Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease

Nakahara, Takashi; Hyogo, Hideyuki; Ono, Atsushi; Nagaoki, Yuko; Kawaoka, Tomokazu; Miki, Daiki; Tsuge, Masataka; Hiraga, Nobuhiko; Hayes, C. Nelson; Hiramatsu, Akira; Kawakami, Yoshiiku; Ochi, Hidenori; Abe‐Chayama, Hiromi; Furusho, Hisako; Shintani, Tomoaki; Kurihara, Hidemi; Miyauchi, Mutsumi; Takata, Takashi; Arihiro, Koji; Chayama, Kazuaki

doi:10.1007/s00535-017-1368-4

Cited by 90 publications

(87 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… P. gingivalis IgA levels also predict myocardial infarction and stroke independently of established CVD risk factors . A significant correlation between fibrosis progression and P. gingivalis IgG titers has been reported in a study evaluating the effect of P. gingivalis infection as a risk factor in the progression of NASH . Our data are consistent with this finding, with significantly elevated IgG, IgM, and IgA levels in patients with severe AAH.…”

Section: Discussionsupporting

confidence: 91%

“…Intestinal dysbiosis has been observed by our group and others in experimental ALD/NAFLD in mice as well as humans . There are initial reports suggesting that the oral microbiome may also play a role in liver disease . In experimental animals, infection with P. gingivalis worsens steatohepatitis in mice fed a high‐fat diet .…”

Section: Discussionmentioning

confidence: 65%

“…Porphyromonas gingivalis is a major pathogen of severe PD. It functions as a keystone pathogen that not only sets the stage for the entire cascade of PD by altering the local immune microenvironment but also enters the blood circulation, is disseminated throughout the body, and contributes to multiple systemic diseases, such as diabetes, atherosclerosis, rheumatoid arthritis, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) . However, its role in ALD, particularly in AAH, is not clear.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Porphyromonas gingivalis as a Possible Risk Factor in the Development/Severity of Acute Alcoholic Hepatitis

et al. 2018

View full text Add to dashboard Cite

Bacterial infection is frequently observed in patients with alcoholic liver disease (ALD). We examined a possible role of Porphyromonas gingivalis in the development/progression and severity of disease in patients with acute alcoholic hepatitis (AAH). Plasma specimens from 47 patients with AAH (16 moderate, Model for End‐Stage Liver Disease [MELD] score <20]; 31 severe, MELD score >20) and 22 healthy controls (HCs) were collected. Clinical, drinking history (lifetime drinking history [LTDH]), and demographic data were collected. Antibody tests for immunoglobulin (Ig) G, IgM, and IgA against two P. gingivalis strains were performed. Between‐group comparisons and within‐group association analyses were carried out. Patients with severe AAH showed significantly higher plasma levels of IgG, IgA, and IgM against two P. gingivalis strains (W83 and 33277) compared to HCs. Patients with moderate AAH also had significantly elevated anti‐P. gingivalis IgA concentrations for both strains compared to HCs. Male patients with moderate AAH showed a significant inverse association in LTDH and anti‐P. gingivalis IgM. The aspartate aminotransferase:alanine aminotransferase ratio was positively associated with IgM of both strains in male patients with moderate AAH. Female patients with severe AAH showed a significant association between MELD scores and W83 IgM. Conclusion: Antibody response to P. gingivalis in AAH is elevated. Significantly elevated plasma anti‐P. gingivalis IgG, IgA, and IgM in severe AAH provide preliminary data that P. gingivalis could be a novel risk factor in the development/severity of AAH.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

See 1 more Smart Citation

Porphyromonas gingivalis as a Possible Risk Factor in the Development/Severity of Acute Alcoholic Hepatitis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Meanwhile, it is well established that periodontal infection, mainly P. gingivalis infection, contributes to the development and exacerbation of many systemic conditions, most of which are chronic inflammation (Beck & Offenbacher, 2005;Pizzo et al, 2010). P. gingivalis is detected in a higher frequency in patients with NASH than in non-NAFLD subjects (Nakahara et al, 2018;Yoneda et al, 2012). Evidence suggests that P. gingivalis infection can exacerbate steatohepatitis in animal model (Furusho et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…As a major prediabetic condition, IR can promote peripheral lipolysis that directly result in the conveyance of excessive free fatty acid to the liver (Mittendorfer, Magkos, Fabbrini, Mohammed, & Klein, ). Furthermore, in patients with NAFLD, P. gingivalis and the serum antibody against it were detected in a higher level than in non‐NAFLD subjects (Nakahara et al, ). It seems plausible that P. gingivalis may also contribute to the development of NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis‐derived lipopolysaccharide causes excessive hepatic lipid accumulation via activating NF‐κB and JNK signaling pathways

