. 2002;82(1–4):361–366. doi: 10.1023/A:1020695902160
   PubMed Web of Science ®Google Scholar
• Pan W, Mao T, Xu QA, et al. A new gcrR-deficient Streptococcus mutans mutant for replacement therapy of dental caries. Sci World J. 2013;2013:460202. doi: 10.1155/2013/460202
   Google Scholar
• Sun J-H, Xu Q-A, Fan M-W. A new strategy for the replacement therapy of dental caries. Med Hypotheses. 2009;73(6):1063–4. doi: 10.1016/j.mehy.2009.04.045
   PubMed Web of Science ®Google Scholar
• Tanzer J, Freedman ML, Fitzgerald RJ. Diminished virulence of glucan synthesis-defective mutants of Streptococcus mutans. Infect Immun. 1974;10(1):197–203. doi: 10.1128/iai.10.1.197-203.1974
   PubMed Web of Science ®Google Scholar
• Tanzer JM, Freedman ML. Genetic alterations of Streptococcus mutans’ virulence. Adv Exp Med Biol. 1978;107:661–672.
   PubMedGoogle Scholar
• Hillman J, Yaphe B, Johnson K. Colonization of the human oral cavity by a strain of Streptococcus mutans. J Dent Res. 1985;64(11):1272–4. doi: 10.1177/00220345850640110301
   PubMed Web of Science ®Google Scholar
• Wang Y, Dong J, Wang J, et al. Assessing the drug resistance profiles of oral probiotic lozenges. J Oral Microbiol. 2022;14(1):2019992. doi: 10.1080/20002297.2021.2019992
   PubMed Web of Science ®Google Scholar
• Spielberg S. Jurassic park. USA: Universal Pictures; 1993.
   Google Scholar
• Galbraith S, Marschner IC, Marschner IC. Guidelines for the design of clinical trials with longitudinal outcomes. Control Clin Trials. 2002;23(3):257–273. doi: 10.1016/S0197-2456(02)00205-2
   PubMedGoogle Scholar
• Witte MB, Thornton FJ, Tantry U, et al. L-Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways. Metab Clin Exp. 2002;51(10):1269–73. doi: 10.1053/meta.2002.35185
   PubMed Web of Science ®Google Scholar
• Suchner U, Heyland D, Peter K. Immune-modulatory actions of arginine in the critically ill. Br J Nutr. 2002;87(S1):S121–S32. doi: 10.1079/BJN2001465
   PubMedGoogle Scholar
• Kang K, Shu X-L, Zhong J-X, et al. Effect of L-arginine on immune function: a meta-analysis. Asia Pac J Clin Nutr. 2014;23(3):351.
   PubMed Web of Science ®Google Scholar
• Wu G, Meininger CJ. Arginine nutrition and cardiovascular function. J Nutr. 2000;130(11):2626–9. doi: 10.1093/jn/130.11.2626
   PubMed Web of Science ®Google Scholar
• Kraivaphan P, Amornchat C, Triratana T, et al. Two-year caries clinical study of the efficacy of novel dentifrices containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm fluoride. Caries Res. 2013;47(6):582–90. doi: 10.1159/000353183
   PubMed Web of Science ®Google Scholar
• Tada A, Nakayama-Imaohji H, Yamasaki H, et al. Cleansing effect of acidic L-arginine on human oral biofilm. BMC Oral Health. 2016;16(1):40. doi: 10.1186/s12903-016-0194-z
   PubMedGoogle Scholar
• Wolff M, Schenkel A. The anticaries efficacy of a 1.5% arginine and fluoride toothpaste. Adv Dent Res. 2018;29(1):93–7. doi: 10.1177/0022034517735298
   PubMedGoogle Scholar
