Supported by Crohn's in Childhood Research Appeal (CICRA) charity.
Aberrant response to commensal Bacteroides thetaiotaomicron in Crohn's disease: An ex vivo human organ culture study†
Article first published online: 25 OCT 2010
Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 5, pages 1201–1208, May 2011
How to Cite
Edwards, L.A., Lucas, M., Edwards, E.A., Torrente, F., Heuschkel, R.B., Klein, N.J., Murch, S.H., Bajaj-Elliott, M. and Phillips, A.D. (2011), Aberrant response to commensal Bacteroides thetaiotaomicron in Crohn's disease: An ex vivo human organ culture study. Inflamm Bowel Dis, 17: 1201–1208. doi: 10.1002/ibd.21501
- Issue published online: 11 APR 2011
- Article first published online: 25 OCT 2010
- Manuscript Accepted: 23 AUG 2010
- Manuscript Received: 16 AUG 2010
- microbial epithelial cell interactions;
- innate immune system in IBD;
- mucosal immunology;
- infectious agents in IBD;
Human ex vivo evidence indicating that an inappropriate immune response(s) to nonpathogenic bacteria contributes to disease pathogenesis in pediatric Crohn's disease (CD) is limited. The aim of the present study was to compare and contrast the early innate immune response of pediatric “healthy” versus CD mucosa to pathogenic, probiotic, and commensal bacteria.
“Healthy control” and CD pediatric mucosal biopsies (terminal ileum and transverse colon) were cocultured for 8 hours with E. coli O42, Lactobacillus GG (LGG), Bacteroidesthetaiotaomicron (B. theta), or stimulated with interleukin (IL)-1β (positive control). Matched nonstimulated biopsies served as experimental controls. IL-8 was the immune marker of choice. IL-8 mRNA and protein levels were quantified by quantitative polymerase chain reaction and sandwich enzyme-linked immunosorbent assay, respectively.
IL-8 secretion was observed when control, ileal biopsies were exposed to pathogenic O42 and probiotic LGG, with no response noted to commensal B. theta. In comparison, Crohn's ileal biopsies showed impaired ability to induce IL-8 in response to O42 and LGG. Control colonic tissue showed a limited response to O42 or B. theta and LGG significantly reduced IL-8 secretion. Unlike control tissue, however, Crohn's ileal and colonic tissue did respond to B. theta, with more enhanced expression in the colon.
We provide the first ex vivo data to support the notion that aberrant mucosal recognition of commensal bacteria may contribute to pediatric CD. While IL-8 responses to O42 and LGG varied with disease status and anatomical location, B. theta consistently induced significant IL-8 both in ileal and colonic CD tissue, which was not seen in control, healthy tissue. (Inflamm Bowel Dis 2010;)