Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner

Certain members of the microbiota genus Bifidobacterium, are known to positively influence host well-being. Importantly, reduced bifidobacterial levels are associated with Inflammatory Bowel Disease (IBD) patients, who also have impaired epithelial barrier function, including elevated rates of apoptotic extrusion of small intestinal epithelial cells from villi; a process, termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving B. breve UCC2003 exhibit significantly reduced rates of small intestinal epithelial cell shedding. Bifidobacterial-induced protection appears to be mediated by a specific bifidobacterial surface exopolysaccharide and interactions with host MyD88 resulting in downregulation of intrinsic and extrinsic apoptotic responses to protect epithelial cells under highly apoptotic conditions. Our results reveal an important and previously undescribed role for B. breve, in positively modulating epithelial cell shedding outcomes via bacterial- and host-dependent factors, supporting the notion that manipulation of the microbiota affects intestinal disease outcomes.