Disruption of IgA-mediated aggregation at weaning favors mucus encroachment by commensal bacteria.

Disruption of the gut mucus barrier is critical in the development of infectious or chronic inflammatory diseases. The suckling-to-weaning transition is pivotal to the barrier maturation and is associated with a high incidence of gastrointestinal infections. Using a novel microfluidic device, we investigated the penetration and organizational properties of motile Escherichia coli bacteria at the interface of purified intestinal mucus from piglets before and after weaning. In weaned piglets, bacteria penetrated more than 100 μm into the mucus. Meanwhile, significant bacterial aggregation was observed in the mucus of suckling piglets, hindering penetration. Although we observed, on average, higher immunoglobulin A (IgA) concentrations in suckling piglet mucus, the high variability across samples suggested that concentration alone is insufficient to account for the aggregation behavior. Supernatant from purified suckling piglet mucus restored bacterial aggregation and limited penetration in weaned piglet mucus, similar to the effect observed with human breast milk IgA. Our results emphasize the importance of mucosal IgA specificity in relation to the mother's immunological history, primarily transmitted through breast milk and lost during weaning. This microfluidic ex-vivo approach provides an original platform to interrogate bacterial behavior in complex mucosal environments, opening new avenues for predictive and translational research.