Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
Authors: Xufeng Guo
Yan Chen
Pan Cao
Wenhao Su
Yongyu Chen
Weiguo Dong
Na Zhan
Journal: Frontiers in Pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Crohn’s disease; Fusobacterium nucleatum; endoplasmic reticulum stress; gene regulation; intestinal mucosal barrier.
Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China., Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China., Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

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

Retracted: No

PubPeer comments:
 Figure 2 appears to have a repeated image. *** ![file] , 
 #1 Thanku00a0youu00a0foru00a0the commentu00a0concerningu00a0ouru00a0manuscript entitledu00a0u201cFusobacterium nucleatum activates endoplasmic reticulum stress to promote Crohn s disease development via the upregulation of CARD3 expressionu201d. The carelessness in combining the images caused the repetition of the images. We are very sorry that our negligence caused the problem. We have replaced it with the correct image and will contact with the  Frontiers in Pharmacology to correct it. We feel fortunate that the comment will help improve our manuscript and we are once again deeply sorry for the problem caused by our negligence. , 
 #2 I thank the author for replying. Given the propensity of what appears to be the same research group to carelessly commingle images (see thread below), I would think it is difficult to trust the research results from this lab. https: pubpeer.com publications A22019AA1BEF68FCD1657F33C54116 , 
 Thank you for the comment. It is indeed because there are more research data, and these problems have been caused by negligence. We are actively checking and correcting the problems. Thank you again for your valuable comments. ,