Weighted Epigenetic Profiling of Milk miRNAs Across Human, Bovine, and Camel Species: A Comparative Global Score

Milk microRNAs (miRNAs) are key mediators of maternal–offspring communication, potentially influencing postnatal development through systemic epigenetic regulation. While miRNAs in human and bovine milk are extensively studied, the regulatory landscape of camel milk remains underexplored despite its unique therapeutic reputation. In this study, we conducted a comparative cross-species analysis of miRNA targets from human (Homo sapiens), bovine (Bos taurus), and camel (Camelus dromedarius) milk. To estimate regulatory impact, we implemented the Global Score, a weighted metric integrating quantitative miRNA abundance with thermodynamic binding affinity (miRWalk 2.0), cross-validated by multi-algorithm statistical consensus via mirDIP 5.2.Analysis revealed distinct species-specific miRNA concentration strategies: human milk maintains a highly diversified "regulatory symphony" (90% mass distributed across 35 miRNAs), while camel milk utilizes a "biological intervention" strategy, with only 12 miRNAs constituting 90% of the pool and miR-148a exerting extreme dominance (61.8%). A conserved regulatory core (Common All) was identified, accounting for over 80% of the total regulatory weight, primarily associated with neuroplasticity and MAPK/Ras signaling.Camel milk miRNAs displayed a distinctive therapeutic signature, uniquely targeting pivotal immune and metabolic nodes, specifically STAT3 (linked to Th17 cell differentiation) and PPARD, providing a molecular basis for its reported anti-inflammatory and anti-diabetic effects. Conversely, human milk showed high-confidence human-specific targeting of NLGN3, essential for synaptic organization. Bovine milk exhibited a significantly closer functional alignment to the human "epigenetic template" (14.8% shared genes) than camel milk (1.5%), particularly in pathways maintaining genomic stability (e.g., XPO1). These findings demonstrate that milk miRNAs operate through both a universal developmental backbone and specialized regulatory environments, offering a comparative framework for applications in clinical nutrition and precision medicine.