Experiments by researchers in Zurich showed mice pups without the ability to produce a particular miRNA did not absorb the particles when fed milk from mice containing the miRNA. The team tested tissues in the stomach and intestines, as well as liver, spleen and blood plasma, and found negligible evidence of absorption, concluding the miRNA was digested in the intestine.
The study makes particular reference to two recent studies, by Zhang et al. in 2012, showing absorption of plant miRNA, and by Baier et al. in 2014, demonstrating absorption from cow milk. The Zurich team say both their work and other research have shown such absorption from external, or exogenous, sources, is not likely.
MicroRNAs are short segments of RNA which are themselves non-coding – do not contain information to create proteins – but which regulate how an organism’s genes create proteins. Some microRNAs also play a role in “silencing” certain genes in plants and animals.
“The concept of miRNA regulation from distant cells within the same organism and potentially even from different organisms has led to the question of whether miRNAs from exogenous sources such as food could affect gene expression in human tissues,” the authors wrote.
“While uptake of nutritionally derived miRNAs was originally demonstrated in 2012, this notion has since been rejected by multiple studies demonstrating that miRNAs originating from dietary sources, crossing the intestinal barrier, and regulating gene expression exogenously is highly unlikely.”
In order to test miRNA absorption, the researchers bred knockout (KO) mice lacking the ability to express miR-375 and miR-200c/141 microRNA particles, both of which are found in abundance in mouse milk.
They then bred pups from the KO mice and wildtype (WT) mice, and switched the pups at birth, so WT mice suckled KO pups – giving them milk with miRNAs they could not produce by themselves.
“Systematic analysis of miRNA-KO pups fed WT milk has revealed an absence of detectable miRNA uptake from milk, despite the presence of high copy numbers in milk,” the authors concluded.
“While it remains possible that a small level of uptake does occur and that our methods are simply not sensitive enough to detect it, it is unlikely that such a low copy number would be sufficient for canonical miRNA function. It is thus most plausible that milk miRNAs serve primarily as a nutritional source of nucleic acids for the rapidly growing offspring.”
Source: The Journal of Biological Chemistry
Published online ahead of print, doi: 10.1074/jbc.M115.676734
“Uptake and function studies of maternal milk-derived microRNAs”
Authors: A. C. Title, R. Denzler and M. Stoffel