Differential transcriptomic impacts of breastmilk compared to formula milk

BackgroundBreastmilk confers numerous benefits to infants relative to formula milk, such as promoting metabolic health and supporting immune homeostasis. However, in-depth mechanistic insights comparing the influence of breastmilk versus formula milk across different compartments are lacking. MethodsSeveral datasets interrogating the effects of breastmilk versus formula milk were curated, including transcriptomes of infant intestinal organoids, intestinal gene expression microarray, and single cell RNA-seq data for infant peripheral blood mononuclear cells (PBMCs). Comparative analyses were performed, with a specific focus on differences at a signal pathway level. ResultsComparative analyses revealed that intestinal exposure to breastmilk was linked to elevated gluconeogenesis, as well as reprogramming of other metabolic, nutrient-sensing and immunerelated pathways. Contrarily, in PBMCs, formula milk feeding was linked to upregulation of apoptosis-related pathways across all PBMC subsets. ConclusionsBreastmilk reprograms the transcriptomic landscapes of infant intestine, particularly promoting intestinal gluconeogenesis. This might explain its metabolic advantages via modulating metabolic homeostasis. Different effects were found in PBMCs, where formula milk is linked to enhanced apoptotic signalling in the infants developing immune cell subsets.