Bifidobacterium breve UCC2003 Induces a Distinct Global Transcriptomic Program in Neonatal Murine Intestinal Epithelial Cells.

Raymond Kiu,Douwe Van Sinderen,Charlotte Leclaire,Lindsay J Hall,Shabhonam Caim,Lukas C Harnisch,Agatha Treveil,Tamas Korcsmaros

doi:10.1016/j.isci.2020.101336

Abstract

SummaryThe 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.

Highlights

Bifidobacterium represents a keystone member of the early life gut microbiota (Arrieta et al, 2014; O’Neill et al, 2017; Derrien et al, 2019)
SUMMARY The underlying health-driving mechanisms of Bifidobacterium during early life are not well understood, 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

Summary

Introduction

Bifidobacterium represents a keystone member of the early life gut microbiota (Arrieta et al, 2014; O’Neill et al, 2017; Derrien et al, 2019). Previous work by our group has shown that infant-associated B. breve UCC2003 modulates cell death-related signaling molecules, which in turn reduces the number of apoptotic IECs (Hughes et al, 2017). This protection from pathological IEC shedding appeared to be via the B. breve exopolysaccharide (EPS) capsule and the host-immune adaptor protein MyD88. Another strain of B. breve, NumRes 204 (commercial strain) has been shown to up-regulate the tight junction (TJ) proteins Claudin 4 and Occludin in a mouse colitis model (Zheng et al, 2014; Plantinga et al, 2011)

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