A new study may have solved an ongoing debate about the benefits of ingesting microRNA molecules from food or liquid. The molecules appear to suppress cancer cell growth and may play a role in obesity and diabetes.
Results from a 2011 study with rice and a more recent study with cow’s milk seemed to support the idea of creating functional foods based on microRNAs, and using them to regulate physiological processes in the human body. However, a new study with mice raises doubt that microRNA can survive the digestive system.
Experiments led by Markus Stoffel, a biology professor at ETH Zurich, show the dietary uptake of microRNAs is barely significant, and certainly insufficient to affect physiological functions. Moreover, the microRNA molecules are broken down in the small intestine.
Stoffel used two families of mice to conduct the study. One descended from a standard race of laboratory mice (the so-called wild type), while the other consisted of mice in which a specific microRNA molecule had been knocked out.
The molecule in question goes by the name of miR-375 and is normally produced in the pancreas, the intestine and the mammary glands. It is one of the microRNA molecules found in high concentrations in maternal milk.
Foster Mothers' Milk
The scientists allowed the two mouse families to reproduce, but exchanged their offspring immediately after birth. In this way, the researchers were able to conduct their experiments on juvenile mice that did not express miR-375 but were suckled by a female whose milk contained miR-375.
When the researchers examined the stomach milk content of the juvenile mice raised in this way, they found high concentrations of miR-375.
“MicroRNA molecules are relatively resistant to gastric acids,” explains Stoffel.
On the other hand, they only found minute traces of miR-375 in other parts of the body. The concentrations they measured were at least a thousand times lower than the level needed to regulate gene expression and thereby modify physiological and metabolic processes.
In particular, the researchers detected nothing more than the slightest concentrations of miR-375 in the cellular lining of the small intestine.
This is relevant because all digested food has to pass through this barrier before entering the bloodstream. Furthermore, analysis of the blood and the liver provided no evidence of the presence of miR-375.
“We can only assume that the microRNAs are broken down into smaller components by the enzymes in the gastrointestinal tract,” says Stoffel.
In a laboratory experiment in which milk containing miRNAs is mixed with digestive juices present in the small intestine the researchers proved that this is indeed the case. But if microRNAs in maternal milk are broken down before they enter the bloodstream of the suckling infant, what is the benefit? Stoffel says the answer may be simple:
Babies grow rapidly and to do so they need RNA building blocks in addition to the many other nutrients that promote cell growth. These components are produced in the small intestine by the digestive processes that break down microRNAs from the mother’s milk.
“It is reasonable to conclude that these components are quite simply there to nourish the infant,” adds Stoffel.
Alexandra C. Title, Remy Denzler and Markus Stoffel Uptake and function studies of maternal milk-derived microRNAs J. Biol. Chem. jbc.M115.676734. doi:10.1074/jbc.M115.676734
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