The keystone-pathogen hypothesis

Abstract

In this Opinion article, Hajishengallis and colleagues propose that certain low-abundance microorganisms, termed 'keystone pathogens', can disrupt a normally benign commensal microbiota, leading to a microbial community structure that is associated with the development of disease. 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.