Status: Funded - Open
Early environmental determinants predictive of autoimmunity in infants at risk of Celiac Disease
Maureen Leonard, MD, MMSc
BACKGROUND: The intestinal microbiome is extremely important to the development of the immune system and perturbations during its development have been suggested to increase the risk of future disease, including autoimmune disease. The prevalence of celiac disease is increasing and environmental factors, such as birthing delivery mode and antibiotic administration, have been implicated retrospectively as risk factors that may contribute to the development of celiac disease.
GAP: The proposed research will examine whether birthing delivery mode and antibiotic exposure influence the development of the microbiota during the first year of life in infants genetically at risk for celiac disease, providing a rationale to investigate alterations in the developing microbiota as future biomarkers predictive of disease.
HYPOTHESIS: Infants, genetically at risk for celiac disease, will have a particular intestinal microbiota composition that, in combination with other influential environmental factors, can contribute to the loss of gluten tolerance and to the onset of autoimmunity.
METHODS: This is a prospective, observational, pilot study that will utilize a nested case control analysis. The development of the intestinal microbiome during the first year of life in infants with a first degree family member with celiac disease, and thus at a high risk for celiac disease, will be evaluated.
IMPACT: This study will provide a foundation to establish biomarkers, identified as alterations in the microbiome that may signal the onset of disease and help to define novel diagnostic tools and therapeutic interventions. These findings may impact not only the 3 million patients with celiac disease in the U.S. but also patients with other pediatric autoimmune disease, such as type 1 diabetes.