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Open Access Highly Accessed Research article

Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease

Masato Yoneda1, Shuhei Naka2, Kazuhiko Nakano2, Koichiro Wada103*, Hiroki Endo1, Hironori Mawatari1, Kento Imajo1, Ryota Nomura2, Kazuya Hokamura4, Masafumi Ono5, Shogo Murata6, Iwai Tohnai6, Yoshio Sumida7, Toshihide Shima8, Masae Kuboniwa9, Kazuo Umemura4, Yoshinori Kamisaki3, Atsuo Amano9, Takeshi Okanoue8, Takashi Ooshima2 and Atsushi Nakajima1

Author Affiliations

1 Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

2 Department of Pediatric Dentistry, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan

3 Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan

4 Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan

5 Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan

6 Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

7 Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan

8 Hepatology Center, Saiseikai Suita Hospital, Suita, Japan

9 Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan

10 Department of Pharmacology, Graduate School of Dentistry, Osaka University, 1-8 Yamada-oka, Suita, Osaka 565-0871, Japan

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BMC Gastroenterology 2012, 12:16  doi:10.1186/1471-230X-12-16

Published: 16 February 2012

Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis), a major causative agent of periodontitis.

Methods

The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH) and 48 with non-alcoholic fatty liver (NAFL) patients) and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis.

Results

The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16). In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91). Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%). Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT.

Conclusions

Infection with high-virulence P. gingivalis might be an additional risk factor for the development/progression of NAFLD/NASH.

Keywords:
Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic steatohepatitis (NASH); P. gingivalis; Oral bacteria; Insulin resistance