Abstract
Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that can develop into hepatocirrhosis and hepatic carcinoma. In recent years, epidemiological and animal studies have reported that Porphyromonas gingivalis (P. gingivalis), a known periodontopathic bacteria, is closely related to NASH. However, previous studies could not demonstrate a direct relationship between periodontitis, P. gingivalis infection, and NASH. The purpose of the present study was to examine the impact of P. gingivalis-associated periodontitis on the onset and progression of NASH. Forty-two male Wistar rats were used in this study. Rats were fed a high-fat diet (HFD) for 12 weeks in order to induce fatty liver. At 4 weeks from the start of feeding, the animals were performed ligature placement around the maxillary first molar tooth in order to induce experimental periodontitis, and then a P. gingivalis slurry was applied around the ligature twice in a week for 8 weeks (HFD/Pg(+) group). Controls were given the slurry without P. gingivalis after ligature placement using the same protocol (HFD/Pg(-) group). Significant increases in alveolar bone resorption and inflammation in periodontal tissue around the molar tooth in the HFD/Pg(+) group were observed when compared with the HFD/Pg(-) group. Moreover, histological images showing NASH characterized by perivenular lipid deposition including big fatty drops, ballooning degeneration, and focal necrosis with inflammatory cells were confirmed in the liver of rats in the HFD/Pg(+) group. Significant increases in alanine aminotransaminase, aspartate aminotransferase, and C-reactive protein levels were observed in the HFD/Pg(+) group. Furthermore, endotoxin levels in serum in the HFD/Pg(+) group were significantly higher than those in the HFD/Pg(-) group. The present study demonstrated that experimental periodontitis induced by P. gingivalis led to the progression of NASH in rats with fatty liver. Increased levels of endotoxin derived from P. gingivalis infection appear to play a considerable role in the progression of NASH.