Analysis of pathogenesis-related factors of Streptococcus mutans from the oral cavity of patients with nonalcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL), which rarely progresses, and non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. Previous studies have shown that Streptococcus mutans positive for collagen-binding protein (Cnm) and the 190-kDa cell surface protein antigen (PA) may be involved in NASH progression. In this study, we analyzed saliva samples obtained from patients with NAFL and NASH, and investigated the involvement of these proteins in NASH development by administrating clinical isolates to a mouse model. There was no significant difference in the detection rate of S. mutans between the NAFL and NASH patient groups; however, Cnm+/PA+ S. mutans strains were more frequently detected in patients with NASH. Furthermore, patients with NASH with Cnm+/PA+ S. mutans showed significantly higher levels of type IV collagen 7S, a biomarker of liver fibrosis, compared to patients with NASH without these strains. Adiponectin, an anti-inflammatory cytokine mainly secreted by adipocytes, was significantly lower. The collagen-binding ability of Cnm+/PA+ S. mutans strains was significantly higher than that of other S. mutans strains without both proteins. Cnm+/PA+ S. mutans showed significantly higher binding ability to type IV collagen than to type I collagen. RT-qPCR analysis revealed that pac expression was significantly higher in Cnm+/PA+ S. mutans isolated from the NASH group. Administration of Cnm+/PA+ S. mutans into a NASH mouse model via the jugular vein caused NASH-like pathology in mouse liver tissues. These results suggest that Cnm+/PA+ S. mutans is associated with NASH aggravation.