Host response to microbiota and novel pathogen co-colonization

The frequency of emerging disease is growing with ongoing human activity facilitating new host-pathogen interactions. Host microbiota has been shown to play a role in novel infection outcomes, either reducing or enhancing virulence; the latter is the most concerning for animal health in a changing world. Understanding the underlying host responses to microbiota-pathogen ecological interactions is key to pinpointing the mechanism underlying severe outcomes. We conducted transcriptomic analyses of Caenorhabditis elegans nematodes colonized by a wild microbiota community and infected by the widespread animal pathogen, Staphylococcus aureus. These co-colonized hosts have been shown to suffer higher mortality than those infected by the pathogen alone. Correlations between altered collagen gene expression and increased mortality in co-colonized hosts suggest the microbiota modifies host resistance to infection. Furthermore, microbiota colonized hosts showed increased expression of immunity genes and variable stress response gene expression during infection. Changes in host immunity and stress response could encompass both causes and effects of severe infection outcomes. By "re-wilding" this model nematode host with its natural microbiota, we obtained results indicating that host molecular changes mediated by typically commensal microbiota may incur significant costs when challenged by a novel emerging pathogen.