期刊论文详细信息
BMC Gastroenterology
Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease
Atsushi Nakajima7  Takashi Ooshima6  Takeshi Okanoue4  Atsuo Amano2  Yoshinori Kamisaki9  Kazuo Umemura3  Masae Kuboniwa2  Toshihide Shima4  Yoshio Sumida8  Iwai Tohnai1  Shogo Murata1  Masafumi Ono5  Kazuya Hokamura3  Ryota Nomura6  Kento Imajo7  Hironori Mawatari7  Hiroki Endo7  Koichiro Wada9  Kazuhiko Nakano6  Shuhei Naka6  Masato Yoneda7 
[1] Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan;Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan;Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan;Hepatology Center, Saiseikai Suita Hospital, Suita, Japan;Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan;Department of Pediatric Dentistry, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan;Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan;Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan
关键词: Insulin resistance;    Oral bacteria;    P. gingivalis;    Non-alcoholic steatohepatitis (NASH);    Non-alcoholic fatty liver disease (NAFLD);   
Others  :  1113140
DOI  :  10.1186/1471-230X-12-16
 received in 2011-08-05, accepted in 2012-02-16,  发布年份 2012
PDF
【 摘 要 】

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.

【 授权许可】

   
2012 Yoneda et al; BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150204013816981.pdf 694KB PDF download
Figure 4. 45KB Image download
Figure 3. 134KB Image download
Figure 2. 57KB Image download
Figure 1. 68KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Angulo P: Nonalcoholic fatty liver disease. N Engl J Med 2002, 18:1221-1231.
  • [2]Ludwig J, Viggiano TR, McGill DB, Oh BJ: Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980, 55:434-438.
  • [3]Liou I, Kowdley KV: Natural history of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006, 40:(Suppl 1):S11-S16.
  • [4]Diehl AM, Goodman Z, Ishak KG: Alcohol-like liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology 1998, 95:1056-1062.
  • [5]Abdelmalek MF, Diehl AM: Nonalcoholic fatty liver disease as a complication of insulin resistance. Med Clin North Am 2007, 91:1125-1149.
  • [6]Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al.: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003, 37:917-923.
  • [7]Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, et al.: Treatment of periodontitis and endothelial function. N Engl J Med 2007, 356:911-920.
  • [8]D'Aiuto F, Parkar M, Andreaou G, Brett PM, Ready D, Tonetti MS: Periodontitis and atherogenesis: causal association or simple coincidence? J Clin Periodontol 2004, 31:402-411.
  • [9]Sconyer JR, Crawford JJ, Moriarty JD: Relationship of bacteremia to tooth brushing in patients with periodontitis. J Am Dent Assoc 1973, 87:616-622.
  • [10]Caroll GC, Sebor RJ: Dental flossing and its relationship to transient bacteremia. J Periodontol 1980, 51:691-692.
  • [11]Forner L, Larsen T, Kilian M, Holmstrup P: Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin Periodontol 2006, 33:401-407.
  • [12]Scannapieco FA, Bush RB, Paju S: Associations between periodontal disease and risk for atherosclesosis, cardiovascular disease, and stroke. A systematic review. Ann Periodontol 2003, 8:38-53.
  • [13]Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S: Periodontal disease and cardiovascular disease. J Periodontol 1996, 67:1123-1137.
  • [14]Offenbacher S, Madianos PN, Champagne CM, Southerland JH, Paquette DW, Williams RC, et al.: Periodontitis-atherosclerosis syndrome: an expanded model of pathogenesis. J Periodontal Res 1999, 34:346-352.
  • [15]Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999, 116:1413-1419.
  • [16]Brunt EM: Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis 2001, 21:3-16.
  • [17]Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR: Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999, 94:2467-2474.
  • [18]Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M, et al.: Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatology 2009, 50:722-780.
  • [19]Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, et al.: Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT. Hepatology 2003, 37:1286-1292.
  • [20]Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, et al.: Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol 2007, 47:239-244.
  • [21]Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, et al.: Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 2008, 48:792-798.
  • [22]Matthews DR, Hosker JP, Rudenski AS: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28:412-419.
  • [23]Amano A, Nakagawa I, Kataoka K, Morisaki I, Hamada S: Distribution of Porphyromonas gingivalis strains with fimA genotypes in periodontitis patients. J Clin Microbiol 1999, 37:1426-1430.
  • [24]Tran SD, Rudney JD: Multiplex PCR using conserved and species-specific 16S rRNA gene primers for simultaneous detection of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. J Clin Microbiol 1996, 34:2674-2678.
  • [25]Nakagawa I, Amano A, Ohara-Nemoto Y, Endoh N, Morisaki I, Kimura S, et al.: Identification of a new variant of fimA gene of Porphyromonas gingivalis and its distribution in adults and disabled populations with periodontitis. J Periodontal Res 2002, 37:425-432.
  • [26]Nakagawa I, Amano A, Kimura RK, Nakamura T, Kawabata S, Hamada S: Disribution and molecular characterization of Porphyromonas gingivalis carrying a new type of fimA gene. J Clin Microbiol 2000, 38:1909-1914.
  • [27]Nakano K, Inaba H, Nomura R, Nemoto H, Takeda M, Yoshioka H, et al.: Detection of cariogenic Streptococcus mutans in extirpated heart valve and atheromatous plaque specimens. J Clin Microbiol 2006, 44:3313-3317.
  • [28]Nozaki Y, Fujita K, Yoneda M, Wada K, Shinohara Y, Takahashi H, et al.: Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease. J Hepatol 2009, 51:548-556.
  • [29]Barchetta I, Angelico F, Ben MD, Baroni MG, Pozzilli P, Morini S, et al.: Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med 2011, 9:85. BioMed Central Full Text
  • [30]Loe H: Periodontal disease: the sixth complication of diabetes mellitus. Diabetes Care 1993, 16:329-334.
  • [31]Nelson RG, Shlossman M, Budding L, Pettitt DJ, Saad MF, Genco RJ, et al.: Periodontal disease and NIDDM in Pima Indians. Diabetes Care 1990, 13:836-840.
  • [32]Ojima M, Takeda M, Yoshioka H, Nomura M, Tanaka N, Kato T, et al.: Relationship of periodontal bacterium genotypic variations with periodontitis in type 2 diabetic patients. Diabetes Care 2005, 28:433-434.
  • [33]Fujita K, Nozaki Y, Yoneda M, Wada K, Takahashi H, Kirikoshi H, et al.: Nitric oxide plays a crucial role in the development/progression of nonalcoholic steatohepatitis in the choline-deficient, l-amino acid-defined diet-fed rat model. Alcohol Clin Exp Res 2010, 34(Suppl 1):S18-24.
  • [34]Hoekstra M, Li Z, Kruijt JK, Van Eck M, Van Berkel TJC, Kuiper J: The expression level of non-alcoholic fatty liver disease-related gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status. J Hepatol 2010, 52:244-251.
  文献评价指标  
  下载次数:84次 浏览次数:33次