Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities

Nat Rev Immunol. 2021 Jul;21(7):426-440. doi: 10.1038/s41577-020-00488-6. Epub 2021 Jan 28.


Periodontitis, a major inflammatory disease of the oral mucosa, is epidemiologically associated with other chronic inflammation-driven disorders, including cardio-metabolic, neurodegenerative and autoimmune diseases and cancer. Emerging evidence from interventional studies indicates that local treatment of periodontitis ameliorates surrogate markers of comorbid conditions. The potential causal link between periodontitis and its comorbidities is further strengthened by recent experimental animal studies establishing biologically plausible and clinically consistent mechanisms whereby periodontitis could initiate or aggravate a comorbid condition. This multi-faceted 'mechanistic causality' aspect of the link between periodontitis and comorbidities is the focus of this Review. Understanding how certain extra-oral pathologies are affected by disseminated periodontal pathogens and periodontitis-associated systemic inflammation, including adaptation of bone marrow haematopoietic progenitors, may provide new therapeutic options to reduce the risk of periodontitis-associated comorbidities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / immunology
  • Alzheimer Disease / microbiology
  • Animals
  • Bone Marrow / immunology
  • Causality
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / microbiology
  • Comorbidity
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Inflammation / epidemiology*
  • Inflammation / immunology
  • Inflammatory Bowel Diseases / epidemiology
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / microbiology
  • Models, Biological
  • Mouth / microbiology
  • Periodontal Diseases / epidemiology*
  • Periodontal Diseases / immunology
  • Periodontal Diseases / microbiology
  • Periodontitis / epidemiology
  • Periodontitis / immunology
  • Periodontitis / microbiology
  • Risk Factors