Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease
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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.
(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.
KeywordsNon-alcoholic fatty liver disease Non-alcoholic steatohepatitis Porphyromonas gingivalis Metabolome analysis Fatty acid
Nonalcoholic fatty liver disease
Enzyme-linked immunosorbent assay
Capillary electrophoresis–time of flight mass spectrometry
Liquid chromatography–time of flight mass spectrometry
Elongation of very long chain fatty acids
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
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.