Elimination of Porphyromonas gingivalis inhibits liver fibrosis and inflammation in NASH

Atsuhiro Nagasaki, Shinnichi Sakamoto, Toshiki Arai, Minami Kato, Eri Ishida, Hisako Furusho, Makiko Fujii, Takashi Takata, Mutsumi Miyauchi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1367-1378
Number of pages12
JournalJournal of Clinical Periodontology
Volume48
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • dental infection control
  • non-alcoholic steatohepatitis
  • periodontitis
  • Porphyromonas gingivalis

ASJC Scopus subject areas

  • Periodontics

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