Takashi Nakahara1,2, Hideyuki Hyogo3,2, Atsushi Ono1,2, Yuko Nagaoki1,2, Tomokazu Kawaoka1,2, Daiki Miki4,5,2, Masataka Tsuge1,2, Nobuhiko Hiraga1,2, Clair Nelson Hayes1,2, Akira Hiramatsu1,2, Michio Imamura1,2, Yoshiiku Kawakami1,2, Hiroshi Aikata1,2, Hidenori Ochi1,5,2, Hiromi Abe-Chayama2,6, Hisako Furusho7, Tomoaki Shintani8, Hidemi Kurihara9, Mutsumi Miyauchi7, Takashi Takata7, Koji Arihiro10, Kazuaki Chayama11,12,13,14. 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 Sciences, Hiroshima University, Hiroshima, Japan. 2. Liver Research Project Center, Hiroshima University, Hiroshima, Japan. 3. Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hiroshima, Japan. 4. Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan. 5. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan. 6. Center for Medical Specialist Graduate Education and Research, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 7. Department of Oral and Maxillofacial Pathobiology, Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 8. Center of Oral Examination, Hiroshima University Hospital, Hiroshima, Japan. 9. Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. 10. Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan. 11. 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 Sciences, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp. 12. Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan. chayama@hiroshima-u.ac.jp. 13. Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan. chayama@hiroshima-u.ac.jp. 14. Liver Research Project Center, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
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.
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.ginfection 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.ginfection 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.
Authors: Elena Figuero; María Sánchez-Beltrán; Susana Cuesta-Frechoso; Jose María Tejerina; Jose Antonio del Castro; Jose María Gutiérrez; David Herrera; Mariano Sanz Journal: J Periodontol Date: 2011-03-29 Impact factor: 6.993
Authors: K Nakano; H Inaba; R Nomura; H Nemoto; H Takeuchi; H Yoshioka; K Toda; K Taniguchi; A Amano; T Ooshima Journal: Oral Microbiol Immunol Date: 2008-04
Authors: H Nishi; N Hosomi; K Ohta; S Aoki; M Nakamori; T Nezu; H Shigeishi; T Shintani; T Obayashi; K Ishikawa; N Kinoshita; Y Shiga; M Sugiyama; H Ohge; H Maruyama; H Kawaguchi; H Kurihara Journal: Clin Exp Immunol Date: 2020-03-24 Impact factor: 4.330