Immune control of the gut microbiota via avoidance and tolerance

The mammalian gut microbiome is a complex ecosystem that provides metabolic and immunological benefits to its host. However, some gut microbes can cross the gut epithelium barrier, thereby harming the host. Furthermore, the microbe composition of the gut fluctuates in response to variations in the environment and nutrient availability. This ecology interacts with the host immune system, which can act as a controller, toggling between avoidance or tolerance of microbes, and their associated harms and benefits. How should the immune system monitor the gut ecology to optimize beneficial function while maintaining immunity? Using a generalized consumer-resource model coupled with a model for the tolerogenic and humoral immune responses, we investigate how host-supplied nutrients impact the composition of commensal microbes in the gut, and how in turn the microbial ecology can confer a metabolic benefit to the host. Our model sheds light on the constraints that the microbiome ecology imposes on immune control and vice versa. We also explore the hypothesis that the immune repertoire contains information about the composition-to-function mapping of the gut; for instance, identifying which compositional patterns are beneficial/harmful. We argue that since the gut microbiota is personalized amongst individuals, its specific composition is likely less important than its collective function.