Dental infection of Porphyromonas gingivalis induces progression of non-alcoholic steatohepatitis

Objective:Non-alcoholic steatohepatitis (NASH) is a major form of liver disease in metabolic syndrome patients. Recently, it is accepted that gut-derived bacterial products play a central role in NASH progression. Although an infection of Porphyromonas.gingivalis (P.g.), an important periodontal pathogens, has been found to be systemic diseases such as cardiovascular disease and diabetes mellitus, the relationship between P.g. and NASH is still uncertain. In the present study, we investigated effects of dental infection with P.g. on progression of NASH. Method:Twelve C57BL/6J mice (5 weeks-old) were fed with high fat diet (HF) to evoke steatosis. Another 12 mice fed with normal diet (ND) were used as control. After 12 weeks, P. g. was infected in coronal pulp of upper first molar of 6 animals in each group (P.g.+HF and P.g.+ND). Result: After 6 weeks, periapical granuloma was developed and serum concentration of LPS was raised in P.g.+HF and P.g.+ND groups. In the liver of HF groups, prominent accumulation of lipid droplets occurred. Although the foci of macrophages were observed in both P.g+ND and P.g.-HF, number of the foci markedly increased in P.g.+HF. Interestingly, area of fibrosis only existed in P.g.+HF. Immunohistochemical staining showed numerous positive reaction to P.g. in pulp and macrophages and neutrophils in periapical granuloma. In the liver tissue, immunolocalization of P.g. was detected not only in Kupffer cells but also in hepatocytes and endothelial cells. In vitro studies using a human hepatocyte cell line showed that palminate-pretreatment remarkably upregulated P.g.-LPS induced mRNA levels for inflamazome like NLRP3 and caspase-1 and proinflammatory cytokines like IL-1b, IL-6, and TNF-á. Conclusion:These results indicate that the dental infection of P.g. can caused liver injury though the upregulation of cytokine production. We suggest that P.g. may play an important role in pathogenic mechanism of NASH progression.