The Influence of Host Stress on the Mechanism of Infection: Lost Microbiomes, Emergent Pathobiomes, and the Role of Interkingdom Signaling

Mammals constantly face stressful situations, be it extended periods of starvation, sleep deprivation from fear of predation, changing environmental conditions, or loss of habitat. Today, mammals are increasingly exposed to xenobiotics such as pesticides, pollutants, and antibiotics. Crowding conditions such as those created for the purposes of meat production from animals or those imposed upon humans living in urban environments or during world travel create new levels of physiologic stress. As such, human progress has led to an unprecedented exposure of both animals and humans to accidental pathogens (i.e., those that have not co-evolved with their hosts). Strikingly missing in models of infection pathogenesis are the various elements of these conditions, in particular host physiologic stress. The compensatory factors released in the gut during host stress have profound and direct effects on the metabolism and virulence of the colonizing microbiota and the emerging pathobiota. Here, we address unanswered questions to highlight the relevance and importance of incorporating host stress to the field of microbial pathogenesis.