title: Bifidobacterium breve reduces apoptotic epithelial cell shedding in an exopolysaccharide and MyD88-dependent manner.
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.
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK kevinhughes79@gmail.com.|Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.
authors.forename: K R
authors.initials: KR
authors.lastname: Hughes
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.|Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Harnisch
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: C
authors.initials: C
authors.lastname: Alcon-Giner
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mitra
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.|Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Wright
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ketskemety
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: D
authors.identifier: 0000-0003-1823-7957
authors.initials: D
authors.lastname: van Sinderen
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK alastair.watson@uea.ac.uk.|Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.
authors.forename: A J M
authors.identifier: 0000-0003-3326-0426
authors.initials: AJ
authors.lastname: Watson
authors.affiliation: The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK lindsay.hall@ifr.ac.uk.
authors.forename: L J
authors.identifier: 0000-0001-8938-5709
authors.initials: LJ
authors.lastname: Hall
mesh_terms: D000818:Animals; D017209:Apoptosis; D000069984:Bifidobacterium breve / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007421:Intestine, Small / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011135:Polysaccharides, Bacterial
keywords: Bifidobacterium; epithelial cell shedding; exopolysaccharide; inflammatory bowel disease