Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment

Scope This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants. Methods and Results Mature milk is collected from the mothers of term and preterm infants. Using high‐throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let‐7 and miR‐148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR‐3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR‐3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs). Conclusion This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants. This study finds that specifically high expression of miR‐3168 in premature breast milk exosomes affects the proliferation of neural stem cells and is required for neural stem cells to differentiate into neurons.