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

K R Hughes,J Ketskemety,D Van Sinderen,L J Hall,A J M Watson,L C Harnisch,C Alcon-Giner,C J Wright,S Mitra

doi:10.1098/rsob.160155

K R Hughes, J Ketskemety + Show 7 more

Open Access

https://doi.org/10.1098/rsob.160155

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Abstract

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 (IECs) from villi—a process termed ‘cell shedding’. Using a mouse model of pathological cell shedding, we show that mice receiving Bifidobacterium breve UCC2003 exhibit significantly reduced rates of small IEC 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 inflammatory 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.

Highlights

Bifidobacteria represent one of the first colonizers of the infant gut and are prominent members of the adult gut microbiota [1,2]
We found that control C57 BL/6 mice receiving IP PBS injection showed low levels of cell shedding as evidenced by low level expression of cleaved caspase-3 (CC3) in the epithelial cell layer
Recent studies have demonstrated that following IP injection of mice with LPS isolated from Escherichia coli 0111:B4, a potent cell shedding response is induced, similar to that observed in relapsing inflammatory bowel disease (IBD) patients [22]

Summary

Introduction

Bifidobacteria represent one of the first colonizers of the infant gut and are prominent members of the adult gut microbiota [1,2] They have been linked to a number of health-promoting activities, including the promotion of anti-tumour immunity [3], modulation of antimicrobial activities against pathogenic bacteria [4] and protection against relapse of ulcerative colitis [5,6]. There is a growing body of evidence suggesting that the microbiota influences intestinal epithelial cell (IEC) function, including gene expression, cell division and energy balance [8 –11]. These symbiotic bacterial/host relationships have co-evolved to the extent that the microbiota is indispensable for the maintenance of gut homeostasis [12]. Microbial dysbiosis, as indicated by a reduction in overall diversity, including specific reductions in Bifidobacterium, has been linked to inflammatory bowel disease (IBD) [13,14,15], underlining the critical importance of host/microbe interactions in maintaining a steady state within the intestine

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