Exosomal MicroRNAs in Milk from Mothers Delivering Preterm Infants Survive in Vitro Digestion and Are Taken Up by Human Intestinal Cells

Scope: This study investigates the ability of preterm milk exosomes to survive gastric/pancreatic digestion, internalization by intestinal epithelia, and the microRNAs (miRNAs) contents. Methods and results: At average infant age 1 week and 6 days, milk is collected from mothers who delivered preterm and term infants (n=10). Milk is exposed to conditions simulating infant gut digestion. Exosomes are isolated and lysed, and the exposed miRNAs are sequenced. Preterm milk exosomes survive in vitro digestion, and can be taken up by intestinal epithelia. Three hundred and thirty miRNAs are identified as preterm milk exosome miRNAs, and in vitro digestion does not have a pronounced effect on their expression. The abundant miRNAs in preterm milk exosomes are similar to those from term milk. Twenty-one low abundance miRNAs are specifically expressed in preterm milk exosomes compared to early term milk in the current study and what previously is found in mature term milk. Conclusion: These results for the first time reveal the survivability of preterm milk exosomes following simulated gastric/pancreatic digestion. The authors demonstrate the richness of the miRNAs content in these exosomes. The results improve the knowledge of preterm milk biology and the molecular basis by which exosome miRNAs may uniquely affect preterm infants during early development.