• Liu Y-L, Nascimento M, Burne RA. Progress toward understanding the contribution of alkali generation in dental biofilms to inhibition of dental caries. Int J Oral Sci. 2012;4(3):135–40. doi: 10.1038/ijos.2012.54
   PubMed Web of Science ®Google Scholar
• Huang X, Schulte RM, Burne RA, et al. Characterization of the arginolytic microflora provides insights into pH homeostasis in human oral biofilms. Caries Res. 2015;49(2):165–76. doi: 10.1159/000365296
   PubMed Web of Science ®Google Scholar
• Nascimento MM, Burne RA. Caries prevention by arginine metabolism in oral biofilms: translating science into clinical success. Curr Oral Health Rep. 2014;1(1):79–85. doi: 10.1007/s40496-013-0007-2
   Google Scholar
• Griswold AR, Chen Y-Y, Burne RA. Analysis of an agmatine deiminase gene cluster in Streptococcus mutans UA159. J Bacteriol. 2004;186(6):1902–1904. doi: 10.1128/JB.186.6.1902-1904.2004
   PubMed Web of Science ®Google Scholar
• Griswold AR, Nascimento MM, Burne RA. Distribution, regulation and role of the agmatine deiminase system in mutans streptococci. Oral Microbiol Immunol. 2009;24(1):79–82. doi: 10.1111/j.1399-302X.2008.00459.x
   PubMedGoogle Scholar
• Nascimento M, Gordan V, Garvan C, et al. Correlations of oral bacterial arginine and urea catabolism with caries experience. Oral Microbiol Immun. 2009;24(2):89–95. doi: 10.1111/j.1399-302X.2008.00477.x
   PubMedGoogle Scholar
• Nascimento MM, Browngardt C, Xiaohui X, et al. The effect of arginine on oral biofilm communities. Mol Oral Microbiol. 2014;29(1):45–54. doi: 10.1111/omi.12044
   PubMed Web of Science ®Google Scholar
• Nascimento M, Alvarez A, Huang X, et al. Metabolic profile of supragingival plaque exposed to arginine and fluoride. J Dent Res. 2019;98(11):1245–52. doi: 10.1177/0022034519869906
   PubMed Web of Science ®Google Scholar
• Zheng X, He J, Wang L, et al. Ecological effect of arginine on oral microbiota. Sci Rep. 2017;7(1):1–10. doi: 10.1038/s41598-017-07042-w
   PubMedGoogle Scholar
• Koopman JE, Hoogenkamp MA, Buijs MJ, et al. Changes in the oral ecosystem induced by the use of 8% arginine toothpaste. Arch Oral Biol. 2017;73:79–87. doi: 10.1016/j.archoralbio.2016.09.008
   PubMed Web of Science ®Google Scholar
• Kuriki N, Asahi Y, Sotozono M, et al. Next-generation sequencing for determining the effect of arginine on human dental biofilms using an in situ model. Pharmacy. 2021;9(1):18. doi: 10.3390/pharmacy9010018
   Web of Science ®Google Scholar
• Sessler DI, Alman BA, Treggiari MM, et al. Pro-con debate: interdisciplinary perspectives on industry-sponsored research. J Arthroplasty. 2023;38(6):986–991. doi: 10.1016/j.arth.2023.02.018
   PubMed Web of Science ®Google Scholar
• Goldman AS, Yee R, Holmgren CJ, et al. Global affordability of fluoride toothpaste. Global Health. 2008;4(1):7. doi: 10.1186/1744-8603-4-7
   PubMedGoogle Scholar
• O Mullane D, Baez R, Jones S, et al. Fluoride and oral health. Community Dent Health. 2016;33(2):69–99.
