Maternal-infant transfer of microbial modified immunity - PROJECT SUMMARY/ABSTRACT Maternal leukocytes can migrate to an infant not only during pregnancy via the placenta, but also after delivery via breastfeeding. Immune cells in the milk have a significant heterogeneity, and they include innate cells [macrophages, neutrophils, natural killer cells] and adaptive [T and B] cells. The immature adaptive immune system needs education by the mother to facilitate immune tolerance and responsivity. A specific probiotic (Limosilactobacillus reuteri DSM 17938) has been examined in our laboratory and found to have anti-inflammatory effects in several disease models, including neonatal necrotizing enterocolitis (NEC), Treg-deficiency-induced autoimmunity (IPEX syndrome in humans), and in a mouse model of multiple sclerosis. Recently, we found that orally feeding DSM 17938 could modify the function of circulating Tregs. When probiotic- educated Tregs were adoptively transferred to newborn pups exposed to experimental NEC, probiotic-educated Tregs were more potent than naïve Treg cells at reducing inflammatory T cells. A current knowledge gap our understanding of how probiotics modify microbes, interact with leukocytes, and express metabolites that may be transferred from mother to infant to benefit early life immunity. The specific aims are to (1) characterize probiotic-modulated immune transfer from mother to infant. We will use mice with congenic markers to distinguish immune cells arising from mother and infant. We will gavage feed DSM 17938 to pregnant and lactating dam to identify the transfer of immunity from mother to infant via (via the placenta or breast milk) by studies of the cross-fostered newborn pups; and we will (2) assess the potentially beneficial effect of transferring probiotic-modulated immunity from mother to infant in the setting of Treg- deficiency-induced autoimmunity. In both aims, dynamic changes of stool microbiome and metagenome and plasma probiotic-modulated metabolites in the mother and infant will be determined.
