, Volume 23, Issue 3, pp 419–424 | Cite as

Periodontitis, periodontopathic bacteria and lactoferrin

  • Hiroyuki Wakabayashi
  • Ichiro Kondo
  • Tetsuo Kobayashi
  • Koji Yamauchi
  • Tomohiro Toida
  • Keiji Iwatsuki
  • Hiromasa Yoshie


Lactoferrin (LF) is a component of saliva and is suspected to be a defense factor against oral pathogens including Streptococcus mutans and Candida albicans. Periodontitis is a very common oral disease caused by periodontopathic bacteria. Antimicrobial activities and other biological effects of LF against representative periodontopathic bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, have been widely studied. Association of polymorphisms in LF with incidence of aggressive periodontitis and the role of LF in the gingival crevicular fluid as a marker of periodontitis severity have also been reported. Periodontopathic bacteria reside as a biofilm in supragingival and subgingival plaque. Our recent study indicated that LF exhibits antibacterial activity against planktonic forms of P. gingivalis and P. intermedia at higher concentrations, and furthermore, LF effectively inhibits biofilm formation and reduces the established biofilm of these bacteria at physiological concentrations. A small-scale clinical study indicated that oral administration of bovine LF reduces P. gingivalis and P. intermedia in the subgingival plaque of chronic periodontitis patients. LF seems to be a biofilm inhibitor of periodontopathic bacteria in vitro and in vivo.


