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

Nakahara, Takashi; Hyogo, Hideyuki; Ono, Atsushi; Nagaoki, Yuko; Kawaoka, Tomokazu; Miki, Daiki; Tsuge, Masataka; Hiraga, Nobuhiko; Hayes, Clair Nelson; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Aikata, Hiroshi; Ochi, Hidenori; Abe-Chayama, Hiromi; Furusho, Hisako; Shintani, Tomoaki; Kurihara, Hidemi; Miyauchi, Mutsumi; Takata, Takashi

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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 

Automatic Tags

Female; Male; Adult; Aged; Risk Factors; Disease Progression; Age Factors; Models, Biological; Mice; Fatty Acids; Biopsy; Middle Age; Diet -- Adverse Effects; Liver -- Metabolism; Liver -- Pathology; Nonalcoholic Fatty Liver Disease -- Metabolism; Nonalcoholic Fatty Liver Disease -- Microbiology; Nonalcoholic Fatty Liver Disease -- Pathology; Antibodies, Bacterial -- Blood; Arthritis Impact Measurement Scales; Gram-Negative Anaerobic Bacteria -- Immunology; Gram-Negative Bacterial Infections -- Complications; Gram-Negative Bacterial Infections -- Immunology; Gram-Negative Bacterial Infections -- Metabolism; Immunoglobulins -- Blood; Periodontitis -- Complications; Periodontitis -- Immunology; Periodontitis -- Metabolism

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