Scientific Abstract

Proposal No. IBD-0204R2
Principal Investigator:  Scott M. Montgomery, Ph.D.
Applicant Organization:  Karolinska Institutet (Stockholm, Sweden)
Project Title:  Markers of perinatal bowel colonization and pediatric Crohn's disease risk
Period of Award:  September 1, 2007 – February 28, 2009

An inflammatory reaction to normal bowel flora is implicated in Crohn’s disease etiology.  Early microbial colonization may be important in stimulating appropriate immune development facilitating a stable homeostasis between host and gut flora.  Animal studies have indicated that perinatal microbial exposures may be important in stimulating innate immune recognition in intestinal epithelial cells: appropriate stimulation is more pronounced in vaginally delivered neonates, compared with those delivered by caesarean section.  This suggests that microbial colonization in the birth canal could be of particular importance in influencing future intestinal inflammatory responses to bowel flora and therefore, potentially, the risk of Crohn’s disease.

This epidemiological study will use the prospectively collected register data that is available for the general population in Sweden and can be linked for individuals and across generations using the unique personal identity number issued to all residents. Patients with a diagnosis of pediatric Crohn’s disease will be individually matched with controls of the same sex who were born in the same delivery unit during the same week. The controls will have been alive and resident in Sweden when their matched case received a diagnosis of Crohn’s disease. The analysis will use conditional logistic regression to prevent confounding by temporal variation and differences between delivery units.  Markers of the pattern of bowel colonization will include: maternal infections during pregnancy associated with antibiotic use (which will influence her bowel flora) and chronic maternal conditions associated with bowel motility and bacterial overgrowth; delivery mode (particularly by caesarian section) and other characteristics of delivery and perinatal handling of the infant; infections in the infant from birth to age five years that indicate antibiotic treatment as this disrupts the pattern of bowel colonization.  The role of younger siblings, associated with a reduced risk of Crohn’s disease, will be investigated.

This study may identify specific risks for Crohn’s disease that constitute useful targets for disease prevention, particularly among families with a history of the disease.  This will also provide well-defined objectives for further basic research.