Longitudinal comparison of Streptococcus mutans-induced aggravation of non-alcoholic steatohepatitis in mice

Abstract

Background: We previously reported that intravenous administration of Streptococcus mutans strain TW871 caused typical non-alcoholic steatohepatitis (NASH)-like findings in a high-fat diet (HFD) mouse model at 16 weeks after initiating the experiment. Objective: The purpose of the present study was to analyse mice administered S. mutans TW871 fed a HFD for various periods of time. Methods: First, 6-week-old C57BL/6J mice were fed an HFD for 4 weeks, then TW871 (1 × 107 CFU) or phosphate-buffered saline (PBS) were intravenously administered. Mice were euthanized 12, 16, 20, and 48 weeks after starting the experiment, and conventional clinical and histopathological evaluations were performed. Results: Typical NASH-like findings were not identified in the mice at 12 weeks, while they were observed in the TW871 group at 16 weeks, and the severity of NASH symptoms were increased at 20 weeks. Furthermore, signs of severe NASH were also observed at 48 weeks. In contrast, in the PBS-administered group, the NASH findings were identified only at 48 weeks and no typical NASH features were observed at 12, 16, or 20 weeks. Conclusion: These results suggest that intravenous administration of a specific S. mutans strain aggravates NASH in a time-dependent manner in the mice in contrast to mice without S. mutans exposure.

Relationship betweenStreptococcus mutansexpressing Cnm in the oral cavity and non-alcoholic steatohepatitis: a pilot study

“…However, it remains unknown whether this finding is consistent with previous animal studies. In animal models, intravenous administration of cnm -positive S. mutans was shown to accumulate in the liver and aggregated NASH,11 12 while we detected cnm -positive S. mutans in oral cavities, not in the blood. To explain this contradiction, it is necessary to introduce the unique host–pathogen interaction in the periodontal crevice and evaluate the bacterial properties of S. mutans .…”

“…Focusing on the specific strain Streptococcus mutans , which is one of the major causative pathogens of dental caries, we suggested the role of this bacterium in development of systemic diseases including inflammatory bowel disease,7 immunoglobulin A nephropathy,8 and intracerebral haemorrhage 9 10. Moreover, we identified the contribution of cnm gene-positive S. mutans expressing the collagen-binding protein, Cnm, on the cell surface ( cnm -positive S. mutans ), to the aggravation of NASH in obesity model mice 11 12. However, in humans, the relationship between NASH and oral hygiene, with a focus on cnm -positive S. mutans infection, remains unknown.…”

The association between missing teeth and non‐alcoholic fatty liver disease in adults

“…In another study with rats, the microvesicular steatosis in the liver caused by periodontitis is reversible after removal of the ligature (Dos Santos Carvalho et al., ). Meanwhile, recent studies showed that S. mutans , a major dental caries pathogen, could induce non‐alcoholic steatohepatitis (NASH) in a mouse model (Naka et al., , ).…”

“…It is generally considered to be the major bacteria responsible for dental caries, which is another major cause for the tooth loss (Richards et al., ). Evidence from both human and animal studies have indicated the possible associations between S. mutans and systemic diseases such as infective endocarditis (Moreillon & Que, ), atheromatous plaque specimens (Nakano et al., ), as well as NASH (Naka et al., , ). Therefore, the association between tooth loss and NAFLD may reflect the detrimental impact of S. mutans on both oral and systemic health.…”

“…Streptococcus mutans is occasionally isolated from extra‐oral sites, which implies potential associations with several kinds of systemic diseases, such as atheromatous plaque specimens (Nakano et al., ) and cardiovascular specimens (Nakano et al., ). In addition, recent animal studies found that a specific strain of S. mutans could induce NAFLD in mice (Naka et al., , ). Moreover, recent studies have also reported that ectopic colonization of oral bacteria in the intestine is linked to inflammatory diseases (Atarashi et al., ; Cao, ) and gut–liver axis malfunction (Han, Sun, & Yang, ).…”