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

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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.

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Most cited references 19

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Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.

J. Ludwig, T Viggiano, D McGill … (1980)

Nonalcoholic steatohepatitis is a poorly understood and hitherto unnamed liver disease that histologically mimics alcoholic hepatitis and that also may progress to cirrhosis. Described here are findings in 20 patients with nonalcoholic steatohepatitis of unknown cause. The biopsy specimens were characterized by the presence of striking fatty changes with evidence of lobular hepatitis, focal necroses with mixed inflammatory infiltrates, and, in most instances, Mallory bodies; Evidence of fibrosis was found in most specimens, and cirrhosis was diagnosed in biopsy tissue from three patients. The disease was more common in women. Most patients were moderately obese, and many had obesity-associated diseases, such as diabetes mellitus and cholelithiasis. Presence of hepatomegaly and mild abnormalities of liver function were common clinical findings. Currently, we know of no effective therapy.

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Periodontal disease. The sixth complication of diabetes mellitus.

H Löe (1993)

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Periodontal disease and cardiovascular disease.

R. Naranjo Garcia, G Heiss, S Offenbacher … (1996)

It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.

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Author and article information

Journal

Journal ID (nlm-ta): BMC Gastroenterol

Title: BMC Gastroenterology

Publisher: BioMed Central

ISSN (Electronic): 1471-230X

Publication date Collection: 2012

Publication date (Electronic): 16 February 2012

Volume: 12

Page: 16

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

Article

Publisher ID: 1471-230X-12-16

DOI: 10.1186/1471-230X-12-16

PMC ID: 3305584

PubMed ID: 22340817

SO-VID: 1e0644ce-5d74-4ccc-8165-27c0b0841ca7

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

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Abstract

Background

Methods

Results

Conclusions

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Karger: Gastroenterology

Most cited references 19

Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.

Periodontal disease. The sixth complication of diabetes mellitus.

Periodontal disease and cardiovascular disease.

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