Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells

Abstract

Our results for the first time reveal the survivability and complexity of human milk exosome microRNAs upon simulated gastric/pancreatic digestion, and the dynamics during lactation stages. The results suggest a previously underexplored area of infant response to genetic material in human milk exosomes.

Milk MicroRNAs in Health and Disease

“…The first study focusing on milk microRNAs was only reported in 2010 (Hata et al., ; Kosaka et al., ) and opened a very new field of research focused on milk microRNAs. From then on, a number of studies have focused on investigating milk microRNAs profiles in various conditions including mammary gland infections (Sun et al., ), breast cancer (Do Canto et al., ; Gu et al., ; Pigati et al., ), lactation periods (Hou et al., ; Na et al., ; Xi et al., ), milk processing (Howard et al., ; Oh et al., ), and digestion (Benmoussa et al., ; Kahn et al., ; Liao, Du, Li, & Lonnerdal, ).…”

“…Among those, the same microRNAs are recurrently found in the top 10 most enriched sequences in milk (Table ). Most interestingly, in all the studies, these 10 microRNAs represent 40% to 80% of all sequences suggesting that, depending on the sample, a limited number of microRNA is specifically secreted in milk (Golan‐Gerstl et al., ; Kahn et al., ; Liao et al., ; Munch et al., ; Rubio et al., ; Simpson et al., ; van Herwijnen et al., ; Zhou et al., ).…”

“…It is then with little surprise that this microRNA is the most studied milk microRNA (Benmoussa et al., ; Golan‐Gerstl et al., ; Melnik, ; Melnik & Schmitz, , ; Simpson et al., ; van Herwijnen et al., ). Other less‐expressed microRNAs have nevertheless been investigated in breast milk, like the immunity‐related microRNAs hsa‐miR‐223 or hsa‐miR‐146a (Iannaccone et al., ; Liao et al., ; Perri et al., ; van Herwijnen et al., ).…”

Literature review of baseline information on non‐coding RNA (ncRNA) to support the risk assessment of ncRNA‐based genetically modified plants for food and feed

“…Immunerelated miRNAs expression is reported to be higher in colostrum than mature milk (Izumi et al, 2012;Na et al, 2015). In vitro studies of human milk miRNAs using either RNase digestion, freeze-thaw cycles, low pH or other GI conditions have shown that these miRNAs are relatively highly stable (Kosaka et al, 2010;Liao et al, 2017). Similarly high stability of miRNAs was found when using one or all of the above mentioned hard conditions for milk from cow (Hata et al, 2010;Izumi et al, 2012), pig (Gu et al, 2012 or panda .…”

“…In vitro studies using miRNAs isolated from breast milk exosomes, either human or bovine, were found (Liao et al, 2017), and CRL1831, K562 or Lim1215 (Golan-Gerstl et al, 2017). When subjected to proteinase K treatment or when the vesicle structure was destroyed, uptake or transport of these exosomal miRNAs was compromised (Kusuma et al, 2016;Wolf et al, 2015;Sun et al, 2013).…”