Antimicrobial function of the polyunsaturated fatty acid KetoC in an experimental model of periodontitis

Benso Sulijaya, Miki Yamada-Hara, Mai Yokoji-Takeuchi, Yumi Matsuda-Matsukawa, Kyoko Yamazaki, Aoi Matsugishi, Takahiro Tsuzuno, Keisuke Sato, Yukari Aoki-Nonaka, Naoki Takahashi, Shigenobu Kishino, Jun Ogawa, Koichi Tabeta, Kazuhisa Yamazaki

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

BACKGROUND: The bioactive metabolite KetoC, generated by intestinal bacteria, exerts various beneficial effects. Nevertheless, its function in the pathogenesis of periodontitis remains unclear. Here, we investigated the effect of KetoC in a mouse model of periodontitis and explored the underlying mechanism. METHODS: Thirty-one 8-week-old male C57BL/6N mice were randomly divided into four groups (non-ligation, non-ligation + KetoC, ligation + Porphyromonas gingivalis, and ligation + P. gingivalis + KetoC) (n = 7/8 mice/group) and given a daily oral gavage of KetoC (15 mg/mL) or vehicle for 2 weeks. To induce periodontitis, a 5-0 silk ligature was placed on the maxillary left second molar on day 7, and P. gingivalis W83 (109 colony-forming unit [CFU]) was administered orally every 3 days. On day 14, all mice were euthanized. Alveolar bone destruction was determined from the level of the cemento-enamel junction to the alveolar bone crest. Moreover, bone loss level was confirmed from gingival tissue sections stained with hematoxylin and eosin. The presence of P. gingivalis was quantified using real-time polymerase chain reaction. In vitro, the bacteriostatic and bactericidal effects of KetoC were assessed by analyzing its suppressive activity on the proliferation of P. gingivalis and using a live/dead bacterial staining kit, respectively. A double-bond-deficient metabolite (KetoB) was then used to investigate the importance of double-bond structure in the antimicrobial activity of KetoC on P. gingivalis. RESULTS: In vivo, KetoC attenuated alveolar bone destruction and suppressed P. gingivalis in the periodontitis group. In vitro, KetoC (but not KetoB) downregulated the proliferation and viability of P. gingivalis in a dose-dependent manner. CONCLUSIONS: KetoC reduced alveolar bone destruction in a periodontitis model via its antimicrobial function. Therefore, this bioactive metabolite may be valuable in clinical applications to support periodontal therapy.

Original languageEnglish
Pages (from-to)1470-1480
Number of pages11
JournalJournal of Periodontology
Volume90
Issue number12
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • antimicrobial
  • fatty acid
  • periodontitis
  • Porphyromonas gingivalis

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