Bifidobacterium breve UCC2003 Induces a Distinct Global Transcriptomic Program in Neonatal Murine Intestinal Epithelial Cells
Raymond Kiu,
Agatha Treveil,
Lukas C. Harnisch,
Shabhonam Caim,
Charlotte Leclaire,
Douwe van Sinderen,
Tamas Korcsmaros,
Lindsay J. Hall
Affiliations
Raymond Kiu
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
Agatha Treveil
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; Earlham Institute, Norwich Research Park, Norwich NR4 7UZ, UK
Lukas C. Harnisch
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
Shabhonam Caim
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
Charlotte Leclaire
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
Douwe van Sinderen
APC Microbiome Ireland & School of Microbiology, University College Cork, Cork T12YT20, Ireland
Tamas Korcsmaros
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; Earlham Institute, Norwich Research Park, Norwich NR4 7UZ, UK
Lindsay J. Hall
Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK; Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK; Chair of Intestinal Microbiome, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany; ZIEL – Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany; Corresponding author
Summary: The underlying health-driving mechanisms of Bifidobacterium during 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 of Bifidobacterium breve UCC2003 on the transcriptome of neonatal murine IECs. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 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. breve UCC2003 plays a central role in driving intestinal epithelium homeostatic development during early life and suggests future avenues for next-stage clinical studies.