The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer

ABSTRACT Many patients with chronic inflammation of the gut, such as that observed in inflammatory bowel disease (IBD), develop colorectal cancer (CRC). Recent studies have reported that the development of IBD and CRC partly results from an imbalanced composition of intestinal microbiota and that in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yun Kyung Lee, Parpi Mehrabian, Silva Boyajian, Wei-Li Wu, Jane Selicha, Steven Vonderfecht, Sarkis K. Mazmanian
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Bacteroides fragilis Toll-like receptor 2 colitis-associated colorectal cancer inflammation polysaccharide A Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a87822a7b9fd4c038c450ace343e5aa0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a87822a7b9fd4c038c450ace343e5aa0
record_format	dspace
spelling	oai:doaj.org-article:a87822a7b9fd4c038c450ace343e5aa02021-11-15T15:22:21ZThe Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer10.1128/mSphere.00587-182379-5042https://doaj.org/article/a87822a7b9fd4c038c450ace343e5aa02018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00587-18https://doaj.org/toc/2379-5042ABSTRACT Many patients with chronic inflammation of the gut, such as that observed in inflammatory bowel disease (IBD), develop colorectal cancer (CRC). Recent studies have reported that the development of IBD and CRC partly results from an imbalanced composition of intestinal microbiota and that intestinal inflammation in these diseases can be modulated by the microbiota. The human commensal Bacteroides fragilis is best exemplified playing a protective role against the development of experimental colitis in several animal disease models. In this study, we found that gut inflammation caused by dextran sulfate sodium (DSS) treatment was inhibited by B. fragilis colonization in mice. Further, we reveal a protective role of B. fragilis treatment against colon tumorigenesis using an azoxymethane (AOM)/DSS-induced model of colitis-associated colon cancer in mice and demonstrate that the decreased tumorigenesis by B. fragilis administration is accompanied by inhibited expression of C-C chemokine receptor 5 (CCR5) in the gut. We show direct evidence that the inhibition of tumor formation provided by B. fragilis in colitis-associated CRC animals was dependent on the production of polysaccharide A (PSA) from B. fragilis and that Toll-like receptor 2 (TLR2) signaling was responsible for the protective function of B. fragilis. IMPORTANCE The incidence of colorectal cancer (CRC) is rapidly growing worldwide, and there is therefore a greater emphasis on studies of the treatment or prevention of CRC pathogenesis. Recent studies suggested that consideration of the microbiota is unavoidable to understand inflammation and tumorigenesis in the gastrointestinal tract. We demonstrate, using a mouse model of colitis-associated CRC, that human commensal B. fragilis protects against colon tumorigenesis. The protective role against tumor formation provided by B. fragilis is associated with inhibition of expression of the chemokine receptor CCR5 in the colon. The molecular mechanism for protection against CRC provided by B. fragilis is dependent on polysaccharide A production and is mediated by TLR2 signaling. Our results suggest that the commensal microorganism B. fragilis can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC.Yun Kyung LeeParpi MehrabianSilva BoyajianWei-Li WuJane SelichaSteven VonderfechtSarkis K. MazmanianAmerican Society for MicrobiologyarticleBacteroides fragilisToll-like receptor 2colitis-associated colorectal cancerinflammationpolysaccharide AMicrobiologyQR1-502ENmSphere, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bacteroides fragilis Toll-like receptor 2 colitis-associated colorectal cancer inflammation polysaccharide A Microbiology QR1-502
spellingShingle	Bacteroides fragilis Toll-like receptor 2 colitis-associated colorectal cancer inflammation polysaccharide A Microbiology QR1-502 Yun Kyung Lee Parpi Mehrabian Silva Boyajian Wei-Li Wu Jane Selicha Steven Vonderfecht Sarkis K. Mazmanian The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer
description	ABSTRACT Many patients with chronic inflammation of the gut, such as that observed in inflammatory bowel disease (IBD), develop colorectal cancer (CRC). Recent studies have reported that the development of IBD and CRC partly results from an imbalanced composition of intestinal microbiota and that intestinal inflammation in these diseases can be modulated by the microbiota. The human commensal Bacteroides fragilis is best exemplified playing a protective role against the development of experimental colitis in several animal disease models. In this study, we found that gut inflammation caused by dextran sulfate sodium (DSS) treatment was inhibited by B. fragilis colonization in mice. Further, we reveal a protective role of B. fragilis treatment against colon tumorigenesis using an azoxymethane (AOM)/DSS-induced model of colitis-associated colon cancer in mice and demonstrate that the decreased tumorigenesis by B. fragilis administration is accompanied by inhibited expression of C-C chemokine receptor 5 (CCR5) in the gut. We show direct evidence that the inhibition of tumor formation provided by B. fragilis in colitis-associated CRC animals was dependent on the production of polysaccharide A (PSA) from B. fragilis and that Toll-like receptor 2 (TLR2) signaling was responsible for the protective function of B. fragilis. IMPORTANCE The incidence of colorectal cancer (CRC) is rapidly growing worldwide, and there is therefore a greater emphasis on studies of the treatment or prevention of CRC pathogenesis. Recent studies suggested that consideration of the microbiota is unavoidable to understand inflammation and tumorigenesis in the gastrointestinal tract. We demonstrate, using a mouse model of colitis-associated CRC, that human commensal B. fragilis protects against colon tumorigenesis. The protective role against tumor formation provided by B. fragilis is associated with inhibition of expression of the chemokine receptor CCR5 in the colon. The molecular mechanism for protection against CRC provided by B. fragilis is dependent on polysaccharide A production and is mediated by TLR2 signaling. Our results suggest that the commensal microorganism B. fragilis can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC.
format	article
author	Yun Kyung Lee Parpi Mehrabian Silva Boyajian Wei-Li Wu Jane Selicha Steven Vonderfecht Sarkis K. Mazmanian
author_facet	Yun Kyung Lee Parpi Mehrabian Silva Boyajian Wei-Li Wu Jane Selicha Steven Vonderfecht Sarkis K. Mazmanian
author_sort	Yun Kyung Lee
title	The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer
title_short	The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer
title_full	The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer
title_fullStr	The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer
title_full_unstemmed	The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer
title_sort	protective role of <italic toggle="yes">bacteroides fragilis</italic> in a murine model of colitis-associated colorectal cancer
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/a87822a7b9fd4c038c450ace343e5aa0
work_keys_str_mv	AT yunkyunglee theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT parpimehrabian theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT silvaboyajian theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT weiliwu theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT janeselicha theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT stevenvonderfecht theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT sarkiskmazmanian theprotectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT yunkyunglee protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT parpimehrabian protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT silvaboyajian protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT weiliwu protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT janeselicha protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT stevenvonderfecht protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer AT sarkiskmazmanian protectiveroleofitalictoggleyesbacteroidesfragilisitalicinamurinemodelofcolitisassociatedcolorectalcancer
_version_	1718428023827464192

The Protective Role of <italic toggle="yes">Bacteroides fragilis</italic> in a Murine Model of Colitis-Associated Colorectal Cancer

Ejemplares similares