Protective microbiomes can limit the evolution of host pathogen defense.

The evolution of host immunity occurs in the context of the microbiome, but little theory exists to predict how resistance against pathogens might be influenced by the need to tolerate and regulate commensal microbiota. We present a general model to explore the optimal investment in host immunity under conditions in which the host can, versus cannot easily distinguish among commensal versus pathogenic bacteria, and when commensal microbiota can, versus cannot protect the host against the impacts of pathogen infection. We find that a loss of immune vigilance associated with innate immunity over evolutionary time can occur due to the challenge of discriminating between pathogenic and other microbe species.