Background & Purpose

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PURPOSE

JDRF is soliciting applications to investigate the role of the microbiome in type 1 diabetes (T1D).
JDRF is committed to and most interested in proposals that focus on research that provide insights into developing safe approaches to augment, accelerate, or induce robust microbiome-induced immunoregulation in childhood.

BACKGROUND

Recent evidence has demonstrated that the intestinal microbiota of young infants at risk for developing childhood-onset autoimmune and allergic disease is altered with differences in expression of LPS, a TLR- ligand, and degree of colonization with bifidobacteria. In addition, children who develop T1D have an altered intestinal microbiota with decreased diversity and greater instability to perturbations. The triggers or etiologies of these associations are incompletely understood and the mechanism(s) of their potential contribution to disease have not been elucidated. A greater understanding of the complex interactions between the intestinal microbiota and several interacting systems in the body (immune, intestinal integrity and function, metabolism, beta cell function, etc.) may provide both scientifically rational approaches to prevent development of childhood immune and allergic diseases and biomarkers to evaluate the efficacy of interventions.

The dynamic cross-talk between the microbiota and the host through signaling from both microbial metabolites and surface molecules leads to development and maturation of healthy immunoregulation. Lessons from animal models have provided some insights into critical signaling pathways activated by metabolites or by microbial associated molecular patterns signaling through conserved pattern recognition receptors. Although there are likely multiple signaling pathways, it is conceivable that signaling through a limited number of conserved pathways are required for induction of healthy immunoregulation in the young host. Vaginal delivery and breast milk likely confer or reinforce these key signaling pathways.