Interpreting infective microbiota: the importance of an ecological perspective

Abstract

Complex microbiota are being reported increasingly across a range of chronic infections, including those of the cystic fibrosis airways. Such diversity fits poorly into classical models of sterile tissue infections, which generally involve one species, and where microbe-outcome associations usually imply causality. It has been suggested that microbiota at sites of infection could represent pathogenic entities, analogous to individual species. We argue that our ability to identify causality in microbiota-disease associations is, however, inherently confounded. Although particular microbiota may be associated with clinical outcomes, niche characteristics at sites of infection will shape microbiota composition through exerting selective pressures. Here, we suggest that ecological theory can inform clinical understanding.

Figure 1

A proposed model of the relationship between the selective properties of the airway environment on microbiota membership and the ability of airway infection to promote damage. In early disease, the lower airway environment contains mild selective pressures and is colonised by a diverse array of bacterial species. Disease progression is contributed to by two separate processes: (A) members of the airway microbiota contribute to disease, either directly through exhibiting pathogenic traits, or indirectly, by augmenting the pathogenic behaviour of other species. (B) Increasing disease severity results in changes in the selective pressures on the infective microbiota, including levels of immune response and antibiotic exposure. These two scenarios are inherently linked, with changes in the airway environment, and the characteristics of the microbiota that infect it, proceeding together. We suggest that such a process could result in both the succession of bacterial species associated with different disease stages and the severely limited microbiota diversity associated with end-stage cystic fibrosis lung disease.