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Periodontitis: from microbial immune subversion to systemic inflammation
Open accessAbstract
Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities that can mediate inflammatory pathology at local as well as distant sites. This Review discusses the mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extra-oral sites.
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“Recent studies have also highlighted that the mineralized structure of calculus may promote a dysbiotic shift in the microbial community, contributing to persistent inflammation and disease progression [4].”
From In vitro biomimetic development of artificial dental calculus: a proof of concept study (2025) · cites this paper as [4]
In the citing paper
“Periodontal disease is caused by dysbiosis of subgingival microbial communities that adversely affects the host immune system such that it creates and maintains unmitigated inflammation in gingival and periodontal tissues, thus preventing immune subversion and tissue recovery.10”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [10]
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“It is speculated that aspiration pneumonia is also closely related to oral microorganisms due to the aspiration of oropharyngeal secretions (Hajishengallis, 2015).”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Hajishengallis, 2015
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The Role of Neutrophil Extracellular Traps in Periodontitis
Wang, J., Zhou, Y., Ren, B., Zou, L., He, B., & Li, M. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.639144 · Cited by 79
“Characterized by progressive loss of attachments and alveolar bone, which eventually leads to tooth loss, periodontitis also has adverse impacts on the appearance, mastication, and systemic health (Hajishengallis, 2015).”
BackgroundGrant, M. M., Taylor, J. J., Jaedicke, K. M., Creese, A. J., Gowland, C., Burke, B., Doudin, K., Patel, U. S., Weston, P., Milward, M. R., et al. (2022) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.13630 · Cited by 75
“The pathophysiology of periodontitis involves a dysfunctional immuneinflammatory response to a dysbiosis that starts within the dental plaque biofilm (Hajishengallis, 2015), and which then propagates an exaggerated and destructive inflammatory milieu, underpinned by certain genetic and lifestyle risk exposures such as…”
BackgroundThe role of vitamin D in periodontal health and disease
Lu, E. M. (2022) · Journal of Periodontal Research · doi:10.1111/jre.13083 · Cited by 75
Li, J., Wang, Y., Tang, M., Zhang, C., Fei, Y., Li, M., Li, M., Gui, S., & Guo, J. X. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-02261-y · Cited by 80
“In addition, there is growing clinical evidence that periodontitis places a huge burden on the public health care system due to the close links to other diseases such as diabetes, Alzheimer’s disease, rheumatoid arthritis, colitis and even cancer [5–7].”
BackgroundNatural and induced immune responses in oral cavity and saliva
Matsuoka, M., Soria, S. A., Pires, J. R., Sant’Ana, A. C. P., & Freire, M. (2025) · BMC Immunology · doi:10.1186/s12865-025-00713-8 · Cited by 91
“P. gingivalis , for example, has the ability to modulate the host’s immune response, subvert-ing defense mechanisms to favor its own survival and contributing to chronic inflammation [211, 212].”
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Dinakaran, V., Mandape, S. N., Shuba, K., Pratap, S., Sakhare, S. S., Tabatabai, M., Smoot, D. T., Farmer‐Dixon, C. M., Kesavalu, L. N., Adunyah, S. E., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.03220 · Cited by 75
From Beyond the Pale to the Pale Riders: The Emerging Association of Bacteria with Oral Cancer
Fitzsimonds, Z. R., Hernandez, C. J. R., Bagaitkar, J., & Lamont, R. J. (2020) · Journal of Dental Research · doi:10.1177/0022034520907341 · Cited by 80
“Importantly, periodontal bacterial communities are pathogenic only in a susceptible host (Hajishengallis 2015).”
BackgroundInflammation of the periodontium associates with risk of future cardiovascular events
Dyke, T. E. V., Kholy, K. E., Ishai, A., Takx, R. A. P., Mezue, K. N., Abohashem, S., Ali, A., Yuan, N., Hsue, P. Y., Osborne, M. T., et al. (2021) · Journal of Periodontology · doi:10.1002/jper.19-0441 · Cited by 78
Probiotic Species in the Management of Periodontal Diseases: An Overview
Zhang, Y., Ding, Y., & Guo, Q. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.806463 · Cited by 80
“In fact, subversion of host immunity by dysbiotic periodontal microbiota not only gives rise to periodontal diseases but also contributes to systemic inflammation (Hajishengallis, 2015).”
