記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and Objectives: Our previous study demonstrated using an oral gavage model that Porphyromonas gingivalis could induce various inflammatory changes linked to periodontitis-associated systemic diseases by altering gut microbiota. A ligature-induced periodontitis model is similar to human periodontitis in various aspects: in both cases, alveolar bone resorption depends on oral bacterial load, and gingival tissue becomes infiltrated with inflammatory cells. Therefore, this model may be suitable for the analysis of bacterial burden and gingival tissue inflammation with changes related to systemic diseases.
Material and Methods: Periodontal tissue destruction was induced by a 2 wk ligature placement around the bilateral maxillary second molar. We analyzed the expression profile of various genes in several tissues, levels of systemic inflammatory markers and induction of insulin resistance. In addition, we studied changes in gut microbiota composition and bacterial load in the oral cavity.
Results: Two weeks after ligature placement gingival inflammation was significantly induced with a disrupted gingival epithelial barrier and alveolar bone resorption accompanied by increased bacterial burden in the oral cavity. Gene expression analysis of the gingival tissue of ligated mice demonstrated that interleukin (Il) 1b was significantly elevated and Il6 and Il17a tended to be higher in ligated mice than in untreated mice. Although serum IL-6 was significantly elevated and serum amyloid A tended to be higher in ligated compared to untreated mice, endotoxin levels did not differ between the two groups. Among the genes whose expressions are closely related to glucose and lipid metabolisms, only phosphoenolpyruvate carboxykinase 1 (Pck1) and acetyl-coenzyme A carboxylase alpha (Acaca) showed significant changes following ligature placement in the liver, with the former upregulated and the latter downregulated. However, insulin sensitivity did not change following ligature placement. Furthermore, ligature placement weakly affected the composition of gut microbiota and gene expression in the intestines.
Conclusion: The results suggest that increased oral commensals and gingival inflammation have limited roles in the pathological changes to adipose and liver tissues, which are important organs whose dysfunctions contribute to the development of periodontitis-related systemic diseases.

DOI： 10.1111/jre.12344

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Periodontitis has been implicated as a risk factor for metabolic disorders associated with insulin resistance. Recently, we have demonstrated that orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, induces endotoxemia via reduced gut barrier function coupled with changes in gut microbiota composition, resulting in systemic inflammation and insulin resistance. Propolis, a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants, can positively affect metabolic disorders in various experimental models. In this study, we thus aimed to clarify the effect of propolis on impaired glucose and lipid metabolism induced by P. gingivalis administration.
Methods: Eight-week-old male C57BL/6 mice were orally administered P. gingivalis strain W83, propolis ethanol extract powder with P. gingivalis, or vehicle. We then analyzed the expression profile of glucose and lipid metabolism-related genes in the liver and adipose tissues. Serum endotoxin levels were also evaluated by a limulus amebocyte lysate test. In addition, we performed histological analysis of the liver and quantified alveolar bone loss by measuring the root surface area on the lower first molar.
Results: Oral administration of P. gingivalis induced downregulation of genes that improve insulin sensitivity in adipose tissue (C1qtnf9, Irs1, and Sirt1), but upregulation of genes associated with lipid droplet formation and gluconeogenesis (Plin2, Acox, and G6pc). However, concomitant administration of propolis abrogated these adverse effects of P. gingivalis. Consistent with gene expression, histological analysis showed that administered propolis suppressed hepatic steatosis induced by P. gingivalis. Furthermore, propolis inhibited the elevation of serum endotoxin levels induced by P. gingivalis administration. Contrary to the systemic effects, propolis had no beneficial effect on alveolar bone loss.
Conclusion: These results suggest that administration of propolis may be effective in suppressing periodontopathic bacteria-induced metabolic changes that increase the risk of various systemic diseases.

DOI： 10.1186/s12906-016-1305-8

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その他リンク： http://orcid.org/0000-0002-2875-2111

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate.

DOI： 10.1128/AAC.02575-15

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その他リンク： http://orcid.org/0000-0002-2875-2111

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Although periodontitis has been implicated as a risk factor for various systemic diseases, the precise mechanisms by which periodontitis induces systemic disease remain to be elucidated. We have previously revealed that repeated oral administration of Porphyromonas gingivalis elicits endotoxemia via changes in the gut microbiota of the ileum, and thereby induces systemic inflammation and insulin resistance. However, it is not clear to what extent a single administration of P. gingivalis could affect gut microbiota composition, gut barrier function, and subsequent influx of gut microbiota into the liver. Therefore, in the present study, C57BL/6 mice were orally administered P. gingivalis (strain W83) once and compared to sham-inoculated mice. The phylogenetic structure and diversity of microbial communities in the gut and liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum endotoxin activity was determined by a Limulus amebocyte lysate test. Gene expression in the intestine and expression of 16S rRNA genes in the blood and liver were examined by quantitative polymerase chain reaction. Administration of P. gingivalis significantly altered gut microbiota, with an increased proportion of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and increased serum endotoxin levels. In the intestinal tissues, gene expression of tjp-1 and occludin, which are involved in intestinal permeability, were downregulated. Higher amounts of bacterial DNA were detected in the liver of infected mice. Importantly, changes in gut microbiota preceded systemic inflammatory changes. These results further support the idea that disturbance of the gut microbiota composition by orally derived periodontopathic bacteria may be a causal mechanism linking periodontitis and systemic disease.

DOI： 10.1371/journal.pone.0134234

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その他リンク： http://orcid.org/0000-0002-2875-2111

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance, and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis, a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis-administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis-administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases.

DOI： 10.1038/srep04828

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その他リンク： http://orcid.org/0000-0002-2875-2111

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Objectives: This study aims to clarify whether gingival fibroblasts produce periostin in response to Th2 cytokines which are elevated in periodontitis lesion and, if so, whether periostin affects the inflammatory response and matrix-protein metabolism.
Design: Human gingival fibroblasts, periodontal ligament cells and the gingival epithelial cell line epi4 were stimulated with interleukin-4 (IL-4), IL-13, tumour necrosis factor-alpha (TNF-alpha) and Porphyromonas gingivalis lipopolysaccharide (LPS). Periostin expression was analysed by real-time polymerase chain-reaction (PCR) and Western blotting. The expression of the IL-4 receptor alpha-chain was evaluated by immunocytochemistry. The effect of periostin on the production of inflammatory cytokines and the expression of matrix protein-related genes was analysed by real-time PCR and enzyme-linked immunosorbent assay (ELISA).
Results: While IL-4 and IL-13 significantly induced periostin production in gingival fibroblasts and periodontal ligament cells, no effect was observed in epi4 cells. No stimulatory effect of TNF-alpha or P. gingivalis LPS on the production of periostin was observed. The effect of periostin on the production of inflammatory cytokines was weak in gingival fibroblasts; however, little or no effect was observed on periodontal ligament cells or epi4 cells. No significant effect of periostin on the expression of matrix protein-related genes was found.
Conclusion: The results suggest that gingival fibroblasts may be a source of periostin in periodontitis lesions but periostin has only a limited role either in the inflammatory response or in matrix-protein metabolism. Thus, the role of periostin in the cellular interaction between epithelial and mesenchymal cells in gingiva may be distinct from that of skin. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2013.10.004

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その他リンク： http://orcid.org/0000-0002-2875-2111

記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

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記述言語：日本語   出版者・発行元：新潟歯学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：日本語   出版者・発行元：新潟歯学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

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記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

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記述言語：日本語   出版者・発行元：新潟歯学会  

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記述言語：日本語   出版者・発行元：(公財)日本ビフィズス菌センター  

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記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

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