Today, it is possible to produce a small number of breast milk oligosaccharides with the help of transgenic E. coli bacteria. However, isolating the beneficial molecules from other toxic products is an expensive process, and only a limited number of infant formulas include these sugars in their mixtures.
Most babies, about 75% worldwide, are fed infant formula in the first six months of their lives, either as a sole source of nutrition or as a supplement to breastfeeding. But while formula provides essential nutrition for growing babies, it currently does not replicate the full nutritional profile of breast milk.
Part of the reason for this is because human breast milk contains a unique blend of about 200 prebiotic sugar molecules that help prevent disease and support the growth of healthy gut bacteria. However, it is still difficult and sometimes impossible to produce most of these sugars.
A new study led by scientists from the University of California at Berkeley and the University of California at Davis shows how genetically modified plants may help close and narrow this gap.
In a new study published in the journal Nature Food, the research team reprogrammed the plants' sugar production system to produce a wide variety of human breast milk sugars, also called breast milk oligosaccharides. The findings may lead to a healthier and cheaper infant formula, or a more nutritious non-dairy plant milk for adults.
"Plants are wonderful organisms that take sunlight and carbon dioxide from our atmosphere and use them to make sugars. And they don't just make one sugar - they make a wide variety of simple and complex sugars," said senior study author Patrick Shea, associate professor of plant and soil biology and agriculture in the Faculty of Plant and Agricultural Sciences at UC Berkeley and a researcher at UC Berkeley's Institute for Innovative Genomics. "We thought, since plants already have this basic sugar metabolism, why don't we try to redirect it to produce breast milk oligosaccharides?"
All complex sugars - including breast milk oligosaccharides - are made from building blocks of simple sugars, called monosaccharides, which can be linked together to form a wide variety of chains and branched chains. What sets the oligosaccharides of breast milk apart is the special bond sets, or rules, for connecting simple sugars together found in these molecules.
To make plants produce breast milk oligosaccharides, first study author Colin Barnum engineered the genes responsible for the enzymes that make these special bonds. Working with Daniela Barilla, David Mills and Carlito LaBarilla of the University of California, Davis, he inserted these genes into the Nicotiana benthamiana plant, a relative of tobacco.
The genetically engineered plants produced 11 known breast milk oligosaccharides, along with a variety of other complex sugars with similar linkage patterns.
"We made all three major groups of breast milk oligosaccharides," Xia said. "To my knowledge, no one has shown that all three of these groups can be produced simultaneously in a single organism."
Barnum then worked on creating a stable line of Nicotiana benthamiana plants that were adapted to produce a single breast milk oligosaccharide called LNFP1.
"LNFP1 is a breast milk oligosaccharide, five monosaccharides long, that should be very beneficial, but until now it could not be produced on a large scale using traditional microbial fermentation methods," said Barnum, who completed the work as a graduate student at UC Davis. "We thought that if we could start producing the larger and more complex oligosaccharides of breast milk, we could solve a problem that industry currently cannot solve."
Today, it is possible to produce a small number of breast milk oligosaccharides with the help of transgenic E. coli bacteria. However, isolating the beneficial molecules from other toxic products is an expensive process, and only a limited number of infant formulas include these sugars in their mixtures.
As part of the research, Xia and Barnum worked with associate Minliang Yang of the University of North Carolina to estimate the cost of producing breast milk oligosaccharides from plants on an industrial scale and found that it would likely be cheaper than using microbial platforms.
"Imagine that you could produce all the oligosaccharides of breast milk in one plant. Then you can simply grind the plant, extract all the oligosaccharides at once and add them directly to infant formula,” said Shea. "There will be many challenges in implementation and commercialization, but this is the big goal we are trying to move towards."
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