BackgroundModeling Crevicular Fluid Flow and Host‐Oral Microbiome Interactions in a Gingival Crevice‐on‐Chip
Makkar, H., Zhou, Y., Tan, K. S., Lim, C. T., & Sriram, G. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202202376 · Cited by 77
Biosensor and Lab-on-a-chip Biomarker-identifying Technologies for Oral and Periodontal Diseases
Steigmann, L., Maekawa, S., Sima, C., Travan, S., Wang, C.-W., & Giannobile, W. V. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.588480 · Cited by 77
“F. nucleatum is an early colonizer that bridges the pathogens and thus identified as an emerging opportunistic pathogen that plays a critical role in the dysbiosis of microbiome (Hajishengallis, 2015).”
BackgroundComplement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches
Hajishengallis, G., Maekawa, T., Abe, T., Hajishengallis, E., & Lambris, J. D. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-18603-0_4 · Cited by 73
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Engineered Bdellovibrio bacteriovorus: A countermeasure for biofilm-induced periodontitis
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Kim, P. D., Xia, X., Crump, K. E., Abe, T., Hajishengallis, G., & Sahingur, S. E. (2015) · Infection and Immunity · doi:10.1128/iai.00424-15 · Cited by 69
Self-citationLipopolysaccharide, a possible molecular mediator between periodontitis and coronary artery disease
Liljestrand, J. M., Paju, S., Buhlin, K., Persson, G. R., Sarna, S. J., Nieminen, M. S., Sinisalo, J. P., Mäntylä, P., & Pussinen, P. J. (2017) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12751 · Cited by 71
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Shi, E., Bai, L., Mao, L., Wang, H., Yang, X., Wang, Y., Zhang, M., Li, C., & Wang, Y. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-01114-w · Cited by 72
“In addition, periodontal disease is reported to be related to some systemic diseases, such as arteriosclerosis, diabetes, aspiration pneumonia and vascular disease [4].”
BackgroundAdvances of exosomes in periodontitis treatment
Lin, H., Chen, H., Zhao, X., Ding, T., Wang, Y., Chen, Z. B., Tian, Y., Zhang, P., & Shen, Y. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03487-4 · Cited by 74
“Background Periodontitis is an inflammatory disease initiated by dysbiosis of the local microbial community and is characterized by the relative abundance or influence imbalance of microbial species [1].”
BackgroundThe Role of the Microbiome in the Etiopathogenesis of Colon Cancer
Tekle, G. E., Andreeva, N., & Garrett, W. S. (2024) · Annual Review of Physiology · doi:10.1146/annurev-physiol-042022-025619 · Cited by 78
Metadata
- Authors
- Hajishengallis, G.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Hajishengallis, George
- Venue
- Nature Reviews Immunology
- Published
- 2014-12-23
- Volume
- 15
- Issue
- 1
- Pages
- 30-44
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC4276050
- OpenAlex
- W2021838232
- Cited by
- 3,046
- References
- 175
- Citations by year
- 2026: 400 · 2025: 359 · 2024: 348 · 2023: 394 · 2022: 291 · 2021: 318 · 2020: 262 · 2019: 215 · 2018: 135 · 2017: 144 · 2016: 131 · 2015: 46
- FWCI
- 18.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 068730, P01AI068730)
- National Institute of Dental and Craniofacial Research (DE-015254, DE017138, R01DE015254, R01DE024716, DE021685, R01DE021685, R01DE017138)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › General Dentistry › Dental Research and COVID-19
- Keywords
- periodontitis, systemic inflammation, rheumatoid arthritis, oral dysbiosis, oral microbiota, oral-systemic disease link, host-pathogen interaction
- MeSH terms
- Animals, Antibiosis, Arthritis, Rheumatoid, Cardiovascular Diseases, Female, Humans, Immunity, Periodontitis, Pregnancy, Pregnancy Outcome, Respiratory Tract Diseases, Symbiosis
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