Interestingly, one of the miR-21 target genes is the PTEN tumor suppressor. In addition, both miR-192 and miR-215 are tumor suppressors and upregulation of miR-215 inhibits the differentiation of colon cancer stem cells. Therefore, the BAY-60-7550 miRNAs identified in this study have important functions in intestinal disease and contribute to variations in immune function between individuals. Our further studies will aim to investigate the function of candidate miRNAs in intestine epithelial cells by altering their expression and investigating the effect on the immune response to E. coli F18 infection by measuring levels of cytokine secretion and cell surface antigen expression. In addition, an ectopic target reporter gene could be developed to identify E. coli F18-resistant pigs for an improved pig-breeding program. Compared with mature milk, the initial milk is often referred to as colostrum, and is higher in immunological agents and other compounds that act against viruses, bacteria, and parasites. This helps to protect the newborn until its own immune system can function properly. MicroRNAs, an abundant class of evolutionarily conserved small non-coding RNAs of,22 nucleotides that are derived from 70 nt long stem-loop precursors, are post-transcriptional regulators that bind to complementary sequences on target mRNAs, usually resulting in translational repression in mammals. Emerging evidence suggests that miRNAs have important roles in regulating the development of immune cells and in modulating innate and adaptive immune responses. Extracellular miRNAs in various body fluids have recently been shown to be associated with various pathological conditions. These circulating miRNAs are mainly delivered by exosomes, which are membranous vesicles of endocytic origin that are released by a variety of cell types into the extracellular space. Exosomes appear to play a significant role in cellular communication in the immune system and elsewhere by transferring miRNAs, mRNAs, and proteins to neighboring cells. Exosomes are present in human breast milk and are packaged with abundant immune-related proteins, as well as miRNAs, have the potential to influence the immune system of the infant. Here, we present the miRNA expression profiles in porcine milk exosomes across six lactigenous stages. We particularly emphasize the differences between the colostrum and mature milk. We found that , and may have significant effects on the development of the immune system in infants. This study also highlights the use of pigs as a model organism for human breastfeeding medicine and immune diseases research. This study reports the comprehensive lactation-related miRNA expression profiles of porcine breast milk exosomes. We found that immune-related miRNAs are present and enriched in breast milk exosomes and are generally resistant to relatively harsh conditions. These immunerelated miRNAs are present in higher numbers in the colostrum compared with the mature milk or the blood of colostrum-only fed piglets compared with the mature milk-only fed piglets. The presence and enrichment of immune-related miRNAs in breast milk exosomes, especially in the colostrum, was demonstrated. These miRNA-loaded exosomes in breast milk may be transferred into the infant body via the digestive tract. These observations call for further detailed investigations to obtain a thorough understanding of the essential effects of breast milk in the development of the infant’s immune system.