Porphyromonas gingivalis induced periodontitis exacerbates progression of non‐alcoholic steatohepatitis in rats

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.

Histological effects and pharmacokinetics of lipopolysaccharide derived from Porphyromonas gingivalis on rat maxilla and liver concerning with progression into non‐alcoholic steatohepatitis

“…Previous epidemiologic and animal studies have reported that P. gingivalis , a primary periodontopathic bacterium, plays an important role in the relationship between periodontitis and NASH . We have demonstrated that experimental P. gingivalis periodontal infection led to NASH progression in rats with fatty liver . Although P. gingivalis was not observed in either the blood or liver, significant levels of endotoxin were detected in the blood.…”

“…Previous animal experiments showed that the intravenous injection and application of P. gingivalis via the dental pulp exacerbated steatohepatitis in HD fed mouse models. Further, we reported that a P. gingivalis infection model of periodontitis in HD rats induced the onset of NASH, and we also proposed that P. gingivalis as well as its LPS play an important role in the relationship between periodontitis and NASH …”

“…NAS was evaluated according to the criteria of Kleiner et al . as in the previous study . M: Total NAS in individual rats was calculated as the sum of three scores of steatosis, inflammation, and ballooning hepatocyte and is shown in terms of means and standard deviation of intra‐group scores.…”

Effects of theaflavins on tissue inflammation and bone resorption on experimental periodontitis in rats

“…Measurement conditions for micro‐CT were as follows: tube voltage, 65 kV; electrical current, 80 μA; image pixel size, 1024 × 1024; and slice thickness, 15 μm. After scanning, 3‐dimensional (3D) images were reconstructed using TRI/3D‐BON version 64 software (Ratoc System Engineering, Tokyo, Japan) in three regions (mesial, central, and distal sites) of the M1 (Figure A), the distance from the palatal cemento‐enamel junction (CEJ) to the alveolar bone crest (ABC) was measured as previously described . The average of the three distances was defined as the representative value for each rat.…”

“…After scanning, 3-dimensional (3D) images were reconstructed using TRI/3D-BON version 64 software (Ratoc System Engineering, Tokyo, Japan) in three regions (mesial, central, and distal sites) of the M1 (Figure 2A), the distance from the palatal cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) was measured as previously described. 32 The average of the three distances was defined as the representative value for each rat. The volumetric measurement of furcation was performed after the selection of a region of interest (ROI), which was selected according to the following standardized dimensions and anatomical landmarks: (a) a line 0.5 mm apical to the CEJ of the first molar as the coronal limit extended vertically 1 mm to the root apical, (b) a line 3 mm with the mesial-distal dimension from the mesial CEJ of the first molar, and (c) a line 2.5 mm with the buccal-palatal dimension ( Figure 2B).…”