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

Abstract

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

Porphyromonas gingivalis induced periodontitis exacerbates progression of non‐alcoholic steatohepatitis in rats

“…Yoneda et al . reported that the detection frequency of P. gingivalis in saliva from NASH patients was significantly higher than that in healthy subjects and that infection by P. gingivalis may be an additional risk factor for NASH (Yoneda et al, 2012). …”

“…A recent epidemiological study showing that P. gingivalis at high frequency was present in NAFLD/NASH patients suggested a close relationship between periodontitis and NASH (Yoneda et al, 2012). Furusho et al reported acceleration of hepatic inflammation and fibrosis as a result of P. gingivalis infection in the dental pulp of a maxillary molar in mice with fatty liver fed with high‐fat diet (HFD; Furusho et al, 2013).…”

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications

“…The normal gut microbiota carries out specific functions in host nutrient metabolism, xenobiotic and drug metabolism, structural integrity maintenance of the gut mucosal barrier, immunomodulation, and protection against pathogens 11, 12, 13, 14, 15. Recently, the gut microbiome has been shown to play a crucial role in health, as well as in diseases such as obesity,16 inflammatory bowel disease,17, 18 diabetes,19, 20 non‐alcoholic fatty liver disease,21, 22, 23 and several types of cancers 24, 25. Experimental evidence indicates that the human intestinal microbiome can influence tumor development and progression in the gastrointestinal tract by damaging DNA, activating oncogenic signaling pathways, producing tumor‐promoting metabolites, and suppressing the antitumor immune response 7, 25, 26, 27, 28, 29.…”

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

“…We emphasize that not only a specific strain of S. mutans but also other species could possibly induce aggravation of NASH. In fact, a specific strain of Porphyromonas gingivalis , one of the major periodontitis-related species, also aggravates NASH conditions in the same mouse model [19]. We will investigate the effects of other bacterial species to the development of NASH conditions in future studies.…”

“…All procedures used in the present study were approved by the Animal Care and Use Committee of the Osaka University Graduate School of Dentistry. The effects of intravenous administrations of S. mutans strains on the development of NASH were analysed using a NASH mouse model as previously described [15,19] with some modifications [17]. Briefly, 6-week-old C57BL/6J male mice ( n  = 94; Charles River Japan, Tokyo, Japan) were randomly divided into either the HFD plus phosphate-buffered saline (PBS) administration group ( n  = 42) or HFD plus TW871-treated group ( n  = 52).…”