Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Periodontol. 2019 Dec;90(12):1470-1480. doi: 10.1002/JPER.19-0130. Epub 2019 Sep 12.
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.
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 (10 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.
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.
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.
肠道细菌产生的生物活性代谢产物 KetoC 具有多种有益作用。然而，其在牙周炎发病机制中的作用尚不清楚。在此，我们研究了 KetoC 在牙周炎小鼠模型中的作用，并探讨了其潜在机制。
31 只 8 周龄雄性 C57BL/6N 小鼠随机分为四组（非结扎、非结扎+ KetoC、结扎+牙龈卟啉单胞菌和结扎+牙龈卟啉单胞菌+ KetoC）（n=7/8 只/组），并给予 KetoC（15mg/ml）或载体每日口服灌胃 2 周。为诱导牙周炎，于第 7 天在左侧上颌第二磨牙上放置 5-0 丝线结扎，每 3 天口服给予牙龈卟啉单胞菌 W83（10 个集落形成单位[CFU]）。第 14 天处死所有小鼠。从牙釉质-牙骨质交界到牙槽嵴的水平确定牙槽骨破坏程度。此外，从苏木精和伊红染色的牙龈组织切片中确认骨损失水平。使用实时聚合酶链反应定量检测牙龈卟啉单胞菌的存在。体外，通过分析 KetoC 对牙龈卟啉单胞菌增殖的抑制活性及其对活/死细菌染色试剂盒的抑菌和杀菌作用来评估 KetoC 的抑菌和杀菌作用。然后使用双键缺陷代谢物（KetoB）来研究双键结构在 KetoC 对牙龈卟啉单胞菌的抗菌活性中的重要性。
体内，KetoC 减轻了牙周炎组的牙槽骨破坏并抑制了牙龈卟啉单胞菌。体外，KetoC（而非 KetoB）以剂量依赖性方式下调牙龈卟啉单胞菌的增殖和活力。
KetoC 通过其抗菌功能减少了牙周炎模型中的牙槽骨破坏。因此，这种生物活性代谢物在支持牙周治疗的临床应用中可能具有价值。
