Cell-surface Proteins of Streptococcus mutans Associated with Non-alcoholic Steatohepatitis Aggravation

Objectives: The associations of oral bacteria with systemic diseases have received attention, while infection with specific S. mutans strains was recently shown to be involved with development of non-alcoholic steatohepatitis (NASH). An approximately 190-kDa cell-surface protein antigen (PA) and 120-kDa Cnm protein are the major cell surface protein antigens of S. mutans. Here, we investigated the contributions of Cnm and PA to the mechanism of S. mutans-associated NASH aggravation in a mouse model.
Methods: All procedures were approved by the Animal Care and Use Committee of Osaka University Graduate School of Dentistry. S. mutans TW871 (k) and TW871PD, PA-defective isogenic mutants of TW871, and TW871CND, a Cnm-defective isogenic mutant of TW871 were used. C57BL/6J mice (6 weeks old) were fed a high fat diet for 4 weeks, then the test strains or phosphate-buffered saline (PBS) were intravenously administered. Mice were euthanized after 12 weeks and measurements of whole body, extirpated liver, and visceral fat weights, as well as histopathological evaluations of the liver specimens were performed. Serum levels of AST and ALT were also determined.
Results: Mice infected with TW871 showed significantly greater values for body and liver weights, and serum level of ALT than those administered TW871PD or TW871CND at 12 weeks after infection. Histopathological analyses revealed prominent infiltration of inflammatory cells and adipocellular deposition in livers extirpated 8 weeks after infection with TW871, while fibrosis was also observed in those extirpated after 12 weeks. In contrast, only slight inflammatory cell infiltration and adipocellular deposition were identified in livers extirpated even 12 weeks after infection with TW871PD or TW871CND.
Conclusions: These results suggest that both PA and Cnm of S. mutans are important cell surface structures associated with NASH development caused by S. mutans.
This study was supported by a Grant-in-Aid for Young Scientists (B) 25862010.