Loss of nutritionally relevant microRNAs in cow milk–based infant formulas compared with raw camel and buffalo milk reveals molecular and functional disparities

Milk-derived microRNAs (miRNAs) have attracted increasing attention due to their involvement in regulation of biological processes. However, the degree to which these molecules are conserved in infant formulas remains unclear. Herein, a high-throughput small RNA sequencing was performed to reveal the profile of miRNAs from camel milk, buffalo milk, and commercial infant formulas. Compared with raw milk, infant formulas exhibited significant reductions in miRNA diversity and abundance. Camel and buffalo milk were enriched in development- and immune-related miRNAs, comprising let-7, miR-2887, miR-2904, and miR-1246, whereas formulas reserved limited subsets at lower levels. Functional enrichment analysis indicated that raw milk–derived miRNAs were involved in immune-associated pathways, signifying conserved functions in immune regulation across species. Although both camel and buffalo milk display immunological significance through miRNA-facilitated gene regulation, camel milk miRNAs seem to target a broader spectrum of pathways, including those involved in cellular interactions and viral defense. Furthermore, protein–protein interaction analysis for the highly expressed miRNA targets identified central regulatory hubs such as HLA, LILRB1, LIN28B, and TUT4, involved in RNA processing, immunity, and stem cell maintenance. This study could offer a molecular foundation to support the expansion of next-generation infant formulas that more effectively retain functional RNA components of raw milk.