Abstract
Human milk (HM) is rich in miRNAs, which are thought to contribute to infant protection and development. We used deep sequencing to profile miRNAs in the cell and lipid fractions of HM obtained post-feeding from 10 lactating women in months 2, 4, and 6 postpartum. In both HM fractions, 1,195 mature known miRNAs were identified, which were positively associated with the cell (p = 0.048) and lipid (p = 0.010) content of HM. An additional 5,167 novel miRNA species were predicted, of which 235 were high-confidence miRNAs. HM cells contained more known miRNAs than HM lipids (1,136 and 835 respectively, p<0.001). Although the profile of the novel miRNAs was very different between cells and lipids, with the majority conserved in the cell fraction and being mother-specific, 2/3 of the known miRNAs common between cells and lipids were similarly expressed (p>0.05). Great similarities between the two HM fractions were also found in the profile of the top 20 known miRNAs. These were largely similar also between the three lactation stages examined, as were the total miRNA concentration, and the number and expression of the known miRNAs common between cells and lipids (p>0.05). Yet, approximately a third of all known miRNAs were differentially expressed during the first 6 months of lactation (p<0.05), with more pronounced miRNA upregulation seen in month 4. These findings indicate that although the total miRNA concentration of HM cells and lipids provided to the infant does not change in first 6 months of lactation, the miRNA composition is altered, particularly in month 4 compared to months 2 and 6. This may reflect the remodeling of the gland in response to infant feeding patterns, which usually change after exclusive breastfeeding, suggesting adaptation to the infant’s needs.
Highlights
MiRNAs are small non-coding RNA molecules, typically ~22 nucleotide long, that have emerged as crucial regulators of gene expression at the post-transcriptional level [1]
All the mapped and clean reads were annotated to the different RNA types in the to Genebank and RFam to identify and remove rRNA, tRNA, snoRNA, snRNA, scRNA and repeat small RNAs (Fig 1D). miRNAs and unannotated total reads were used for doi:10.1371/journal.pone.0152610.g001
Most of the highly expressed known miRNAs were commonly found in both cell and lipid Human milk (HM) fractions, suggesting that these miRNAs originate from the lactocyte [32], and they are protected within the cells and fat globules to resist digestion in the infant’s gastrointestinal tract [24]
Summary
MiRNAs (or microRNAs) are small non-coding RNA molecules, typically ~22 nucleotide long, that have emerged as crucial regulators of gene expression at the post-transcriptional level [1] They perform this function by binding on the mRNA during translation to either repress it or cause mRNA degradation [2]. Accumulating evidence is suggesting that, similar to plant food-derived miRNA [20, 21], bovine milk miRNA survive the gastrointestinal tract, enter the bloodstream, and exert tissue-specific regulatory functions in the adult [17, 22,23,24] These effects are thought to be mediated by the packaging of milk miRNA in exosomes as well as in milk cells and other microvesicles, which protect them from degradation and facilitate their cellular absorption [7, 25,26,27,28,29]. MiRNAs as a bioactive component of HM are still largely unexplored
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