Pathobionts of the gastrointestinal microbiota and inflammatory disease

Abstract

Our immune system is charged with the vital mission of identifying invading pathogens and mounting proper inflammatory responses. During the process of clearing infections, the immune system often causes considerable tissue damage. Conversely, if the target of immunity is a member of the resident microbiota, uncontrolled inflammation may lead to host pathology in the absence of infectious agents. Recent evidence suggests that several inflammatory disorders may be caused by specific bacterial species found in most healthy hosts. Although the mechanisms that mediate pathology remain largely unclear, it appears that genetic defects and/or environmental factors may predispose mammals to immune-mediated diseases triggered by potentially pathogenic symbionts of the microbiota. We have termed this class of microbes 'pathobionts', to distinguish them from acquired infectious agents. Herein, we explore burgeoning hypotheses that the combination of an immunocompromised state with colonization by pathobionts together comprise a risk factor for certain inflammatory disorders and gastrointestinal (GI) cancer.

Figure 1. Genetic and environmental alterations may synergize with pathobionts to cause intestinal inflammation and disease

In addition to acquired pathogens which can cause gastroenteritis, resident gut bacteria trigger intestinal inflammation. However, unlike acute pathogens, pathobionts appear to require additional factors to cause disease. Based predominantly on animal models, certain symbionts of the microbiota can initiation gut inflammation and pathology when colonizing a genetically susceptible host (e.g., H. hepaticus, SFB, P. mirabilis & K. pneumonia, Prevotellaceae and TM7). In other cases, specific resident gut bacteria can expand following antibiotic use which clears competing symbionts to promote gastrointestinal disease (VRE, C. difficile). The associated genetic defects or antibiotics are denoted in parenthesis.