Impact of interspecies colostrum and milk replacement on circulating sncRNA dynamics of neonatal goat kids

Replacing maternal colostrum and milk with those from other species is common practice in neonatal ruminant management, but the effects on small non-coding RNA (sncRNA) transmission remain poorly understood. This study investigated whether colostrum and milk replacement alters circulating sncRNA profiles in neonatal goats using a twin-pair model. Six vaccinated goat dams (Mycobacterium avium ssp. paratuberculosis) and their twelve kids were included. One goat twin kid received maternal colostrum and milk, while the other was fed a replacement diet with bovine colostrum and milk replacer. Small RNA sequencing was performed on serum samples from kids, as well as on goat colostrum and milk and on bovine replacers. All colostrum and milk samples contained diverse sncRNAs, including miRNAs, and tRNA- and rRNA-derived fragments. Processing and storage influenced sncRNA abundance and stability. In neonatal serum, sncRNA profiles changed during development and indicated two response waves: after colostrum replacement and after three weeks of continued milk replacement. These changes involved differential abundance of miRNAs and rRNA-derived fragments, including molecules linked to immune regulation, metabolism, and developmental pathways. Although sequence similarity between bovine and caprine sncRNAs limited direct inference of dietary transfer, the observed differences suggest that milk origin and composition may influence circulating sncRNA profiles. Several milk-associated miRNAs were consistently detected in serum, suggesting potential maternal transfer. Overall, these findings indicate that interspecies milk replacement may modify neonatal circulating sncRNAs, highlighting a potential role for milk-derived sncRNAs in shaping early-life immune and developmental programming.