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Objective: Through this work, we aimed to clarify the association between the severity of periodontitis and osteocalcin (OC) gene C298T polymorphismin Indonesian male subjects.Methods: DNA was extracted from blood serum samples of 100 consenting Indonesian men whose periodontitis was classified as mild, moderate,or severe. Polymerase chain reaction and restriction fragment length polymorphism techniques were applied to evaluate the status of OC (C298T)polymorphism using HindIII restriction enzyme and electrophoresis in agarose gel to separate the indicated fragments.Results: Although genotype distribution of the OC C298T polymorphism showed a trend for more frequent occurrence of genotype hh (and allele h)with increasing severity of periodontitis, this trend was not statistically significant in the tested sample population, in whom the HH genotypeappeared to be relatively rare.Conclusion: The results showed no significant association between the severity of periodontitis and OC C298T polymorphism in Indonesian malesubjects.

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.

Background: Gut microbiota plays a pivotal role in regulating host metabolism that affects the systemic health. To date, several studies have confirmed the fact that microbiota interacts with host, modulating immunity, controlling the homeostasis environment, and maintaining systemic condition. Recent studies have focused on the protective function of poly unsaturated fatty acids, 10-oxo-trans-11-oxadecenoic acid (KetoC) and 10-hydroxy-cis-12-octadecenoic acid (HYA), generated by gut microbiota on periodontal disease. Nevertheless, the mechanism remains unclear as investigations are limited to in vivo and in vitro studies. In this present review, we found that the administration of metabolites, KetoC and HYA, by a probiotic gut microbiota Lactobacillus plantarum from linoleic acid is found to inhibit the oxidation process, possess an antimicrobial function, and prevent the inflammation. These findings suggest the promising use of functional lipids for human health. Conclusion: Protective modalities of bioactive metabolites may support periodontal therapy by suppressing bacterial dysbiosis and regulating periodontal homeostasis in the clinical setting.

Objective This study aimed to evaluate the effects of ingested periodontal pathogens on experimental colitis in mice and to elucidate its underlying mechanisms. Background Inflammatory bowel disease (IBD) is defined as a chronic intestinal inflammation that results in damage to the gastrointestinal tract. Epidemiological studies have shown an association between IBD and periodontitis. Although a large number of ingested oral bacteria reach gastrointestinal tract constantly, the effect of ingested periodontal pathogens on intestinal inflammation is still unknown. Methods Experimental colitis was induced by inclusion of dextran sodium sulfate solution in drinking water of the mice. Major periodontal pathogens (Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum) were administered orally every day during the experiment. The severity of colitis between the groups was compared. In vitro studies of the intestinal epithelial cell line were conducted to explore the molecular mechanisms by which periodontal pathogens affect the development of colitis. Results The oral administration of P. gingivalis significantly increased the severity of colitis when compared to other pathogens in the DSS-induced colitis model. The ingested P. gingivalis disrupted the colonic epithelial barrier by decreasing the expression of tight junction proteins in vivo. In vitro permeability assays using the intestinal epithelial cell line suggested the P. gingivalis-specific epithelial barrier disruption. The possible involvement of gingipains in the exacerbation of colitis was implied by using P. gingivalis lacking gingipains. Conclusion Porphyromonas gingivalis exacerbates gastrointestinal inflammation by directly interacting with the intestinal epithelial barrier in a susceptible host.

Background There is rapidly developing interest into the role of several anti-inflammatory agents to resolve inflammation in periodontal disease. A bioactive polyunsaturated fatty acid, 10-oxo-trans-11-octadecenoic acid (KetoC), is known to have various beneficial physiological effects; however, the effect of KetoC on inflammation remains unclear. Here, we investigated the effect of KetoC on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide, and explored the intracellular mechanism responsible for its anti-inflammatory effects. Methods RAW 264.7 cells were pre-treated with or without KetoC, and then stimulated with or without P. gingivalis lipopolysaccharide. Levels of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Specific antagonists for G protein-coupled receptor (GPR)40 and GPR120 were used to clarify the receptor for KetoC. The intracellular mechanism was investigated using western blotting analysis to separate nuclear and cytosolic NF-κB p65 protein. Result KetoC (5 μmol/L) was not toxic to RAW 264.7 cells, and significantly reduced the expression of TNFα and IL-6 mRNA and protein, and IL-1β mRNA. No protein production of IL-1β was observed. Additionally, when bound to GPR120, KetoC trended to downregulate nuclear NF-κB p65 protein levels. However, the antagonist for GPR40 failed to diminish the action of KetoC. Conclusion KetoC suppressed the proinflammatory cytokines TNFα, IL-6 and IL-1β via NF-κB p65, by binding to its receptor GPR120. KetoC is a promising candidate in future studies as a bioactive anti-inflammatory agent in treating periodontal disease.

The gingival epithelium acts as a physical barrier to separate the biofilm from the gingival tissue, providing the first line of defense against bacterial invasion in periodontal disease. Disruption of the gingival epithelial barrier, and the subsequent penetration of exogenous pathogens into the host tissues, triggers an inflammatory response, establishing chronic infection. Currently, more than 700 different bacterial species have been identified in the oral cavity, some of which are known to be periodontopathic. These bacteria contribute to epithelial barrier dysfunction in the gingiva by producing several virulence factors. However, some bacteria in the oral cavity appear to be beneficial, helping gingival epithelial cells maintain their integrity and barrier function. This review aims to discuss current findings regarding microorganism interactions and epithelial barrier function in the oral cavity, with reference to investigations in the gut, where this interaction has been extensively studied.

