A model of early-life interactions between the gut microbiome and adaptive immunity provides insights into the ontogeny of immune tolerance

To achieve immune and microbial homeostasis during adulthood, the developing immune system must learn to identify which microbes to tolerate and which to defend against. How such ‘immune education’ unfolds remains a major knowledge gap. We address this gap by synthesizing existing literature to develop a mechanistic mathematical model representing the interplay between gut ecology and adaptive immunity in humans during early life. Our results indicate that the inflammatory tone of the microenvironment is the mediator of information flow from pre- to post-weaning periods. We evaluate the power of postnatal fecal samples for predicting immunological trajectories and explore breastfeeding scenarios when maternal immunological conditions affect breastmilk composition. Our work establishes a quantitative basis for ‘immune education’, yielding insights into questions of applied relevance.