MicroRNAs from colostrum and mature cow milk: High-throughput sequencing and functional enrichment

As vital regulators of newborn development, milk-derived microRNAs (miRNAs) have gained increasing attention recently. However, the variation in miRNAs profile among colostrum and mature milk remains unclear. We hypothesized that miRNAs content of colostrum and mature cow milk differs significantly, reflecting stage-specific biological functions related to immune priming and metabolic adaptation. Herein, high-throughput small RNA sequencing was performed to compare miRNAs profile in colostrum and mature cow milk. A total of 353 and 390 miRNA precursors were respectively detected in colostrum and mature milk, with diverse expression profiles. Colostrum displayed higher quantities of immune-related miRNAs, such as <i>let-7</i>, <i>miR-21</i>, and <i>miR-146</i>, whereas mature milk was enriched in metabolic regulation-related miRNAs, such as <i>miR-29b</i>, <i>miR-210</i>, and <i>miR-378</i>. Differential expression analysis showed 159 miRNAs substantially upregulated in colostrum and 38 in mature milk. Functional enrichment and pathway analysis revealed that mature milk miRNAs were associated with energy metabolism and tissues remodeling, while colostrum miRNAs were involved in early immune signaling and developmental activities. These findings support our hypothesis that miRNA expression patterns are temporally controlled across lactation and may serve as molecular indicators of milk functionality. This knowledge could be leveraged to enhance newborn nutrition strategies and design functional dairy products enriched with stage-specific miRNAs.