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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

Periodontal Diseases
Cadherins
Bacteria
Fatty Acids
Porphyromonas gingivalis
Periodontitis
Microbiota
Probiotics
beta Catenin
Intestines
Theoretical Models
Epithelial Cells
10-hydroxy-12-octadecenoic acid
12-octadecenoic acid
Cytokines
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling. / Yamada, Miki; Takahashi, Naoki; Matsuda, Yumi; Sato, Keisuke; Yokoji, Mai; Sulijaya, Benso; Maekawa, Tomoki; Ushiki, Tatsuo; Mikami, Yoshikazu; Hayatsu, Manabu; Mizutani, Yusuke; Kishino, Shigenobu; Ogawa, Jun; Arita, Makoto; Tabeta, Koichi; Maeda, Takeyasu; Yamazaki, Kazuhisa.

In: Scientific Reports, Vol. 8, No. 1, 9008, 01.12.2018.

Research output: Contribution to journalArticle

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, vol. 8, no. 1, 9008. https://doi.org/10.1038/s41598-018-27408-y
Yamada, Miki ; Takahashi, Naoki ; Matsuda, Yumi ; Sato, Keisuke ; Yokoji, Mai ; Sulijaya, Benso ; Maekawa, Tomoki ; Ushiki, Tatsuo ; Mikami, Yoshikazu ; Hayatsu, Manabu ; Mizutani, Yusuke ; Kishino, Shigenobu ; Ogawa, Jun ; Arita, Makoto ; Tabeta, Koichi ; Maeda, Takeyasu ; Yamazaki, Kazuhisa. / A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{450d50e7a6934a91879c9b4e127ff918,
title = "A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling",
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.",
author = "Miki Yamada and Naoki Takahashi and Yumi Matsuda and Keisuke Sato and Mai Yokoji and Benso Sulijaya and Tomoki Maekawa and Tatsuo Ushiki and Yoshikazu Mikami and Manabu Hayatsu and Yusuke Mizutani and Shigenobu Kishino and Jun Ogawa and Makoto Arita and Koichi Tabeta and Takeyasu Maeda and Kazuhisa Yamazaki",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-27408-y",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling

AU - Yamada, Miki

AU - Takahashi, Naoki

AU - Matsuda, Yumi

AU - Sato, Keisuke

AU - Yokoji, Mai

AU - Sulijaya, Benso

AU - Maekawa, Tomoki

AU - Ushiki, Tatsuo

AU - Mikami, Yoshikazu

AU - Hayatsu, Manabu

AU - Mizutani, Yusuke

AU - Kishino, Shigenobu

AU - Ogawa, Jun

AU - Arita, Makoto

AU - Tabeta, Koichi

AU - Maeda, Takeyasu

AU - Yamazaki, Kazuhisa

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048546466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048546466&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-27408-y

DO - 10.1038/s41598-018-27408-y

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 9008

ER -