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

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.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…They summarized that oral gavage or a combination of oral gavage and ligature-induction might be a good strategy for studying inflammatory markers and epigenetic changes in experimental periodontal disease and better for modeling human periodontal disease compared to the simple ligature model. In addition to the aforementioned methods, there is another method to promote periodontitis by orally administering P. gingivalis to a ligature-induced periodontitis model; however, few studies have used this method, and it may not be considered to be a common way to induce periodontitis [175,192].…”

Probiotics-Mediated Bioconversion and Periodontitis

“…Anti-inflammatory activity has become a treatment strategy for periodontitis ( Sulijaya et al, 2019 ). Fermented milk with Lactobacillus helveticus LH-2 and its fraction peptide F5 increased TNF-α, IL-1β, and IL-6 through stimulation of macrophages with production of nitric oxide and phagocytic activity, which showed that the F5 peptide fraction could modulate macrophage functions ( Tellez et al, 2010 ).…”

“…Glycosylated caseinomacropeptide, produced by hydrolyzing the κ-casein phenylalanine-105 and methionine-106 peptide bonds by the action of chymosin in the process of milk fermentation, inhibited the entry of toxins, pathogenic adhesion to the cell wall, and infections by oral pathogens such as P. gingivalis, S. mutans, and Streptococcus sobrinus ( Córdova-Dávalos et al, 2019 ; Malkoski et al, 2001 ). KetoC inhibited the growth of P. gingivalis in vitro and reduced alveolar bone destruction in a periodontitis mouse model ( Sulijaya et al, 2019 ). Furthermore, fluorescence microscopy after LIVE/DEAD bacterial staining of KetoC-treated P. gingivalis cells showed that KetoC decreased the viability of the bacteria ( Sulijaya et al, 2019 ).…”

“…KetoC inhibited the growth of P. gingivalis in vitro and reduced alveolar bone destruction in a periodontitis mouse model ( Sulijaya et al, 2019 ). Furthermore, fluorescence microscopy after LIVE/DEAD bacterial staining of KetoC-treated P. gingivalis cells showed that KetoC decreased the viability of the bacteria ( Sulijaya et al, 2019 ). In addition, a comparative analysis of the inhibitory effects of KetoC and KetoB against P. gingivalis showed that only KetoC lowered the viability and proliferation rate of P. gingivalis ( Sulijaya et al, 2019 ).…”

“…Furthermore, fluorescence microscopy after LIVE/DEAD bacterial staining of KetoC-treated P. gingivalis cells showed that KetoC decreased the viability of the bacteria ( Sulijaya et al, 2019 ). In addition, a comparative analysis of the inhibitory effects of KetoC and KetoB against P. gingivalis showed that only KetoC lowered the viability and proliferation rate of P. gingivalis ( Sulijaya et al, 2019 ). According to Lee et al (2020) study, PMB of whey showed anti-biofilm effect against pathogenic bacteria.…”