Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression

The colorectal cancer (CRC)-associated microbiota creates a pro-tumorigenic intestinal milieu and shapes immune responses within the tumor microenvironment. However, how oncomicrobes – like Fusobacterium nucleatum, found in the oral cavity and associated with CRC tissues– affect these distinct aspec...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Caitlin A. Brennan, Slater L. Clay, Sydney L. Lavoie, Sena Bae, Jessica K. Lang, Diogo Fonseca-Pereira, Kathryn G. Rosinski, Nora Ou, Jonathan N. Glickman, Wendy S. Garrett
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	microbiome colorectal cancer th17 cells interleukin 17 gnotobiotics fusobacterium nucleatum altered schaedler’s flora Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/a842a012067c4a7a9eac1f861b7fde86
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a842a012067c4a7a9eac1f861b7fde86
record_format	dspace
spelling	oai:doaj.org-article:a842a012067c4a7a9eac1f861b7fde862021-11-17T14:21:57ZFusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression1949-09761949-098410.1080/19490976.2021.1987780https://doaj.org/article/a842a012067c4a7a9eac1f861b7fde862021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1987780https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984The colorectal cancer (CRC)-associated microbiota creates a pro-tumorigenic intestinal milieu and shapes immune responses within the tumor microenvironment. However, how oncomicrobes – like Fusobacterium nucleatum, found in the oral cavity and associated with CRC tissues– affect these distinct aspects of tumorigenesis is difficult to parse. Herein, we found that neonatal inoculation of ApcMin/+ mice with F. nucleatum strain Fn7-1 circumvents technical barriers preventing its intestinal colonization, drives colonic Il17a expression prior to tumor formation, and potentiates intestinal tumorigenesis. Using gnotobiotic mice colonized with a minimal complexity microbiota (the altered Schaedler’s flora), we observed that intestinal Fn7-1 colonization increases colonic Th17 cell frequency and their IL-17A and IL-17F expression, along with a concurrent increase in colonic lamina propria Il23p19 expression. As Fn7-1 stably colonizes the intestinal tract in our models, we posited that microbial metabolites, specifically short-chain fatty acids (SCFA) that F. nucleatum abundantly produces in culture and, as we demonstrate, in the intestinal tract, might mediate part of its immunomodulatory effects in vivo. Supporting this hypothesis, we found that Fn7-1 did not alter RORγt+ CD4+T cell frequency in the absence of the SCFA receptor FFAR2. Taken together, our work suggests that F. nucleatum influences intestinal immunity by shaping Th17 responses in an FFAR2-dependent manner, although further studies are necessary to clarify the precise and multifaceted roles of FFAR2. The potential to increase intestinal Th17 responses is shared by another oncomicrobe, enterotoxigenic Bacteroides fragilis, highlighting a conserved pathway that could potentially be targeted to slow oncomicrobe-mediated CRC.Caitlin A. BrennanSlater L. ClaySydney L. LavoieSena BaeJessica K. LangDiogo Fonseca-PereiraKathryn G. RosinskiNora OuJonathan N. GlickmanWendy S. GarrettTaylor & Francis Grouparticlemicrobiomecolorectal cancerth17 cellsinterleukin 17gnotobioticsfusobacterium nucleatumaltered schaedler’s floraDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microbiome colorectal cancer th17 cells interleukin 17 gnotobiotics fusobacterium nucleatum altered schaedler’s flora Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	microbiome colorectal cancer th17 cells interleukin 17 gnotobiotics fusobacterium nucleatum altered schaedler’s flora Diseases of the digestive system. Gastroenterology RC799-869 Caitlin A. Brennan Slater L. Clay Sydney L. Lavoie Sena Bae Jessica K. Lang Diogo Fonseca-Pereira Kathryn G. Rosinski Nora Ou Jonathan N. Glickman Wendy S. Garrett Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
description	The colorectal cancer (CRC)-associated microbiota creates a pro-tumorigenic intestinal milieu and shapes immune responses within the tumor microenvironment. However, how oncomicrobes – like Fusobacterium nucleatum, found in the oral cavity and associated with CRC tissues– affect these distinct aspects of tumorigenesis is difficult to parse. Herein, we found that neonatal inoculation of ApcMin/+ mice with F. nucleatum strain Fn7-1 circumvents technical barriers preventing its intestinal colonization, drives colonic Il17a expression prior to tumor formation, and potentiates intestinal tumorigenesis. Using gnotobiotic mice colonized with a minimal complexity microbiota (the altered Schaedler’s flora), we observed that intestinal Fn7-1 colonization increases colonic Th17 cell frequency and their IL-17A and IL-17F expression, along with a concurrent increase in colonic lamina propria Il23p19 expression. As Fn7-1 stably colonizes the intestinal tract in our models, we posited that microbial metabolites, specifically short-chain fatty acids (SCFA) that F. nucleatum abundantly produces in culture and, as we demonstrate, in the intestinal tract, might mediate part of its immunomodulatory effects in vivo. Supporting this hypothesis, we found that Fn7-1 did not alter RORγt+ CD4+T cell frequency in the absence of the SCFA receptor FFAR2. Taken together, our work suggests that F. nucleatum influences intestinal immunity by shaping Th17 responses in an FFAR2-dependent manner, although further studies are necessary to clarify the precise and multifaceted roles of FFAR2. The potential to increase intestinal Th17 responses is shared by another oncomicrobe, enterotoxigenic Bacteroides fragilis, highlighting a conserved pathway that could potentially be targeted to slow oncomicrobe-mediated CRC.
format	article
author	Caitlin A. Brennan Slater L. Clay Sydney L. Lavoie Sena Bae Jessica K. Lang Diogo Fonseca-Pereira Kathryn G. Rosinski Nora Ou Jonathan N. Glickman Wendy S. Garrett
author_facet	Caitlin A. Brennan Slater L. Clay Sydney L. Lavoie Sena Bae Jessica K. Lang Diogo Fonseca-Pereira Kathryn G. Rosinski Nora Ou Jonathan N. Glickman Wendy S. Garrett
author_sort	Caitlin A. Brennan
title	Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
title_short	Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
title_full	Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
title_fullStr	Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
title_full_unstemmed	Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
title_sort	fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of il-17 expression
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/a842a012067c4a7a9eac1f861b7fde86
work_keys_str_mv	AT caitlinabrennan fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT slaterlclay fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT sydneyllavoie fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT senabae fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT jessicaklang fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT diogofonsecapereira fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT kathryngrosinski fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT noraou fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT jonathannglickman fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression AT wendysgarrett fusobacteriumnucleatumdrivesaproinflammatoryintestinalmicroenvironmentthroughmetabolitereceptordependentmodulationofil17expression
_version_	1718425501878452224

Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression

Ejemplares similares