   PubMed Web of Science ®Google Scholar
• Whelton H, Spencer A, Do L, et al. Fluoride revolution and dental caries: evolution of policies for global use. J Dent Res. 2019;98(8):837–46. doi: 10.1177/0022034519843495
   PubMed Web of Science ®Google Scholar
• Marquis RE. Antimicrobial actions of fluoride for oral bacteria. Can J Microbiol. 1995;41(11):955–964. doi: 10.1139/m95-133
   PubMed Web of Science ®Google Scholar
• Belli W, Buckley D, Marquis R. Weak acid effects and fluoride inhibition of glycolysis by Streptococcus mutans GS-5. Can J Microbiol. 1995;41(9):785–791. doi: 10.1139/m95-108
   PubMed Web of Science ®Google Scholar
• Tenuta L, Cerezetti R, Del Bel Cury A, et al. Fluoride release from CaF2 and enamel demineralization. Int Jou of Medi Res & Hea Sci. 2020;9(5):20–32. doi: 10.1177/154405910808701105
   Google Scholar
• Lynch R, Navada R, Walia R. Low‐levels of fluoride in plaque and saliva and their effects on the demineralisation and remineralisation of enamel; role of fluoride toothpastes. Int Dent J. 2004;54(S5):304–309. doi: 10.1111/j.1875-595X.2004.tb00003.x
   PubMedGoogle Scholar
• Koopman JE, van der Kaaij NC, Buijs MJ, et al. The effect of fixed orthodontic appliances and fluoride mouthwash on the oral microbiome of adolescents–a randomized controlled clinical trial. PloS One. 2015;10(9):e0137318. doi: 10.1371/journal.pone.0137318
   PubMed Web of Science ®Google Scholar
• Reilly C, Goettl M, Steinmetz M, et al. Short‐term effects of povidone iodine and sodium fluoride therapy on plaque levels and microbiome diversity. Oral Dis. 2016;22(2):155–61. doi: 10.1111/odi.12407
   PubMed Web of Science ®Google Scholar
• López-López A, Mira A. Shifts in composition and activity of oral biofilms after fluoride exposure. Microbial Ecol. 2020;80(3):1–10. doi: 10.1007/s00248-020-01531-8
   PubMed Web of Science ®Google Scholar
• Carda-Diéguez M, Moazzez R, Mira A. Functional changes in the oral microbiome after use of fluoride and arginine containing dentifrices: a metagenomic and metatranscriptomic study. Microbiome. 2022;10(1):1–20. doi: 10.1186/s40168-022-01338-4
   PubMed Web of Science ®Google Scholar
• Zheng X, Cheng X, Wang L, et al. Combinatorial effects of arginine and fluoride on oral bacteria. J Dent Res. 2015;94(2):344–53. doi: 10.1177/0022034514561259
   PubMed Web of Science ®Google Scholar
• Bijle MNA, Ekambaram M, Lo EC, et al. The combined antimicrobial effect of arginine and fluoride toothpaste. Sci Rep. 2019;9(1):1–10. doi: 10.1038/s41598-019-44612-6
   PubMedGoogle Scholar
• Santarpia R, Lavender S, Gittins E, et al. A 12-week clinical study assessing the clinical effects on plaque metabolism of a dentifrice containing 1.5% arginine, an insoluble calcium compound and 1,450 ppm fluoride. Am J Dent. 2014;27(2):100–105.
   PubMed Web of Science ®Google Scholar
• Wolff M, Corby P, Klaczany G, et al. In vivo effects of a new dentifrice containing 1.5% arginine and 1450 ppm fluoride on plaque metabolism. J Clin Dent. 2013;24 Spec no A:A45.
   PubMedGoogle Scholar
• Yin W, Hu D, Li X, et al. The anti-caries efficacy of a dentifrice containing 1.5% arginine and 1450 ppm fluoride as sodium monofluorophosphate assessed using quantitative light-induced fluorescence (QLF). J Dent. 2013;41:S22–S8. doi: 10.1016/j.jdent.2010.04.004
   PubMed Web of Science ®Google Scholar
• Li X, Zhong Y, Jiang X, et al. Randomized clinical trial of the efficacy of dentifrices containing 1.5% arginine, an insoluble calcium compound and 1450 ppm fluoride over two years. J Clin Dent. 2015;26(1):7–12.
