Human milk miRNAs respond to infections of the mother and infant during breastfeeding

Abstract

miRNAs have been recently discovered in different mammals milk. Specifically, human milk (HM) is highly rich in miRNAs, with differential expression amongst its fractions including cells, fat, and skim milk. Various factors, such as the stage of lactation or milk removal during breastfeeding have been shown to influence the miRNA content of HM. Here, we sought to determine the effect of maternal and/or infant infection on the miRNA profile of HM cell and fat fractions analyzed using next generation sequencing. Breastfeeding mother/infant dyads (n=18) were followed during one or more infection episodes as well as upon recovery. HM cells and fat together contained 1,780 known miRNA species, which is the highest number of known miRNAs assayed in human body fluids to date. In addition, 592 novel miRNAs were predicted, of which 95 were of high confidence. Comparisons between samples collected when the participants were healthy and when infected yielded 453 differentially expressed (p<0.05) known miRNAs. Of these, 70 were highly expressed and differentially regulated during infection, with 62 upregulated and 8 downregulated known miRNAs during infection. Most of the highly and differentially expressed miRNAs are known to play critical roles in immunity and immune system development. These findings support the use of HM miRNAs as biomarkers of the health status of the lactating breast and the breastfeeding mother/infant dyad.