Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice

Furusho, Hisako; Miyauchi, Mutsumi; Hyogo, Hideyuki; Inubushi, Toshihiro; Ao, Min; Ouhara, Kazuhisa; Hisatune, Junzou; Kurihara, Hidemi; Sugai, Motoyuki; Hayes, C. Nelson; Nakahara, Takashi; Aikata, Hiroshi; Takahashi, Shoichi; Chayama, Kazuaki; Takata, Takashi

doi:10.1007/s00535-012-0738-1

Cited by 117 publications

(170 citation statements)

References 41 publications

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“…Recently, it was reported that P.g. was detected in the livers of patients with non-alcoholic fatty liver disease (NAFLD), including non-alcholic fatty liver and nonalcholic steatohepatitis (NASH) [15,28]. In NAFLD, excessive delivery of free fatty acids and imbalance in lipid synthesis cause increased fat accumulation in the liver.…”

Section: Discussionmentioning

confidence: 99%

Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway

Ishikawa

Yoshida

Okamura

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

100

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Periodontal diseases are common chronic inflammatory disorders that result in the destruction of tissues around teeth. Many clinical studies suggest that periodontal diseases are risk factors for insulin resistance and diabetic mellitus development. However, the molecular mechanisms by which periodontal diseases regulate the progress of diabetes mellitus remain unknown. In this study, we investigated whether Porphyromonas gingivalis (P.g.), a major pathogen of periodontal diseases, present in the oral cavity, moves to the liver and affects hepatic glycogen synthesis. SNAP26b-tagged P.g. (SNAP-P.g.) was introduced into the oral cavity to induce periodontal disease in 4-week old female Balb/c mice. SNAP-P.g. was detected in the liver extracted from SNAP-P.g.-treated mice using nested PCR analysis. High blood glucose levels tended to promote SNAP-P.g. translocation from the oral cavity to the liver in mice. Periodic acid-Schiff staining suggested that hepatic glycogen synthesis decreased in SNAP-P.g.-treated mice. SNAP-P.g. was also internalized into the human hepatoma cell line HepG2, and this attenuated the phosphorylation of insulin receptor substrate (IRS)-1, Akt and glycogen synthase kinase-3β induced by insulin. Insulin-induced glycogen synthesis was suppressed by SNAP-P.g. in HepG2 cells. Our results suggest that P.g. translocation from the oral cavity to the liver may contribute to the progress of diabetes mellitus by influencing hepatic glycogenesis.

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Section: Discussionmentioning

confidence: 99%

Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway

Ishikawa

Yoshida

Okamura

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

100

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“…Previous animal experiments showed that intravenous injection (Yoneda et al, 2012) and direct application via dental pulp (Furusho et al, 2013) of P. gingivalis exacerbated steatohepatitis in murine models fed HFD. However, the results in these experiments were not related to periodontitis induced by P. gingivalis infection.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Furusho et al reported that when P. gingivalis was administered into the pulp chamber in steatosis model mice fed HFD, hepatic lipid deposition and focal fibrosis developed in mice with periapical lesions, as compared to control animals without P. gingivalis infection (Furusho et al, 2013). These observations largely agree with our results using experimental periodontitis.…”

Section: Discussionmentioning

confidence: 99%

“…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). …”

Section: Introductionmentioning

confidence: 99%

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

Kuraji

Fujita

et al. 2016

Clinical & Exp Dental Res

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Non‐alcoholic steatohepatitis (NASH) is a chronic liver disease that can develop into hepatocirrhosis and hepatic carcinoma. In recent years, epidemiological and animal studies have reported that Porphyromonas gingivalis (P. gingivalis), a known periodontopathic bacteria, is closely related to NASH. However, previous studies could not demonstrate a direct relationship between periodontitis, P. gingivalis infection, and NASH. The purpose of the present study was to examine the impact of P. gingivalis‐associated periodontitis on the onset and progression of NASH. Forty‐two male Wistar rats were used in this study. Rats were fed a high‐fat diet (HFD) for 12 weeks in order to induce fatty liver. At 4 weeks from the start of feeding, the animals were performed ligature placement around the maxillary first molar tooth in order to induce experimental periodontitis, and then a P. gingivalis slurry was applied around the ligature twice in a week for 8 weeks (HFD/Pg(+) group). Controls were given the slurry without P. gingivalis after ligature placement using the same protocol (HFD/Pg(−) group). Significant increases in alveolar bone resorption and inflammation in periodontal tissue around the molar tooth in the HFD/Pg(+) group were observed when compared with the HFD/Pg(−) group. Moreover, histological images showing NASH characterized by perivenular lipid deposition including big fatty drops, ballooning degeneration, and focal necrosis with inflammatory cells were confirmed in the liver of rats in the HFD/Pg(+) group. Significant increases in alanine aminotransaminase, aspartate aminotransferase, and C‐reactive protein levels were observed in the HFD/Pg(+) group. Furthermore, endotoxin levels in serum in the HFD/Pg(+) group were significantly higher than those in the HFD/Pg(−) group. The present study demonstrated that experimental periodontitis induced by P. gingivalis led to the progression of NASH in rats with fatty liver. Increased levels of endotoxin derived from P. gingivalis infection appear to play a considerable role in the progression of NASH.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Baba

Iwatsuki

Yoshida

et al. 2017

Annals of Gastroent Surgery

101

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Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum, which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro‐ and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

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Dental infection of Porphyromonas gingivalis exacerbates high fat diet-induced steatohepatitis in mice

Abstract: Dental infection of P.g. may play an important role in NASH progression through upregulation of the P.g.-LPS-TLR2 pathway and activation of inflammasomes. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.

Cited by 117 publications

References 41 publications

Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway

Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway

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

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

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