   PubMedGoogle Scholar
• Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3(1):17038. doi: 10.1038/nrdp.2017.38
   PubMed Web of Science ®Google Scholar
• Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16(12):745–59. doi: 10.1038/s41579-018-0089-x
   PubMed Web of Science ®Google Scholar
• Shetty S, Srigiri SK, Sheikh KH. A comparative clinical, microbiological and biochemical evaluation of guided periodontal pocket recolonisation (GPR) using synbiotics as an adjunct to scaling and root planing in patients with chronic periodontitis: a Pilot project. 2020.
   Google Scholar
• Hajishengallis G. The inflammophilic character of the periodontitis-associated microbiota. Mol Oral Microbiol. 2014;29(6):248–57. doi: 10.1111/omi.12065
   PubMed Web of Science ®Google Scholar
• Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809–20. doi: 10.1016/S0140-6736(05)67728-8
   PubMed Web of Science ®Google Scholar
• Devine DA, Marsh PD, Meade J. Modulation of host responses by oral commensal bacteria. J Oral Microbiol. 2015;7(1):26941. doi: 10.3402/jom.v7.26941
   PubMed Web of Science ®Google Scholar
• Myers S, Do T, Meade JL, et al. Immunomodulatory streptococci that inhibit CXCL8 secretion and NFκB activation are common members of the oral microbiota. J Med Microbiol. 2021;70(3). doi: 10.1099/jmm.0.001329
   PubMed Web of Science ®Google Scholar
• Cosseau C, Devine DA, Dullaghan E, et al. The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun. 2008;76(9):4163–75. doi: 10.1128/IAI.00188-08
   PubMed Web of Science ®Google Scholar
• Gheisary Z, Mahmood R, Harri Shivanantham A, et al. The clinical, microbiological, and immunological effects of probiotic supplementation on prevention and treatment of periodontal diseases: a systematic review and meta-analysis. Nutrients. 2022;14(5):1036. doi: 10.3390/nu14051036
   PubMed Web of Science ®Google Scholar
• Lima LM, Motisuki C, Madalena Palomari Spolidorio D, et al. In vitro evaluation of probiotics microorganisms adhesion to an artificial caries model. Eur J Clin Nutr. 2005;59(7):884–6. doi: 10.1038/sj.ejcn.1602158
   PubMed Web of Science ®Google Scholar
• Wu C-Y, He S-J, Mar K, et al. Inhibition of Streptococcus mutans by a commercial yogurt drink. J Dent Sci. 2019;14(2):198–205. doi: 10.1016/j.jds.2018.11.007
   PubMed Web of Science ®Google Scholar
• Sato T, Nakazawa F. Coaggregation between Prevotella oris and Porphyromonas gingivalis. Journal Of Microbiology, Immunol Infect. 2014;47(3):182–186. doi: 10.1016/j.jmii.2012.09.005
   PubMedGoogle Scholar
• Ito R, Ishihara K, Shoji M, et al. Hemagglutinin/Adhesin domains of Porphyromonas gingivalis play key roles in coaggregation with Treponema denticola. FEMS Immunol Med Microbiol. 2010;60(3):251–60. doi: 10.1111/j.1574-695X.2010.00737.x
   PubMedGoogle Scholar
• Rickard AH, Gilbert P, High NJ, et al. Bacterial coaggregation: an integral process in the development of multi-species biofilms. Trends Microbiol. 2003;11(2):94–100. doi: 10.1016/S0966-842X(02)00034-3
   PubMed Web of Science ®Google Scholar
• Hezel M, Weitzberg E. The oral microbiome and nitric oxide homoeostasis. Oral Dis. 2015;21(1):7–16. doi: 10.1111/odi.12157
   PubMed Web of Science ®Google Scholar
• Sánchez GA, Miozza VA, Delgado A, et al. Total salivary nitrates and nitrites in oral health and periodontal disease. Nitric Oxide. 2014;36:31–5. doi: 10.1016/j.niox.2013.10.012
   PubMed Web of Science ®Google Scholar