Lactoferrin Periodontitis Periodontopathic bacteria Plaque Biofilm 


  1. Adonogianaki E, Moughal NA, Kinane DF (1993) Lactoferrin in the gingival crevice as a marker of polymorphonuclear leucocytes in periodontal diseases. J Clin Periodontol 20:26–31CrossRefPubMedGoogle Scholar
  2. Aguilera O, Andrés MT, Heath J, Fierro JF, Douglas CWI (1998) Evaluation of the antimicrobial effect of lactoferrin on Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens. FEMS Immunol Med Microbiol 21:29–36CrossRefPubMedGoogle Scholar
  3. Alugupalli KR, Kalfas S (1995) Inhibitory effect of lactoferrin on the adhesion of Actinobacillus actinomycetemcomitans and Prevotella intermedia to fibroblasts and epithelial cells. APMIS 103:154–160CrossRefPubMedGoogle Scholar
  4. Alugupalli KR, Kalfas S (1996) Degradation of lactoferrin by periodontitis-associated bacteria. FEMS Microbiol Lett 145:209–214CrossRefPubMedGoogle Scholar
  5. Alugupalli KR, Kalfas S, Edwardsson S, Forsgren A, Arnold RR, Naidu AS (1994) Effect of lactoferrin on interaction of Prevotella intermedia with plasma and subepithelial matrix proteins. Oral Microbiol Immunol 9:174–179CrossRefPubMedGoogle Scholar
  6. Al-Zahrani MS (2006) Increased intake of dairy products is related to lower periodontitis prevalence. J Periodontol 77:289–294CrossRefPubMedGoogle Scholar
  7. Baveye S, Elass E, Mazurier J, Spik G, Legrand D (1999) Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process. Clin Chem Lab Med 37:281–286CrossRefPubMedGoogle Scholar
  8. Chierici R (2001) Antimicrobial actions of lactoferrin. Adv Nutr Res 10:247–269PubMedGoogle Scholar
  9. Davey ME, Costerton JW. 2006 Molecular genetics analyses of biofilm formation in oral isolates. Periodontology 2000 42:3–26Google Scholar
  10. de Lillo A, Teanpaisan R, Fierro JF, Douglas CWI (1996) Binding and degradation of lactoferrin by Porphyromonas gingivalis, Prevotella intermedia and Prevotella nigrescens. FEMS Immunol Med Microbiol 14:135–143CrossRefPubMedGoogle Scholar
  11. Eberhard J, Drosos Z, Tiemann M, Jepsen S, Schröder JM (2006) Immunolocalization of lactoferrin in healthy and inflamed gingival tissues. J Periodontol 77:472–478CrossRefPubMedGoogle Scholar
  12. Fine DH, Furgang D (2002) Lactoferrin iron levels affect attachment of Actinobacillus actinomycetemcomitans to buccal epithelial cells. J Periodontol 73:616–623CrossRefPubMedGoogle Scholar
  13. Fine DH, Furgang D, Beydouin F (2002) Lactoferrin iron levels are reduced in saliva of patients with localized aggressive periodontitis. J Periodontol 73:624–630CrossRefPubMedGoogle Scholar
  14. Friedman SA, Mandel ID, Herrera MS (1983) Lysozyme and lactoferrin quantitation in the crevicular fluid. J Periodontol 54:347–350PubMedGoogle Scholar
  15. Jentsch H, Sievert Y, Göcke R (2004) Lactoferrin and other markers from gingival crevicular fluids and saliva before and after periodontal treatment. J Clin Periodontol 31:511–514CrossRefPubMedGoogle Scholar
  16. Jordan WJ, Eskdale J, Lennon GP, Pestoff R, Wu L, Fine DH, Gallagher G (2005) A nonconservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population. Genes Immun 6:632–635CrossRefPubMedGoogle Scholar
  17. Kalfas S, Andersson M, Edwardsson S, Forsgren A, Naidu AS (1991) Human lactoferrin binding to Porphyromonas gingivalis, Prevotella intermedia and Prevotella melaninogenica. Oral Microbiol Immunol 6:350–355CrossRefPubMedGoogle Scholar
  18. Kalmar JR, Arnold RR (1988) Killing of Actinobacillus actinomycetemcomitans by human lactoferrin. Infect Immun 56:2552–2557PubMedGoogle Scholar
  19. Komine K-I, Kuroishi T, Ozawa A, Komine Y, Minami T, Shimauchi H, Sugawara S (2007) Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients. Mol Immunol 44:1498–1508CrossRefPubMedGoogle Scholar
  20. Kondo I, Kobayashi T, Wakabayashi H, Yamauchi K, Iwatsuki K, Yoshie H (2008) Effects of oral administration of bovine lactoferrin on periodontitis patients. Jpn J Conserv Dent 51:281–291 (in Japanese)Google Scholar
  21. Larsen T (2002) Susceptibility of Porphyromonas gingivalis in biofilms to amoxicillin, doxycycline and metronidazole. Oral Microbiol Immunol 17:267–271CrossRefPubMedGoogle Scholar
  22. Levay PF, Viljoen M (1995) Lactoferrin: a general review. Haematologica 80:252–267PubMedGoogle Scholar
  23. Loesche WJ (1999) The antimicrobial treatment of periodontal disease: change the treatment paradigm. Crit Rev Oral Biol Med 10:245–275CrossRefPubMedGoogle Scholar
  24. Marsh PD (1992) Microbiological aspects of the chemical control of plaque and gingivitis. J Dent Res 71:1431–1438PubMedGoogle Scholar
  25. Mayanagi G, Kimura M, Nakaya S, Hirata H, Sakamoto M, Benno Y, Shimauchi H (2009) Probiotic effects of orally administered Lactobacillus salivarius WB21-containing tablets: a double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol 36:506–513CrossRefPubMedGoogle Scholar
  26. Ozdemir B, Ozcan G, Karaduman B, Teoman AI, Ayhan E, Ozer N, Us D (2009) Lactoferrin in gingival crevicular fluid and peripheral blood during experimental gingivitis. Eur J Dent 3:16–23PubMedGoogle Scholar
  27. Shi Y, Kong W, Nakayama K (2000) Human lactoferrin binds and removes the hemoglobin receptor protein of the periodontopathogen Porphyromonas gingivalis. J Biol Chem 275:30002–30008CrossRefPubMedGoogle Scholar
  28. Shimauchi H, Mayanagi G, Nakaya S, Minamibuchi M, Ito Y, Yamaki K, Hirata H (2008) Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized, double-blind, placebo-controlled study. J Clin Periodontol 35:897–905CrossRefPubMedGoogle Scholar
  29. Shimazaki Y, Shirota T, Uchida K, Yonemoto K, Kiyohara Y, Iida M, Saito T, Yamashita Y (2008) Intake of dairy products and periodontal disease: The Hisayama study. J Periodontol 79:131–137CrossRefPubMedGoogle Scholar
  30. Sojar HT, Hamada N, Genco RJ (1998) Structures involved in the interaction of Porphyromonas gingivalis fimbriae and human lactoferrin. FEBS Lett 422:205–208CrossRefPubMedGoogle Scholar
  31. Takahashi N, Ishihara K, Kimizuka R, Okuda K, Kato T (2006) The effects of tetracycline, minocycline, doxycycline and ofloxacin on Prevotella intermedia biofilm. Oral Microbiol Immunol 21:366–371CrossRefPubMedGoogle Scholar
  32. Takakura N, Wakabayashi H, Ishibashi H, Teraguchi S, Tamura Y, Yamaguchi H, Abe S (2003) Oral lactoferrin treatment of experimental oral candidiasis in mice. Antimicrob Agents Chemother 47:2619–2623CrossRefPubMedGoogle Scholar
  33. Tenovuo J (2002) Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety. Oral Dis 8:23–29CrossRefPubMedGoogle Scholar
  34. Velliyagounder K, Kaplan JB, Furgang D, Legarda D, Diamond G, Parkin RE, Fine DH (2003) One of two human lactoferrin variants exhibits increased antibacterial and transcriptional activation activities and is associated with localized juvenile periodontitis. Infect Immun 71:6141–6147CrossRefPubMedGoogle Scholar
  35. Wakabayashi H, Abe S, Teraguchi S, Hayasawa H, Yamaguchi H (1998) Inhibition of hyphal growth of azole-resistant strains of Candida albicans by triazole antifungal agents in the presence of lactoferrin-related compounds. Antimicrob Agents Chemother 42:1587–1591PubMedGoogle Scholar
  36. Wakabayashi H, Yamauchi K, Kobayashi T, Yaeshima T, Iwatsuki K, Yoshie H (2009) Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia. Antimicrob Agents Chemother 53:3308–3316CrossRefPubMedGoogle Scholar
  37. Wu Y-M, Juo S-H, Ho Y-P, Ho K-Y, Yang Y-H, Tsai C-C (2009) Association between lactoferrin gene polymorphisms and aggressive periodontitis among Taiwanese patients. J Periodont Res 44:418–424CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Hiroyuki Wakabayashi
    • 1
  • Ichiro Kondo
    • 2
  • Tetsuo Kobayashi
    • 2
    • 3
  • Koji Yamauchi
    • 1
  • Tomohiro Toida
    • 1
  • Keiji Iwatsuki
    • 1
  • Hiromasa Yoshie
    • 2
  1. 1.Food Science and Technology InstituteMorinaga Milk Industry Co., LtdZamaJapan
  2. 2.Division of PeriodontologyNiigata University Graduate School of Medical and Dental SciencesNiigata-CityJapan
  3. 3.General Dentistry and Clinical Education UnitNiigata University Medical and Dental HospitalNiigata-CityJapan

Personalised recommendations