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Journal of Gastroenterology

, Volume 53, Issue 2, pp 269–280 | Cite as

Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease

  • Takashi Nakahara
  • Hideyuki Hyogo
  • Atsushi Ono
  • Yuko Nagaoki
  • Tomokazu Kawaoka
  • Daiki Miki
  • Masataka Tsuge
  • Nobuhiko Hiraga
  • Clair Nelson Hayes
  • Akira Hiramatsu
  • Michio Imamura
  • Yoshiiku Kawakami
  • Hiroshi Aikata
  • Hidenori Ochi
  • Hiromi Abe-Chayama
  • Hisako Furusho
  • Tomoaki Shintani
  • Hidemi Kurihara
  • Mutsumi Miyauchi
  • Takashi Takata
  • Koji Arihiro
  • Kazuaki ChayamaEmail author
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background and aims

The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH.

Methods

(1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE–TOFMS and LC–TOFMS.

Results

(1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(−) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(−) group (P < 0.05). Moreover, expression levels of SCD1 and ELOVL6 were significantly reduced.

Conclusions

These results suggest that P.g infection is an important risk factor for pathological progression in NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an important change that facilitates progression of NAFLD.

Keywords

Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Porphyromonas gingivalis Metabolome analysis Fatty acid 

Abbreviations

NAFLD

Nonalcoholic fatty liver disease

P.g

Porphyromonas gingivalis

ELISA

Enzyme-linked immunosorbent assay

CE–TOFMS

Capillary electrophoresis–time of flight mass spectrometry

LC–TOFMS

Liquid chromatography–time of flight mass spectrometry

NASH

Nonalcoholic steatohepatitis

LPS

Lipolysaccharide

SCD

Stearoyl-CoA desaturase

Elovl

Elongation of very long chain fatty acids

Notes

Author contributions

TN: study concept and design, data acquisition, data analysis and interpretation, generation of figures, preparation of manuscript. HH: data acquisition, study concept and design, literature search. AO: data acquisition. YN: data acquisition. TK: data acquisition. DM: data acquisition. MT: data acquisition. NH: data acquisition. CNH: preparation of manuscript. AH: data acquisition. MI: data acquisition. YK: data acquisition. HA: data acquisition. HO: data acquisition. HA-C: data acquisition. HF: data acquisition, literature search. TS: data acquisition. HK: data acquisition. MM: data acquisition. TT: study concept and design, data acquisition. KA: staining of human liver biopsy samples. KC: study concept and design, data acquisition, data analysis and interpretation.

Compliance with ethical standards

Financial support

This work was supported in part by a research grant of the Suzuken Memorial Foundation.

Conflict of interest

All authors have no conflict of interest related to this study.

Supplementary material

535_2017_1368_MOESM1_ESM.pdf (439 kb)
Supplemental Figure 1 Metabolites in the principle metabolic pathways of HFD or HFD and P.-infected mouse liver (PDF 439 kb)
535_2017_1368_MOESM2_ESM.docx (30 kb)
Supplementary material 2 (DOCX 30 kb)

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Copyright information

© Japanese Society of Gastroenterology 2017

Authors and Affiliations

  • Takashi Nakahara
    • 1
    • 9
  • Hideyuki Hyogo
    • 2
    • 9
  • Atsushi Ono
    • 1
    • 9
  • Yuko Nagaoki
    • 1
    • 9
  • Tomokazu Kawaoka
    • 1
    • 9
  • Daiki Miki
    • 3
    • 8
    • 9
  • Masataka Tsuge
    • 1
    • 9
  • Nobuhiko Hiraga
    • 1
    • 9
  • Clair Nelson Hayes
    • 1
    • 9
  • Akira Hiramatsu
    • 1
    • 9
  • Michio Imamura
    • 1
    • 9
  • Yoshiiku Kawakami
    • 1
    • 9
  • Hiroshi Aikata
    • 1
    • 9
  • Hidenori Ochi
    • 1
    • 8
    • 9
  • Hiromi Abe-Chayama
    • 9
    • 10
  • Hisako Furusho
    • 4
  • Tomoaki Shintani
    • 5
  • Hidemi Kurihara
    • 6
  • Mutsumi Miyauchi
    • 4
  • Takashi Takata
    • 4
  • Koji Arihiro
    • 7
  • Kazuaki Chayama
    • 1
    • 3
    • 8
    • 9
    Email author
  1. 1.Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research Graduate School of Biomedical Science, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of Gastroenterology and HepatologyJA Hiroshima General HospitalHiroshimaJapan
  3. 3.Laboratory for Digestive DiseasesRIKEN Center for Integrative Medical SciencesHiroshimaJapan
  4. 4.Department of Oral and Maxillofacial Pathobiology, Basic Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  5. 5.Center of Oral ExaminationHiroshima University HospitalHiroshimaJapan
  6. 6.Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  7. 7.Department of Anatomical PathologyHiroshima University HospitalHiroshimaJapan
  8. 8.Laboratory for Digestive DiseasesCenter for Genomic Medicine, RIKENHiroshimaJapan
  9. 9.Liver Research Project CenterHiroshima UniversityHiroshimaJapan
  10. 10.Center for Medical Specialist Graduate Education and Research, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan

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