Cargando…

Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial

There is a growing body of evidence which suggests that intestinal microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with intestinal immune disease such as ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal epithelial cell (IEC) death remaine...

Descripción completa

Detalles Bibliográficos
Autores principales: Su, Wenhao, Chen, Yongyu, Cao, Pan, Chen, Yan, Guo, Yuanmei, Wang, Siwei, Dong, Weiguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728699/
https://www.ncbi.nlm.nih.gov/pubmed/33330137
http://dx.doi.org/10.3389/fcimb.2020.594806
_version_ 1783621325359677440
author Su, Wenhao
Chen, Yongyu
Cao, Pan
Chen, Yan
Guo, Yuanmei
Wang, Siwei
Dong, Weiguo
author_facet Su, Wenhao
Chen, Yongyu
Cao, Pan
Chen, Yan
Guo, Yuanmei
Wang, Siwei
Dong, Weiguo
author_sort Su, Wenhao
collection PubMed
description There is a growing body of evidence which suggests that intestinal microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with intestinal immune disease such as ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal epithelial cell (IEC) death remained undefined. Here, we investigated the potential mechanisms about how F. nucleatum aggravates IEC death in UC. We first detected the abundance of F. nucleatum in UC tissues and analyzed its relationship with the clinical characteristics of UC. Next, we explored whether F. nucleatum promotes intestinal epithelial cell death in vitro and in vivo. Furthermore, we extracted lipopolysaccharide (LPS) of the F. nucleatum and examined whether F. nucleatum exacerbates UC via LPS. Our results indicated that F. nucleatum was abundant in UC tissues and was correlated with clinical characteristics. In addition, we demonstrated that F. nucleatum and its LPS aggravated IEC death by promoted IEC autophagy. Furthermore, autophagy inhibitors, chloroquine (CQ), 3-methyladenine (3-MA) or Atg5 silencing prevented IEC death mediated by F. nucleatum, which suggests F. nucleatum may contribute to UC by activating autophagic cell death. All our results uncover a vital role of F. nucleatum in autophagic cell death and UC, giving rise to a new sight for UC therapy by inhibiting excessive IEC autophagy and autophagic cell death.
format Online
Article
Text
id pubmed-7728699
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77286992020-12-15 Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial Su, Wenhao Chen, Yongyu Cao, Pan Chen, Yan Guo, Yuanmei Wang, Siwei Dong, Weiguo Front Cell Infect Microbiol Cellular and Infection Microbiology There is a growing body of evidence which suggests that intestinal microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with intestinal immune disease such as ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal epithelial cell (IEC) death remained undefined. Here, we investigated the potential mechanisms about how F. nucleatum aggravates IEC death in UC. We first detected the abundance of F. nucleatum in UC tissues and analyzed its relationship with the clinical characteristics of UC. Next, we explored whether F. nucleatum promotes intestinal epithelial cell death in vitro and in vivo. Furthermore, we extracted lipopolysaccharide (LPS) of the F. nucleatum and examined whether F. nucleatum exacerbates UC via LPS. Our results indicated that F. nucleatum was abundant in UC tissues and was correlated with clinical characteristics. In addition, we demonstrated that F. nucleatum and its LPS aggravated IEC death by promoted IEC autophagy. Furthermore, autophagy inhibitors, chloroquine (CQ), 3-methyladenine (3-MA) or Atg5 silencing prevented IEC death mediated by F. nucleatum, which suggests F. nucleatum may contribute to UC by activating autophagic cell death. All our results uncover a vital role of F. nucleatum in autophagic cell death and UC, giving rise to a new sight for UC therapy by inhibiting excessive IEC autophagy and autophagic cell death. Frontiers Media S.A. 2020-11-27 /pmc/articles/PMC7728699/ /pubmed/33330137 http://dx.doi.org/10.3389/fcimb.2020.594806 Text en Copyright © 2020 Su, Chen, Cao, Chen, Guo, Wang and Dong http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Su, Wenhao
Chen, Yongyu
Cao, Pan
Chen, Yan
Guo, Yuanmei
Wang, Siwei
Dong, Weiguo
Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial
title Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial
title_full Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial
title_fullStr Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial
title_full_unstemmed Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial
title_short Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial
title_sort fusobacterium nucleatum promotes the development of ulcerative colitis by inducing the autophagic cell death of intestinal epithelial
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728699/
https://www.ncbi.nlm.nih.gov/pubmed/33330137
http://dx.doi.org/10.3389/fcimb.2020.594806
work_keys_str_mv AT suwenhao fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial
AT chenyongyu fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial
AT caopan fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial
AT chenyan fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial
AT guoyuanmei fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial
AT wangsiwei fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial
AT dongweiguo fusobacteriumnucleatumpromotesthedevelopmentofulcerativecolitisbyinducingtheautophagiccelldeathofintestinalepithelial