Xenobiotic tracers uncover the neonatal gastrointestinal passage, cellular uptake and Ago2 loading of milk miRNAs in neonates

Whether milk microRNAs might vertically transmit signals for neonatal development or not remains an outstanding question with clinical implications. Deep-sequencing revealed that mammals have in common a significant number of milk miRNAs yet exhibit taxon-specific milk miRNA fingerprints. We could trace intact bovine-specific microRNAs from formula-nutrition in human preterm stool and 9 days after the onset of enteral feeding in intestinal cells of a preterm piglet model. Few hours after the introduction of enteral feeding with reporter microRNA-supplementation (cel-miR-39-5p/-3p), we observed enrichment of this xenobiotic microRNA in blood serum and in Ago2-immunocomplexes from intestinal biopsies. This points to a relevance of milk microRNA signals. We performed Adenovirus type 5-based microRNA-gene transfer into human primary intestinal epithelial cells and examined predicted bta-miRs targets on the protein and transcriptome levels. Results suggest that milk microRNAs could influence the expression of human genes in intestinal epithelia of neonates under special conditions in vitro.