The Keystone Pathogen Hypothesis

By G. Hajishengallis, R. Darveau, M. Curtis. Nature Reviews Microbiology, 2012

1,618 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cf6a1301dcd100dab4ff9d4604f0cf1b93cf3814

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In Epidemiology

Gideon M. Hirschfield

In Molecular Biology

Citations in the corpus

Mechanisms of Bone Resorption in Periodontitis (2015, background): “Recent developments in the area of biological processes and mediators of osteoclast differentiation and activity have expanded our knowledge of resorption processes and set the stage for new diagnostic and therapeutic modalities to treat situations of localized bone loss as seen in periodontal disea”
Microbial Hub Taxa Link Host and Abiotic Factors to Plant Microbiome Variation (2016, background): “The hub status of these pathogens (and the dysbiotic microbiota they cause) is suggested to benefit them by promoting disease in the host [73].”
Identifying Keystone Species in the Human Gut Microbiome from Metagenomic Timeseries Using Sparse Linear Regression (2014, background): “Abundance of both Bacteroides fragilis and Bacteroides stercosis are associated with an increased risk of colon cancer [5,6,10], and previous authors even suggest that Bacteroides fragilis acts as a critical ‘‘keystone pathogen’’ in the development of the disease [8].”
Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line (2016, neutral): “Among major periodontal pathogens, P. gingivalis appears to be one of the prime etiological agents in the pathogenesis and progression of the inﬂammatory events of periodontal disease (Hajishengallis et al., 2012).”
Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology (2012, neutral): “…identification of keystone and accessory pathogens from the catalog of organisms generated by microbiome projects will present the next major challenge in periodontal disease research and, perhaps, in other inflammatory diseases with a complex polymicrobial etiology (Hajishengallis et al., 2012).”
The gut microbiota and host health: a new clinical frontier (2015, background): “The keystone-pathogen hypothesis 88 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…”