Bifidobacterium breveUCC2003 induces a distinct global transcriptomic programme in neonatal murine intestinal epithelial cells

Abstract

SummaryBifidobacterium is an important gut microbiota member during early life that is associated with improved gut health. However, the underlying health-driving mechanisms are not well understood, particularly how Bifidobacterium may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). In this study, we sought to investigate the global impact of model strain Bifidobacterium breve UCC2003 on the neonatal IEC transcriptome, including gene regulation and pathway modulation. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 for three consecutive days or PBS (control group) were subjected to global RNASeq, with various bioinformatic approaches used to determine differentially expressed genes, pathways and affected cell types between control and experimental groups. Whilst colonisation with B. breve had minimal impacts on the neonatal microbiota, we observed extensive regulation of the IEC transcriptome; ~4,000 genes significantly up-regulated, including key genes associated with epithelial barrier function. Enrichment of cell differentiation and cell proliferation pathways were observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. Expression of distinct immune-associated pathway members (e.g. Toll-like Receptors) were also affected after neonatal B. breve colonisation. In conclusion, B. breve UCC2003 plays a central role in driving universal transcriptomic changes in neonatal IECs that enhances cell replication, differentiation and growth, predominantly in the stem cell compartment. This study enhances our overall understanding of the benefits of B. breve in driving intestinal epithelium homeostatic development during early life, with potential avenues to develop novel live biotherapeutic products.

Serpin-positive Bifidobacterium breve CNCM I-5644 improves intestinal permeability in two models of irritable bowel syndrome

“…Tight junctions upregulation by B. longum is associated with signaling through TLR2, the major pattern recognition receptor for Gram-positive bacteria 42 . Taken together, our results are consistent with other studies on Bifidobacterium species 39,43,44 . Proinflammatory cytokines also contribute to alterations in gut permeability: IL-4 induces epithelial hypertrophy, IL-5 promotes eosinophil cellular infiltration and IL-6 modulates the excitability of submucosal neurons and increases colonic secretory function 45 .…”