Grant: Project Grant

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin producing beta cells in the pancreas by autoreactive T cells. There is no cure for this disease in spite of decades of research, and individuals afflicted with T1D rely on frequent blood glucose measurements and insulin injections to maintain their blood glucose within a normal range. T1D development is strongly influenced by genetic factors. Interestingly, infants born from mothers with T1D are 2-7 times less likely to develop diabetes, compared to infants with fathers with T1D. This striking observation strongly argue for a protective role of maternal factors in reducing infant T1D risks, that dominate over genetic predisposition. We made similar observations in animal models, where maternal IgA deficiency protected the young from developing T1D. Thus, we set out to explore the mechanisms underlying maternal protection of disease, with the aim to harness them for disease prevention. Notably, we pinpointed the effect to be occuring during the nursing period, and is accompanied by dramatic changes in the bacteria that is in the infant gut, as well as the products that they make. In this proposal, we seek to unravel the bacterial species and products that are mediating maternal protective effects. We will test these species/products for disease preventing activities, and we will study the host vs bacterial cross-talks that occur in the gut to protect against disease.