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

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

doi:10.1098/rsob.160155

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

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

^*Corresponding author for this work

Microbes, Infections and Microbiomes

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

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.

Original language	English
Article number	160155
Journal	Open Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1098/rsob.160155
Publication status	Published - 2017

Bibliographical note

Funding Information:
This work was supported via a Wellcome Trust New Investigator award to L.J.H. (100974/Z/13/Z), a Wellcome Trust grant awarded to A.J.M.W. (WT0087768MA), support of the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme grant for Gut Health and Food Safety BB/J004529/1 (L.J.H. and A.J.M.W.), and Science Foundation Ireland through the Irish Government's National Development Plan (grant number SFI/12/RC/2273, D.v.S.).

Publisher Copyright:
© 2017 The Authors.

Keywords

Bifidobacterium
Epithelial cell shedding
Exopolysaccharide
Inflammatory bowel disease

ASJC Scopus subject areas

General Neuroscience
Immunology
General Biochemistry,Genetics and Molecular Biology

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10.1098/rsob.160155

Cite this

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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.",

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author = "Hughes, {K. R.} and Harnisch, {L. C.} and C. Alcon-Giner and S. Mitra and Wright, {C. J.} and J. Ketskemety and {Van Sinderen}, D. and Watson, {A. J.M.} and Hall, {L. J.}",

note = "Funding Information: This work was supported via a Wellcome Trust New Investigator award to L.J.H. (100974/Z/13/Z), a Wellcome Trust grant awarded to A.J.M.W. (WT0087768MA), support of the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme grant for Gut Health and Food Safety BB/J004529/1 (L.J.H. and A.J.M.W.), and Science Foundation Ireland through the Irish Government's National Development Plan (grant number SFI/12/RC/2273, D.v.S.). Publisher Copyright: {\textcopyright} 2017 The Authors.",

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AU - Mitra, S.

AU - Wright, C. J.

AU - Ketskemety, J.

AU - Van Sinderen, D.

AU - Watson, A. J.M.

AU - Hall, L. J.

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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