Seminar: Pathogen Dynamics and Lasting Host Consequences of Early-Life Enteric Infection: Microbial Signals at the Crossroads of Gut and Brain

Abstract: Early life represents a critical window for the establishment of the intestinal ecosystem, when pathogenic insults exert lasting consequences within and beyond the gut. Notably, early-life enteric infections are established risk factors for neurodevelopmental disorders; however, the molecular mechanisms that mediate this gut-brain connection during formative developmental stages remain largely unresolved. Using the murine pathogen Citrobacter rodentium as a model of enteric infection, we demonstrate that transient postnatal infection disrupts hippocampal development through cell-type-specific alterations, resulting in persistent cognitive deficits. We further identified a key microbial metabolite that intensifies C. rodentium infection dynamics and aggravates gut–brain effects. Our work demonstrates how early-life enteric infection shapes neurodevelopment and reveals how enteric pathogens adapt to environmental cues to exacerbate disease outcomes.