• Rosier BT, Takahashi N, Zaura E, et al. The importance of nitrate reduction for oral health. J Dent Res. 2022;101(8):887–97. doi: 10.1177/00220345221080982
   PubMed Web of Science ®Google Scholar
• Schreiber F, Stief P, Gieseke A, et al. Denitrification in human dental plaque. BMC Biol. 2010;8(1):24. doi: 10.1186/1741-7007-8-24
   PubMedGoogle Scholar
• Wang Y, Huang X, He F. Mechanism and role of nitric oxide signaling in periodontitis. Exp Ther Med. 2019;18(5):3929–35. doi: 10.3892/etm.2019.8044
   PubMed Web of Science ®Google Scholar
• Alamri MM, Williams B, Le Guennec A, et al. Metabolomics analysis in saliva from periodontally healthy, gingivitis and periodontitis patients. J Periodont Res. 2023;58(6):1272–80. doi: 10.1111/jre.13183
   PubMed Web of Science ®Google Scholar
• Citterio F, Romano F, Meoni G, et al. Changes in the salivary metabolic profile of generalized periodontitis patients after non-surgical periodontal therapy: a metabolomic analysis using nuclear magnetic resonance spectroscopy. J Clin Med. 2020;9(12):3977. doi: 10.3390/jcm9123977
   PubMed Web of Science ®Google Scholar
• Rzeznik M, Triba MN, Levy P, et al. Identification of a discriminative metabolomic fingerprint of potential clinical relevance in saliva of patients with periodontitis using 1H nuclear magnetic resonance (NMR) spectroscopy. PloS One. 2017;12(8):e0182767. doi: 10.1371/journal.pone.0182767
   PubMed Web of Science ®Google Scholar
• Wei Y, Shi M, Nie Y, et al. Integrated analysis of the salivary microbiome and metabolome in chronic and aggressive periodontitis: a pilot study. Front Microbiol. 2022;13:959416. doi: 10.3389/fmicb.2022.959416
   PubMed Web of Science ®Google Scholar
• Li K, Wang J, Du N, et al. Salivary microbiome and metabolome analysis of severe early childhood caries. BMC Oral Health. 2023;23(1):30. doi: 10.1186/s12903-023-02722-8
   PubMed Web of Science ®Google Scholar
• Musalem-Dominguez O, Montiel-Company JM, Ausina-Márquez V, et al. Salivary metabolomic profile associated with cariogenic risk in children. J Dent. 2023;136:104645. doi: 10.1016/j.jdent.2023.104645
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhang Y, Pan T, et al. Metabolic differences of the oral microbiome related to dental caries - A pilot study. Arch Oral Biol. 2022;141:105471. doi: 10.1016/j.archoralbio.2022.105471
   PubMed Web of Science ®Google Scholar
• Takahashi N. Oral microbiome metabolism: from “who are they?” to “what are they doing?”. J Dent Res. 2015;94(12):1628–37. doi: 10.1177/0022034515606045
   PubMed Web of Science ®Google Scholar
• Takahashi N, Yamada T. Glucose and lactate metabolism by Actinomyces naeslundii. Critical Rev Oral Biol Med. 1999;10(4):487–503. doi: 10.1177/10454411990100040501
   PubMedGoogle Scholar
• Takahashi N, Washio J, Mayanagi G. Metabolomic approach to oral biofilm characterization—A future direction of biofilm research. J Oral Biosci. 2012;54(3):138–43. doi: 10.1016/j.job.2012.02.005
   Google Scholar
• Heimisdottir LH, Lin BM, Cho H, et al. Metabolomics insights in early childhood caries. J Dent Res. 2021;100(6):615–22. doi: 10.1177/0022034520982963
   PubMed Web of Science ®Google Scholar
• Wen ZT, Liao S, Bitoun JP, et al. Streptococcus mutans displays altered stress responses while enhancing biofilm formation by Lactobacillus casei in mixed-species consortium. Front Cell Infect Microbiol. 2017;7:524. doi: 10.3389/fcimb.2017.00524