Background and objectives Recent evidence suggests that oral bacteria can affect extra-oral diseases by modulating aspects of the gut environment such as the microbiome, metabolome, and immune profiles. However, differences in the effects of different types of oral bacteria, particularly periodontopathic and health-associated bacteria, remain elusive. Materials and methods Five-week-old germ-free mice were orally administered with either periodontopathic bacteria as oral pathobionts (Porphyromonas gingivalis, Filifactor alocis, and Fusobacterium nucleatum) or bacteria associated with periodontal health (Actinomyces naeslundii, Streptococcus mitis, and Veillonella rogosae) twice a week for five weeks. The presence of all bacterial species in the feces and the livers of the mice was analyzed via polymerase chain reaction (PCR), using specific primers for 16S rRNA genes. Alveolar bone resorption was evaluated histologically. The expression profiles of various genes in the liver and small intestine were analyzed using real-time PCR. Sera were analyzed to determine the levels of antibodies and endotoxin. The proportions of T helper 17 (Th17) and regulatory T (Treg) cells in mesenteric lymph nodes and Peyer's patches were analyzed using flow cytometry. Results Neither of the types of bacteria administered in this experiment induced alveolar bone resorption. All bacteria elicited some degree of systemic antibody response in the mice, although the response to S. mitis was not obvious. The response to P. gingivalis and V. rogosae was strongest. Generally, the health-associated bacteria but not the periodontitis-associated bacteria were detected in fecal samples. Interestingly, only Fusobacterium nucleatum DNA was detected in the liver, despite that live Fusobacterium nucleatum were not detected in the liver. The levels of interleukin-17 in the intestine and genes related to lipid accumulation in the liver were significantly higher in the mice that received periodontitis-associated bacteria. In addition, expression of the gene associated with endoplasmic reticulum stress was higher and that of the gene controlling circadian rhythm was lower in the periodontitis group. There was no difference in serum endotoxin, T-cell phenotypes in the lymphatic tissues, or genes related to the gut barrier. Conclusion Oral administration of periodontitis-associated bacteria can induce pathological changes in the liver and intestine that are implicated in the process of periodontitis. These findings further support the importance of the oral–gut connection.

Background Periodontitis is an inflammatory disease that results in alveolar bone resorption due to inflammatory cytokine production induced by bacterial antigens such as lipopolysaccharides (LPS). Here, the preventive effect of the Amyl-1-18 peptide derived from rice in an experimental model of periodontitis and the effect on the anti-inflammatory response were assessed. Methods Alveolar bone resorption, gene transcription of proinflammatory cytokines in the gingiva, and the endotoxin level in the oral cavity were evaluated after oral administration of the Amyl-1-18 peptide for 14 days using a ligature-induced periodontitis model in mice. Additionally, murine macrophages were incubated with LPS of Escherichia coli or Porphyromonas gingivalis in the presence of Amyl-1-18 to analyze the suppressive effects of Amyl-1-18 on the cell signaling pathways associated with proinflammatory cytokine production, including inflammasome activities. Results Oral administration of Amyl-1-18 suppressed alveolar bone resorption and gene transcription of interleukin (il)6 in the gingiva of the periodontitis model, and decreased endotoxin levels in the oral cavity, suggesting modulation of periodontal inflammation by inhibition of endotoxin activities in vivo. Also, Amyl-1-18 suppressed IL-6 production induced by LPS and recombinant IL-1β in macrophages in vitro but had no effect on inflammasome activity. Conclusions The Amyl-1-18 peptide from rice inhibited alveolar bone destruction in mouse periodontitis model via suppressing inflammatory cytokine production induced by LPS. It was suggested that Amyl-1-18 peptide has anti-inflammatory property against LPS, not only by neutralization of LPS and subsequent inhibition of nuclear factor-κB signaling but also by inhibition of the IL-1R-related signaling cascade.

Several studies have demonstrated the remarkable properties of microbiota and their metabolites in the pathogenesis of several inflammatory diseases. 10-Hydroxy-cis-12-octadecenoic acid (HYA), a bioactive metabolite generated by probiotic microorganisms during the process of fatty acid metabolism, has been studied for its protective effects against epithelial barrier impairment in the intestines. Herein, we examined the effect of HYA on gingival epithelial barrier function and its possible application for the prevention and treatment of periodontal disease. We found that GPR40, a fatty acid receptor, was expressed on gingival epithelial cells; activation of GPR40 by HYA significantly inhibited barrier impairment induced by Porphyromonas gingivalis, a representative periodontopathic bacterium. The degradation of E-cadherin and beta-catenin, basic components of the epithelial barrier, was prevented in a GPR40-dependent manner in vitro. Oral inoculation of HYA in a mouse experimental periodontitis model suppressed the bacteria-induced degradation of E-cadherin and subsequent inflammatory cytokine production in the gingival tissue. Collectively, these results suggest that HYA exerts a protective function, through GPR40 signaling, against periodontopathic bacteria-induced gingival epithelial barrier impairment and contributes to the suppression of inflammatory responses in periodontal diseases.