et al. 2019

View full text Add to dashboard Cite

Background Porphyromonas gingivalis is the main pathogen of periodontal disease affecting over half of the worldwide adult population. Recent studies have shown that P. gingivalis is related to the development of non‐alcoholic fatty liver disease (NAFLD), a global major chronic liver disease, especially in developed countries. However, how P. gingivalis contributes to the pathogenesis of NAFLD has not been fully clarified. We aimed to conduct a preliminary exploration of the underlying mechanism of P. gingivalis infection in the development of NAFLD. Methods Human hepatocellular cells HepG2 were incubated with/without oleic acid (OA) and tested for lipid accumulation upon stimulation by lipopolysaccharide (LPS) derived from P. gingivalis or Escherichia coli. Intracellular lipid droplet formation was analyzed and quantified by Oil Red O staining. The involvement of signaling pathway molecules and pro‐inflammatory cytokines related to NF‐κB and MAPKs were examined with Western blot and quantitative real‐time PCR (qRT‐PCR) analyses and further evaluated with inhibitor treatment and RNA interference. Results HepG2 cells accumulated more intracellular lipids when stimulated with P. gingivalis LPS, as compared to cells treated with E. coli LPS or control. Further pathway analysis demonstrated that after stimulation with P. gingivalis LPS, cells displayed significantly upregulated MyD88 expression, increased phosphorylation of p65 and JNK, and more release of pro‐inflammatory cytokines, such as IL‐1, IL‐8, and TNF‐α. In addition, suppression of phosphorylation of p65 and JNK by inhibitors and RNA interference resulted in a reduction in lipid accumulation upon P. gingivalis LPS treatment. Conclusions These results suggest that P. gingivalis‐derived LPS may contribute to intracellular lipid accumulation and inflammatory reaction of HepG2 cells via the activation of NF‐κB and JNK signaling pathways. This study offers a possible explanation to the functional involvement of P. gingivalis infection in the pathological progression of NAFLD. These findings may help design new treatment strategies in NAFLD.

show abstract

Infections at the nexus of metabolic-associated fatty liver disease

et al. 2021

View full text Add to dashboard Cite

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease that affects about a quarter of the world population. MAFLD encompasses different disease stadia ranging from isolated liver steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Although MAFLD is considered as the hepatic manifestation of the metabolic syndrome, multiple concomitant disease-potentiating factors can accelerate disease progression. Among these risk factors are diet, lifestyle, genetic traits, intake of steatogenic drugs, male gender and particular infections. Although infections often outweigh the development of fatty liver disease, pre-existing MAFLD could be triggered to progress towards more severe disease stadia. These combined disease cases might be underreported because of the high prevalence of both MAFLD and infectious diseases that can promote or exacerbate fatty liver disease development. In this review, we portray the molecular and cellular mechanisms by which the most relevant viral, bacterial and parasitic infections influence the progression of fatty liver disease and steatohepatitis. We focus in particular on how infectious diseases, including coronavirus disease-19, hepatitis C, acquired immunodeficiency syndrome, peptic ulcer and periodontitis, exacerbate MAFLD. We specifically underscore the synergistic effects of these infections with other MAFLD-promoting factors. Keywords Metabolic-associated fatty liver disease (MAFLD) • Non-alcoholic steatohepatitis (NASH) • Infectious diseases • Lipid metabolism • Liver • SARS-CoV-2 • Human immunodeficiency virus • Hepatitis C • Helicobacter pylori • Klebsiella pneumoniae

show abstract

Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease

Abstract: These results suggest that P.g infection is an important risk factor for pathological progression in NAFLD. Increase in the monounsaturated/saturated fatty acid ratio may be an important change that facilitates progression of NAFLD.

Cited by 90 publications

References 38 publications

Porphyromonas gingivalis as a Possible Risk Factor in the Development/Severity of Acute Alcoholic Hepatitis

Porphyromonas gingivalis as a Possible Risk Factor in the Development/Severity of Acute Alcoholic Hepatitis

Porphyromonas gingivalis‐derived lipopolysaccharide causes excessive hepatic lipid accumulation via activating NF‐κB and JNK signaling pathways

Infections at the nexus of metabolic-associated fatty liver disease

Contact Info

Product

Resources

About