TY - JOUR
T1 - Elimination of Porphyromonas gingivalis inhibits liver fibrosis and inflammation in NASH
AU - Nagasaki, Atsuhiro
AU - Sakamoto, Shinnichi
AU - Arai, Toshiki
AU - Kato, Minami
AU - Ishida, Eri
AU - Furusho, Hisako
AU - Fujii, Makiko
AU - Takata, Takashi
AU - Miyauchi, Mutsumi
N1 - Funding Information:
We thank Dr. Kazuhisa Ouhara (Department of Periodontal Medicine, Graduate school of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) for providing W83 strain and also Prof. Kazuyuki Ishihara (Tokyo Dental University Microbiology Course, Tokyo, Japan) for providing anti‐ polyclonal antibody. Atsuhiro Nagasaki was a recipient of the Iwadare Scholarship in 2016. This work was supported by the Grants‐in‐Aid for Scientific Research Scientific Research (C) (No. 25462855) to M.M. Porphyromonas gingivalis Porphyromonas gingivalis
Funding Information:
We thank Dr. Kazuhisa Ouhara (Department of Periodontal Medicine, Graduate school of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan) for providing Porphyromonas gingivalis W83 strain and also Prof. Kazuyuki Ishihara (Tokyo Dental University Microbiology Course, Tokyo, Japan) for providing anti-Porphyromonas gingivalis polyclonal antibody. Atsuhiro Nagasaki was a recipient of the Iwadare Scholarship in 2016. This work was supported by the Grants-in-Aid for Scientific Research Scientific Research (C) (No. 25462855) to M.M.
Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021/10
Y1 - 2021/10
N2 - Aim: Non-alcoholic steatohepatitis (NASH) is a critical liver disease showing potential progression to liver cirrhosis/cancer. Previously, we had reported that odontogenic infection of Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, exacerbates fibrosis in NASH through the production of fibrosis mediators such as transforming growth factor-β1 (TGF-β1) and galectin-3. In this study, we determined the effects of therapeutic interventions using antibiotics on NASH progression induced by P. gingivalis odontogenic infection. Materials and methods: To eliminate P. gingivalis infection, the macrolide antibiotic [azithromycin (AZM)] was applied locally and/or systemically to a high-fat-diet-induced NASH mouse model with P. gingivalis odontogenic infection. After treatment with AZM, liver and periodontal tissues were analysed with focus on inflammation markers such as tumour necrosis factor-α (TNF-α)/Tnf-α and interleukin-1β (IL-1β)/Il-1β, and fibrosis markers such as galectin-3, phosphorylated Smad2 (pSmad2; key signalling molecule of TGF-β1), and the number of hepatic crown-like structures (hCLSs). Further, Non-alcoholic Fatty Liver Disease Activity Score (NAS), a common histological scoring system, and fibrosis area were evaluated. Results: P. gingivalis odontogenic infection significantly increased the expression of Tnf-α, Il-1β, galectin-3, and pSmad2, the number of hCLSs, and NAS score, whereas the elimination of P. gingivalis odontogenic infection, especially local with or without systemic application, significantly inhibited them. Conclusion: This study suggests that elimination of P. gingivalis odontogenic infection inhibited NASH progression induced by the infection.
AB - Aim: Non-alcoholic steatohepatitis (NASH) is a critical liver disease showing potential progression to liver cirrhosis/cancer. Previously, we had reported that odontogenic infection of Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, exacerbates fibrosis in NASH through the production of fibrosis mediators such as transforming growth factor-β1 (TGF-β1) and galectin-3. In this study, we determined the effects of therapeutic interventions using antibiotics on NASH progression induced by P. gingivalis odontogenic infection. Materials and methods: To eliminate P. gingivalis infection, the macrolide antibiotic [azithromycin (AZM)] was applied locally and/or systemically to a high-fat-diet-induced NASH mouse model with P. gingivalis odontogenic infection. After treatment with AZM, liver and periodontal tissues were analysed with focus on inflammation markers such as tumour necrosis factor-α (TNF-α)/Tnf-α and interleukin-1β (IL-1β)/Il-1β, and fibrosis markers such as galectin-3, phosphorylated Smad2 (pSmad2; key signalling molecule of TGF-β1), and the number of hepatic crown-like structures (hCLSs). Further, Non-alcoholic Fatty Liver Disease Activity Score (NAS), a common histological scoring system, and fibrosis area were evaluated. Results: P. gingivalis odontogenic infection significantly increased the expression of Tnf-α, Il-1β, galectin-3, and pSmad2, the number of hCLSs, and NAS score, whereas the elimination of P. gingivalis odontogenic infection, especially local with or without systemic application, significantly inhibited them. Conclusion: This study suggests that elimination of P. gingivalis odontogenic infection inhibited NASH progression induced by the infection.
KW - Porphyromonas gingivalis
KW - dental infection control
KW - non-alcoholic steatohepatitis
KW - periodontitis
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U2 - 10.1111/jcpe.13523
DO - 10.1111/jcpe.13523
M3 - Article
C2 - 34250613
AN - SCOPUS:85112670754
VL - 48
SP - 1367
EP - 1378
JO - Journal of Clinical Periodontology
JF - Journal of Clinical Periodontology
SN - 0303-6979
IS - 10
ER -