摘要:SummaryThe underlying health-driving mechanisms ofBifidobacteriumduring early life are not well understood, particularly how this microbiota member may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). We investigated the impact ofBifidobacterium breveUCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administeredB.breveUCC2003 or PBS (control) were subjected to global RNA sequencing, and differentially expressed genes, pathways, and affected cell types were determined. We observed extensive regulation of the IEC transcriptome with ∼4,000 genes significantly up-regulated, including key genes linked with epithelial barrier function. Enrichment of cell differentiation pathways was observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. In conclusion,B.breveUCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.Graphical AbstractDisplay OmittedHighlights•B. breveadministration significantly alters the murine neonatal IEC transcriptome•Genes/pathways involved in epithelial barrier function are particularly impacted•Bifidobacteriummay target the IEC stem cell compartment to induce regenerationMicrobiology; Microbiome; Transcriptomics