SRP098835 PRJNA362610 PRJNA361504 PRJNA362601 Early supplementation of human milk oligosaccharides suppresses spontaneous autoimmune diabetes in NOD mice later in life Exclusive and prolonged breast-feeding is known to be an independent protective factor against development of type 1 diabetes (T1D). Aside from reducing exposure to diabetogenic risk factors such as the introduction of cow’s milk and wheat proteins in early life, human milk per se provides bioactive components. Human Milk Oligosaccharides (HMOS) have been demonstrated to be immune modulatory, attenuating development of allergies, reducing susceptibility to infections, therefore have been suggested to be critical in health benefits of human milk. 3. However, little has been known about the direct effects of HMOS on the development of T1D. 4. Here we show that HMOS prevents NOD-mice from developing T1D. 5. Early dietary supplementation of HMOS significantly reduced urine and blood glucose levels, and attenuated pancreatic insulitis severity in NOD-mice later in life. These effects were associated with direct alterations of intestinal microbial metabolites and composition, leading to immunomodulation suppressing the overall immune activation and development of T1D. 6. Our results demonstrate that HMOS are important in the protection of children at risk for T1D. 7. The obtained knowledge on individual specific HMOS may help improve optimal formula for infants who cannot be provided with human milk for any reasons. mouse gut metagenome