   PubMed Web of Science ®Google Scholar
• Zhang Q, Li J, Lu W, et al. Multi-omics reveals the inhibition of Lactiplantibacillus plantarum CCFM8724 in Streptococcus mutans-Candida albicans mixed-species biofilms. Microorganisms. 2021;9(11):2368. doi: 10.3390/microorganisms9112368
   PubMed Web of Science ®Google Scholar
• Belda-Ferre P, Williamson J, Simón-Soro Á, et al. The human oral metaproteome reveals potential biomarkers for caries disease. Proteomics. 2015;15(20):3497–3507. doi: 10.1002/pmic.201400600
   PubMed Web of Science ®Google Scholar
• Seibold GM, Breitinger KJ, Kempkes R, et al. The glgB-encoded glycogen branching enzyme is essential for glycogen accumulation in Corynebacterium glutamicum. Microbiology. 2011;157(11):3243–51. doi: 10.1099/mic.0.051565-0
   PubMedGoogle Scholar
• Yazdani R, Albujeer AN, Rahnama E, et al. Effect of xylitol on salivary Streptococcus mutans: a systematic review and meta-analysis. J Contemp Med Sci. 2019;5(2):64–70. doi: 10.22317/jcms.v5i2.582
   Web of Science ®Google Scholar
• Lee Y-E, Kim J-H, Cho M-J, et al. Effect of xylitol on dental caries prevention: a literature review. J Korean Soc Dent Hyg. 2019;19(4):449–465.
   Google Scholar
• van Loveren C. Sugar alcohols: what is the evidence for caries-preventive and caries-Therapeutic Effects? Caries Res. 2004;38(3):286–293. doi: 10.1159/000077768
   PubMed Web of Science ®Google Scholar
• Rafeek R, Carrington CV, Gomez A, et al. Xylitol and sorbitol effects on the microbiome of saliva and plaque. J Oral Microbiol. 2019;11(1):1536181. doi: 10.1080/20002297.2018.1536181
   PubMed Web of Science ®Google Scholar
• Takahashi N, Washio J. Metabolomic effects of xylitol and fluoride on plaque biofilm in vivo. J Dent Res. 2011;90(12):1463–8. doi: 10.1177/0022034511423395
   PubMed Web of Science ®Google Scholar
• Maehara H, Iwami Y, Mayanagi H, et al. Synergistic inhibition by combination of fluoride and xylitol on glycolysis by mutans streptococci and its biochemical mechanism. Caries Res. 2005;39(6):521–528. doi: 10.1159/000088190
   PubMed Web of Science ®Google Scholar
• Chen HW, Zhou W, Liao Y, et al. Analysis of metabolic profiles of generalized aggressive periodontitis. J Periodont Res. 2018;53(5):894–901. doi: 10.1111/jre.12579
   PubMed Web of Science ®Google Scholar
• Barnes V, Ciancio S, Shibly O, et al. Metabolomics reveals elevated macromolecular degradation in periodontal disease. J Dent Res. 2011;90(11):1293–7. doi: 10.1177/0022034511416240
   PubMed Web of Science ®Google Scholar
• Takahashi N, Sato T. Dipeptide utilization by the periodontal pathogens Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum. Oral Microbiol Immun. 2002;17(1):50–54. doi: 10.1046/j.0902-0055.2001.00089.x
   PubMedGoogle Scholar
• Baima G, Corana M, Iaderosa G, et al. Metabolomics of gingival crevicular fluid to identify biomarkers for periodontitis: a systematic review with meta-analysis. J Periodont Res. 2021;56(4):633–45. doi: 10.1111/jre.12872
   PubMed Web of Science ®Google Scholar
• Kuboniwa M, Sakanaka A, Hashino E, et al. Prediction of periodontal inflammation via metabolic profiling of saliva. J Dent Res. 2016;95(12):1381–6. doi: 10.1177/0022034516661142
   PubMed Web of Science ®Google Scholar
• Lee CT, Li R, Zhu L, et al. Subgingival microbiome and specialized pro-resolving lipid mediator pathway profiles are correlated in periodontal inflammation. Front Immunol. 2021;12:691216. doi: 10.3389/fimmu.2021.691216
