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Relationship between Streptococcus mutans expressing Cnm in the oral cavity and non-alcoholic steatohepatitis: a pilot study
  1. Shuichi Tonomura1,
  2. Shuhei Naka2,
  3. Keiko Tabata2,
  4. Tasuku Hara3,
  5. Kojiro Mori4,
  6. Saiyu Tanaka4,
  7. Yoshio Sumida5,
  8. Kazuyuki Kanemasa4,
  9. Ryota Nomura6,
  10. Michiyo Matsumoto-Nakano2,
  11. Masafumi Ihara7,
  12. Nobuyuki Takahashi8,
  13. Kazuhiko Nakano6
  1. 1 Department of Neurology, Nara City Hospital, Nara, Japan
  2. 2 Department of Pediatric Dentistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan
  3. 3 Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  4. 4 Department of Gastroenterology and Hepatology, Nara City Hospital, Nara, Japan
  5. 5 Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi-gun, Japan
  6. 6 Department of Pediatric Dentistry, Division of Oral Infection and Disease Control, Osaka University School of Dentistry Graduate School of Dentistry, Suita, Japan
  7. 7 Department of Neurology, National Cerebral and Cardiovascular Center Hospital, Suita, Japan
  8. 8 Department of Neurology, Nara City Hospital, Nara, Japan
  1. Correspondence to Dr Shuichi Tonomura; tono0822shuichi{at}


Background Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host–microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD.

Methods This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD.

Results Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0–17.5) vs 20.0 (5.0–25.0), p=0.06; 5.1 (4.0–7.9) vs 4.4 (3.7–5.3), p=0.13, respectively).

Conclusions Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.

  • nonalcoholic steatohepatitis
  • infectious disease
  • bacterial infection

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  • Contributors Shuichi Tonomura, TH, KM, NT, Saiyu Tanaka, NT and YS participated in patient recruitment. Shuichi Tonomura and TH explained the study to patients, obtained written informed consent and collected oral samples. Shuichi Tonomura, SN, YS, KK, MI and NT designed the study. SN, KT and MM-N performed Streptococcus mutans detection and PCR. Shuichi Tonomura, SN and RN evaluated statistical analyses and drafted the manuscript. RN, MM-N, MI and KN interpreted the data and made substantial comments on the study. All authors approved the final draft submitted.

  • Funding This research was supported in part by a grant from the Smoking Research Foundation.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The protocol was approved by the ethical committee of Nara City Hospital, Nara, Japan (approval number: NCH 17–32).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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