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

• DOI: 10.1007/s00535-017-1368-4
• Publication Date: 2017-07-24T02:51:01Z
• Authors: 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 Chayama
• Keywords: Adult; Male; 0303 health sciences; Biopsy; Fatty Acids; Age Factors; Middle Aged; Diet, High-Fat; Antibodies, Bacterial; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; Liver; Non-alcoholic Fatty Liver Disease; Immunoglobulin G; Bacteroidaceae Infections; Disease Progression; Animals; Humans; Female; Periodontitis; Aged

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.(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.(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.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.