New paradigm in the relationship between periodontal disease and systemic diseases

Yamazaki, Kazuhisa

doi:10.1002/9781118982907.ch15

Cited by 5 publications

(8 citation statements)

References 127 publications

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“…A second hypothesis suggests that various proinflammatory cytokines are produced in inflamed periodontal tissue and can enter systemic circulation. However, each hypothesis suffers from contradictory arguments, which preclude them from universal acceptance …”

Section: Discussionmentioning

confidence: 99%

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An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ‐free mice

Sato

Yokoji

Yamada

et al. 2018

J of Periodontal Research

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Section: Discussionmentioning

confidence: 99%

“…However, each hypothesis suffers from contradictory arguments, which preclude them from universal acceptance. 18 We have recently shown that oral administration of P. gingivalis induces dysbiosis, impairment of gut barrier function, endotoxemia and metabolic changes in the composition of gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ‐free mice

Sato

Yokoji

Yamada

et al. 2018

J of Periodontal Research

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“…Periodontal disease is a chronic inflammatory disease caused by a complex interaction between oral pathobionts and host defense mechanisms (6) that affects tooth-supporting structures, leading to tooth loss if left untreated. Accumulating evidence strongly suggests that periodontal disease not only destroys the periodontium, but also increases the risk of various non-oral diseases including metabolic disorders such as NAFLD (7). Epidemiological studies have demonstrated a significant association between clinical and/or microbial periodontal parameters and NAFLD (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice

et al. 2021

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Background & AimsPeriodontitis increases the risk of nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms are unclear. Here, we show that gut dysbiosis induced by oral administration of Porphyromonas gingivalis, a representative periodontopathic bacterium, is involved in the aggravation of NAFLD pathology.MethodsC57BL/6N mice were administered either vehicle, P. gingivalis, or Prevotella intermedia, another periodontopathic bacterium with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, l-amino acid-defined, high-fat diet with 60 kcal% fat and 0.1% methionine (CDAHFD60). The gut microbial communities were analyzed by pyrosequencing the 16S ribosomal RNA genes. Metagenomic analysis was used to determine the relative abundance of the Kyoto Encyclopedia of Genes and Genomes pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance-based metabolomics coupled with multivariate statistical analyses. Hepatic gene expression profiles were analyzed via DNA microarray and quantitative polymerase chain reaction.ResultsCDAHFD60 feeding induced hepatic steatosis, and in combination with bacterial administration, it further aggravated NAFLD pathology, thereby increasing fibrosis. Gene expression analysis of liver samples revealed that genes involved in NAFLD pathology were perturbed, and the two bacteria induced distinct expression profiles. This might be due to quantitative and qualitative differences in the influx of bacterial products in the gut because the serum endotoxin levels, compositions of the gut microbiota, and serum metabolite profiles induced by the ingested P. intermedia and P. gingivalis were different.ConclusionsSwallowed periodontopathic bacteria aggravate NAFLD pathology, likely due to dysregulation of gene expression by inducing gut dysbiosis and subsequent influx of gut bacteria and/or bacterial products.

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“…There is an increasing amount of evidence suggesting that periodontal disease is associated with an increased risk of various metabolic, inflammatory, and autoimmune diseases, such as type 2 diabetes, atherosclerotic vascular diseases, and rheumatoid arthritis ( 1 ). Periodontal disease is a chronic inflammatory condition of the periodontium, which is induced by periodontopathic bacteria, such as Porphyromonas gingivalis .…”

Section: Introductionmentioning

confidence: 99%

“…Given these pathological features, bacteremia, endotoxemia, and the invasion of locally produced proinflammatory cytokines into the systemic circulation have been considered the causal mechanisms by which periodontal disease increases the risk of systemic diseases ( 1 ). Consistently with this hypothesis, a number of studies have demonstrated the presence of periodontopathic bacterial DNA in various tissues and organs ( 4 – 6 ) and an elevated level of proinflammatory cytokines, in particular IL-6, in the blood ( 7 – 9 ).…”

Section: Introductionmentioning

confidence: 99%

Oral Administration of Porphyromonas gingivalis Alters the Gut Microbiome and Serum Metabolome

Kato

Yamazaki

Nakajima

et al. 2018

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Increasing evidence suggest that alterations of the gut microbiome underlie metabolic disease pathology by modulating gut metabolite profiles. We have shown that orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, alters the gut microbiome; that may be a novel mechanism by which periodontitis increases the risk of various diseases. Given the association between periodontal disease and metabolic diseases, it is possible that P. gingivalis can affect the metabolites. Metabolite profiling analysis demonstrated that several amino acids related to a risk of developing diabetes and obesity were elevated in P. gingivalis-administered mice. Our results revealed that the increased risk of various diseases by P. gingivalis might be mediated at least in part by alteration of metabolic profiles. The findings should add new insights into potential links between periodontal disease and systemic disease for investigators in periodontal disease and also for investigators in the field of other diseases, such as metabolic diseases.

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New paradigm in the relationship between periodontal disease and systemic diseases

Cited by 5 publications

References 127 publications

An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ‐free mice

An orally administered oral pathobiont and commensal have comparable and innocuous systemic effects in germ‐free mice

Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice

Oral Administration of Porphyromonas gingivalis Alters the Gut Microbiome and Serum Metabolome

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