A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling

Miki Yamada, Naoki Takahashi, Yumi Matsuda, Keisuke Sato, Mai Yokoji, Benso Sulijaya, Tomoki Maekawa, Tatsuo Ushiki, Yoshikazu Mikami, Manabu Hayatsu, Yusuke Mizutani, Shigenobu Kishino, Jun Ogawa, Makoto Arita, Koichi Tabeta, Takeyasu Maeda, Kazuhisa Yamazaki

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Abstract

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.

Original languageEnglish
Article number9008
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1
Externally publishedYes

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ASJC Scopus subject areas

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Cite this

Yamada, M., Takahashi, N., Matsuda, Y., Sato, K., Yokoji, M., Sulijaya, B., Maekawa, T., Ushiki, T., Mikami, Y., Hayatsu, M., Mizutani, Y., Kishino, S., Ogawa, J., Arita, M., Tabeta, K., Maeda, T., & Yamazaki, K. (2018). A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling. Scientific Reports, 8(1), [9008]. https://doi.org/10.1038/s41598-018-27408-y