   PubMed Web of Science ®Google Scholar
• Guan X, Li W, Meng H. A double-edged sword: role of butyrate in the oral cavity and the gut. Mol Oral Microbiol. 2021;36(2):121–31. doi: 10.1111/omi.12322
   PubMed Web of Science ®Google Scholar
• Haque MM, Yerex K, Kelekis-Cholakis A, et al. Advances in novel therapeutic approaches for periodontal diseases. BMC Oral Health. 2022;22(1):492. doi: 10.1186/s12903-022-02530-6
   PubMed Web of Science ®Google Scholar
• Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, et al. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition. 2012;28(5):539–43. doi: 10.1016/j.nut.2011.08.013
   PubMed Web of Science ®Google Scholar
• Chakraborty B, Burne RA, Liu S-J. Effects of arginine on Streptococcus mutans growth, virulence gene expression, and stress tolerance. Appl Environ Microbiol. 2017;83(15). doi: 10.1128/AEM.00496-17
   Web of Science ®Google Scholar
• Ishikawa KH, Mita D, Kawamoto D, et al. Probiotics alter biofilm formation and the transcription of Porphyromonas gingivalis virulence-associated genes. J Oral Microbiol. 2020;12(1):1805553. doi: 10.1080/20002297.2020.1805553
   PubMedGoogle Scholar
• Verspecht T, Van Holm W, Boon N, et al. Potential prebiotic substrates modulate composition, metabolism, virulence and inflammatory potential of an in vitro multi-species oral biofilm. J Oral Microbiol. 2021;13(1):1910462. doi: 10.1080/20002297.2021.1910462
   PubMed Web of Science ®Google Scholar
• Verspecht T, Van Holm W, Boon N, et al. Comparison of the modulatory effects of three structurally similar potential prebiotic substrates on an in vitro multi-species oral biofilm. Sci Rep. 2021;11(1):15033. doi: 10.1038/s41598-021-94510-z
   PubMed Web of Science ®Google Scholar
• Wasfi R, Abd El-Rahman OA, Zafer MM, et al. Probiotic Lactobacillus sp. inhibit growth, biofilm formation and gene expression of caries-inducing Streptococcus mutans. J Cellular Molecular Medi. 2018;22(3):1972–1983. doi: 10.1111/jcmm.13496
   PubMed Web of Science ®Google Scholar
• AC G, Yucel-Lindberg T, Roos S, et al. Effect of Lactobacillus reuteri on cell viability and PGE2 production in human gingival fibroblasts. Probiotics & Antimicro Prot. 2017;9(3):278–283. doi: 10.1007/s12602-016-9246-6
   PubMed Web of Science ®Google Scholar
• Aimetti M, Cacciatore S, Graziano A, et al. Metabonomic analysis of saliva reveals generalized chronic periodontitis signature. Metabolomics. 2012;8(3):465–74. doi: 10.1007/s11306-011-0331-2
   Web of Science ®Google Scholar
• Traudt M, Kleinberg I. Stoichiometry of oxygen consumption and sugar, organic acid and amino acid utilization in salivary sediment and pure cultures of oral bacteria. Arch Oral Biol. 1996;41(10):965–78. doi: 10.1016/S0003-9969(96)00044-1
   PubMed Web of Science ®Google Scholar
• Andörfer L, Holtfreter B, Weiss S, et al. Salivary metabolites associated with a 5-year tooth loss identified in a population-based setting. BMC Med. 2021;19(1):161. doi: 10.1186/s12916-021-02035-z
   PubMed Web of Science ®Google Scholar
• Schulte F, King OD, Paster BJ, et al. Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease. Metabolomics. 2020;16(9):1–11. doi: 10.1007/s11306-020-01719-6
   Web of Science ®Google Scholar
• Beck LC, Masi AC, Young GR, et al. Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants. Nat Microbiol. 2022;7(10):1525–35. doi: 10.1038/s41564-022-01213-w
   PubMed Web of Science ®Google Scholar