Deep milk: comprehensive multi-omics to resolve the role of human breastmilk in type 1 diabetes risk

The increasing incidence of type 1 diabetes (T1D) in the past few decades, especially in young children, speaks to a role for environment and early life exposures [1]. Infant feeding practices may be contributing to childhood risk of T1D. Breastmilk is a complex, optimal source of nutrition for infants, the components of which vary depending on maternal characteristics driven by both genetics and the environment [2, 3]. Breastfeeding has a profound and long-lasting impact on the development of the infant immune system through the provision of bioactive substances (e.g., oligosaccharides, immunoglobulins, hormones, growth factors etc.) and beneficial bacteria (Lactobacillus, Bifidobacterium, and Firmicutes) that support a healthy microbiota [4-6]. Studies have shown a difference in the gut microbiome between children with islet autoimmunity (IA) or T1D and healthy children [7-9]. Previous studies exploring relationships between breastfeeding and T1D risk have been contentious with discrepancies across different meta-analyses, as recently reviewed [4]. Studies examining breastmilk composition at the omics level in relation to T1D risk have not been performed. It is unclear whether breastmilk bioactives, rather than just breastmilk consumption, are driving protection against T1D as well as the mechanisms by which this protection may be afforded. Moreover, the influence of maternal T1D on breastmilk composition is not known and whether this could be contributing to “maternal protection” in the inheritance of T1D risk. The ‘ENDIA’ pregnancy-birth cohort study of children at-risk for T1D represents a unique opportunity to study the role of breastmilk in IA/T1D progression. Our specific hypotheses (Figure 1) are:
• Both the breastmilk microbiome and breastmilk bioactives within the lipidome, metabolome and glycome are associated with the risk of IA.
• The maternal diet modulates breastmilk composition, thereby providing an opportunity for intervening in the T1D risk pathway.
• Maternal T1D alters breastmilk composition in ways that may be relevant for protection for the infant.