Late-Breaking: Non-nutrient Factors in Colostrum: Systems Biology of Mammary Derived Bioactive Proteins and Gut Receptors That Network Functions in the Bovine Neonate

Abstract Maternal-offspring coevolution has introduced the biological concept of “neonatal programming,” in which soluble proteins of varying abundance in bovine colostrum can have targeted activities in the calf gut. Still, the identities and developmental programming mechanisms of the full profile of colostrum proteins on transiently expressed gut receptors/transporters, as well as the ultimate functional responses in the calf, remain to be completely elucidated. The objective of this study was to address this gap in knowledge using systems biology. First, we biopsied the mammary gland and examined the transcriptome in primiparous and multiparous Holstein cows (at parturition/day 0 contrasted to 40–50 days after parturition; n = 4–5/group; FDR< 0.05) and used a bioinformatics algorithm to delineate transcripts coding proteins destined to be secreted into colostrum. In parallel, we analyzed the neonatal small intestine (0 day-old contrasted to 7 day-old; n = 3–5/group; FDR< 0.05) to identify transcripts that code for membrane receptors/transporters precise to the period of colostrum consumption. Integrative analysis of these results highlighted 44 possible signaling circuits (cutoff: >10 nCPM) directed by colostrum in the neonatal gut, providing a consolidated predictive understanding of colostrum-mediated effects that might occur in the neonate during this crucial period in development. These findings also represent the first mechanistic insight into mammary-sourced components that target the neonatal gut to regulate aspects of postnatal development that encompass intestinal maturation, gut-based secondary signaling, and establishment of the gut microbiome, all relevant to long-term health and development. Towards applications, these results are poised to offer novel opportunities to enhance commercial supplements via biomimicry to better reflect the physiology supporting neonatal growth and development.