AUTHOR=Cao Pan , Chen Yongyu , Guo Xufeng , Chen Yan , Su Wenhao , Zhan Na , Dong Weiguo 

TITLE=Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00106

DOI=10.3389/fphar.2020.00106

ISSN=1663-9812

ABSTRACT=<p>There is increasing evidence that members of the gut microbiota, especially <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>), are associated with Crohn’s disease (CD), but the specific mechanism by which <italic>F. nucleatum</italic> promotes CD development is unclear. Here, we first examined the abundance of <italic>F. nucleatum</italic> and its effects on CD disease activity and explored whether <italic>F. nucleatum</italic> aggravated intestinal inflammation and promoted intestinal mucosal barrier damage <italic>in vitro</italic> and <italic>in vivo</italic>. Our data showed that <italic>F. nucleatum</italic> was enriched in 41.21% of CD tissues from patients and was correlated with the clinical course, clinical activity, and refractory behavior of CD <italic>(P</italic> &lt; 0.05). In addition, we found that <italic>F. nucleatum</italic> infection is involved in activating the endoplasmic reticulum stress (ERS) pathway during CD development to promote intestinal mucosal barrier destruction. Mechanistically, <italic>F. nucleatum</italic> targeted caspase activation and recruitment domain 3 (CARD3) to activate the ERS pathway and promote <italic>F. nucleatum</italic>-mediated mucosal barrier damage <italic>in vivo</italic> and <italic>in vitro</italic>. Thus, <italic>F. nucleatum</italic> coordinates a molecular network involving CARD3 and ERS to control the CD process. Measuring and targeting <italic>F. nucleatum</italic> and its associated pathways will provide valuable insight into the prevention and treatment of CD.</p>