AUTHOR=Su Wenhao , Chen Yongyu , Cao Pan , Chen Yan , Guo Yuanmei , Wang Siwei , Dong Weiguo 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.594806

DOI=10.3389/fcimb.2020.594806

ISSN=2235-2988

ABSTRACT=<p>There is a growing body of evidence which suggests that intestinal microbiota, especially <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>), are associated with intestinal immune disease such as ulcerative colitis (UC). The mechanism by which <italic>F. nucleatum</italic> promotes intestinal epithelial cell (IEC) death remained undefined. Here, we investigated the potential mechanisms about how <italic>F. nucleatum</italic> aggravates IEC death in UC. We first detected the abundance of <italic>F. nucleatum</italic> in UC tissues and analyzed its relationship with the clinical characteristics of UC. Next, we explored whether <italic>F. nucleatum</italic> promotes intestinal epithelial cell death <italic>in vitro</italic> and <italic>in vivo</italic>. Furthermore, we extracted lipopolysaccharide (LPS) of the <italic>F. nucleatum</italic> and examined whether <italic>F. nucleatum</italic> exacerbates UC <italic>via</italic> LPS. Our results indicated that <italic>F. nucleatum</italic> was abundant in UC tissues and was correlated with clinical characteristics. In addition, we demonstrated that <italic>F. nucleatum</italic> 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 <italic>F. nucleatum</italic>, which suggests <italic>F. nucleatum</italic> may contribute to UC by activating autophagic cell death. All our results uncover a vital role of <italic>F. nucleatum</italic> in autophagic cell death and UC, giving rise to a new sight for UC therapy by inhibiting excessive IEC autophagy and autophagic cell death.</p>