The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.
The keystone-pathogen hypothesis
Open accessAbstract
Recent studies have highlighted the importance of the human microbiome in health and disease. However, for the most part the mechanisms by which the microbiome mediates disease, or protection from it, remain poorly understood. The keystone-pathogen hypothesis holds that certain low-abundance microbial pathogens can orchestrate inflammatory disease by remodelling a normally benign microbiota into a dysbiotic one. In this Opinion article, we critically assess the available literature that supports this hypothesis, which may provide a novel conceptual basis for the development of targeted diagnostics and treatments for complex dysbiotic diseases.
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“The genus Prevotella, including P. denticola, acts on the early and middle steps of oral biofilm formation with cellular adhesion for later colonizers and, in particular, supports the biofilm formation of Aggregatibacter actinomycetemcomitans [22,23].”
From Analysis of Chemical Structure and Antibiofilm Properties of Exopolysaccharides from Lactiplantibacillus plantarum EIR/IF-1 Postbiotics (2022) · cites this paper as [22]
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“The keystone-pathogen hypothesis88 and the α-bug hypothesis both state that certain, low abundance microbiota members (such as enterotoxigenic B. fragilis) possess unique virulence traits, which are pro-oncogenic and remodel the microbiome and in turn promote mucosal immune responses and colonic epithelial cell changes.89”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [88]
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A human gut microbial gene catalogue established by metagenomic sequencing
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Enterotypes of the human gut microbiome
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Food Web Complexity and Species Diversity
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Host-Bacterial Mutualism in the Human Intestine
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Microbial complexes in subgingival plaque
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A microbial symbiosis factor prevents intestinal inflammatory disease
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Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
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Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma
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NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
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Dumitru, C. N., Dumitru, A. O., Popa, G. V., Marcu, T., Ursu, M., Nechita, A., & Matei, N. M. (2026) · Dentistry Journal · doi:10.3390/dj14050289 · Cited by 6
“According to this model, P. gingivalis , although present in relatively low abundance, subverts host immune defenses through specific virulence mechanisms, thereby remodeling the commensal community into a dysbiotic one with enhanced inflammatory capacity [1,7,42].”
Metadata
- Authors
- Hajishengallis, G., Darveau, R. P., & Curtis, M. A.
- Affiliations
- University of Pennsylvania (US)
- University of Washington (US)
- Queen Mary University of London (GB)
- Corresponding author
- Hajishengallis, George
- Venue
- Nature Reviews Microbiology
- Published
- 2012-09-03
- Volume
- 10
- Issue
- 10
- Pages
- 717-725
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- PMC
- PMC3498498
- OpenAlex
- W2043248182
- Cited by
- 1,790
- References
- 86
- Citations by year
- 2026: 163 · 2025: 149 · 2024: 146 · 2023: 172 · 2022: 146 · 2021: 199 · 2020: 167 · 2019: 125 · 2018: 116 · 2017: 101 · 2016: 100 · 2015: 77 · 2014: 63 · 2013: 58 · 2012: 4
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Medical Research Council (MR/J011118/1)
- National Institute of Dental and Craniofacial Research (R01DE018292, DE-015254, R01DE015254, DE012768, DE021580, DE18274, DE021685, R01DE018274, DE018292, RC4DE021580, R01DE021685, R01DE012768)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- human microbiome, dysbiosis, commensal microbiota, inflammatory diseases, targeted therapeutics
- MeSH terms
- Bacteria, Colonic Neoplasms, Humans, Inflammation, Models, Biological, Periodontitis, Inflammatory Bowel Diseases, Host-Pathogen Interactions, Metagenome, Microbial Interactions
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