Journal of Gastroenterology

, Volume 48, Issue 11, pp 1259–1270 | Cite as

Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice

  • Hisako Furusho
  • Mutsumi MiyauchiEmail author
  • Hideyuki Hyogo
  • Toshihiro Inubushi
  • Min Ao
  • Kazuhisa Ouhara
  • Junzou Hisatune
  • Hidemi Kurihara
  • Motoyuki Sugai
  • C. Nelson Hayes
  • Takashi Nakahara
  • Hiroshi Aikata
  • Shoichi Takahashi
  • Kazuaki Chayama
  • Takashi TakataEmail author
Original Article—Liver, Pancreas, and Biliary Tract



We investigated the effects of dental infection with Porphyromonas gingivalis (P.g.), an important periodontal pathogen, on NASH progression, by feeding mice a high fat diet (HFD)and examining P.g. infection in the liver of NASH patients.


C57BL/6J mice were fed either chow-diet (CD) or HFD for 12 weeks, and then half of the mice in each group were infected with P.g. from the pulp chamber (HFD-P.g.(−), HFD-P.g.(+), CD-P.g.(−) and CD-P.g.(+)). Histological and immunohistochemical examinations, measurement of serum lipopolysaccharide (LPS) levels and ELISA for cytokines in the liver were performed. We then studied the effects of LPS from P.g. (P.g.-LPS) on palmitate-induced steatotic hepatocytes in vitro, and performed immunohistochemical detection of P.g. in liver biopsy specimens of NASH patients.


Serum levels of LPS are upregulated in P.g.(+) groups. Steatosis of the liver developed in HFD groups, and foci of Mac2-positive macrophages were prominent in HFD-P.g.(+). P.g. was detected in Kupffer cells and hepatocytes. Interestingly, areas of fibrosis with proliferation of hepatic stellate cells and collagen formation were only observed in HFD-P.g.(+). In steatotic hepatocytes, expression of TLR2, one of the P.g.-LPS receptors, was upregulated. P.g.-LPS further increased mRNA levels of palmitate-induced inflammasome and proinflammatory cytokines in steatotic hepatocytes. We demonstrated for the first time that P.g. existed in the liver of NASH patients with advanced fibrosis.


Dental infection of P.g. may play an important role in NASH progression through upregulation of the P.g.-LPS-TLR2 pathway and activation of inflammasomes. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.


NASH Dental infection P. gingivalis Fibrosis TLRs 



Non-alcoholic fatty liver disease


Non-alcoholic steatohepatitis


Free fatty acid




Porphyromonas gingivalis


High fat diet


Chow diet


Hematoxylin and Eosin


α-smooth muscle actin


Toll-like receptor


Nod-like receptor 3





The authors thank Ryo Matsuda, Mao Muroi and Shinnichi Sakamoto for their support of this project. We are also grateful to Professor Kazuyuki Ishihara (Tokyo Dental College) for providing P.g.-specific polyclonal antibodies and Prof. Hidetoshi Tahara (Hiroshima University) for providing Hc3716-hTERT cells.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Hisako Furusho
    • 1
  • Mutsumi Miyauchi
    • 1
    Email author
  • Hideyuki Hyogo
    • 2
  • Toshihiro Inubushi
    • 1
  • Min Ao
    • 1
    • 3
  • Kazuhisa Ouhara
    • 4
  • Junzou Hisatune
    • 5
  • Hidemi Kurihara
    • 4
  • Motoyuki Sugai
    • 5
  • C. Nelson Hayes
    • 2
  • Takashi Nakahara
    • 2
  • Hiroshi Aikata
    • 2
  • Shoichi Takahashi
    • 2
  • Kazuaki Chayama
    • 2
  • Takashi Takata
    • 1
    Email author
  1. 1.Department of Oral and Maxillofacial Pathobiology, Basic Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of Medicine and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  3. 3.Department of Pediatric Dentistry, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  4. 4.Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  5. 5.Department of Bacteriology, Basic Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan

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