Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (
EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal
immune disorders. This study was performed using the
dextran sodium sulphate (DSS)-induced
colitis mouse model, which is routinely used to evaluate potential
therapeutics for the treatment of
Inflammatory Bowel Diseases (IBDs). We focused on the analysis of
flagellin structures of different E. coli strains.
EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of
Toll-like receptor (TLR)5, thereby resulting in
interleukin (IL)-22-mediated protection of mice against DSS-induced
colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these
flagellin-induced symbiotic effects. We propose
flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.