Worldwide, a majority of babies (approximately 75%) drink infant formula during the first six months of life, either as a sole source of nutrition or as a supplement to breastfeeding. But while bottle feeding provides essential nutrition for growing babies, it does not currently replicate the full nutritional profile of breast milk.
That’s partly 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, most of these sugars remain difficult, if not impossible, to manufacture.
New research led by scientists at the University of California, Berkeley and the University of California, Davis, shows how genetically engineered plants can help close this gap.
This is evident from a new study published today in the journal Natural foodthe research team reprogrammed plants’ sugar production machinery to produce a wide range of these human milk sugars, also called human milk oligosaccharides. The findings could lead to healthier and more affordable formula for babies, or more nutritious non-dairy plant-based milk for adults.
“Plants are phenomenal 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 whole variety of simple and complex sugars,” says senior author Patrick. Shih, assistant professor of plant and microbial biology and researcher at UC Berkeley’s Innovative Genomics Institute. “We thought: since plants already have an underlying sugar metabolism, why not try to redirect it to make oligosaccharides from breast milk?”
All complex sugars – including oligosaccharides from breast milk – are made of building blocks of simple sugars called monosaccharides, which can be linked together to form a wide variety of chains and branched chains. What makes breast milk oligosaccharides unique are the specific set of links, or rules, for connecting simple sugars together found in these molecules.
To convince plants to make oligosaccharides from breast milk, first author Collin Barnum engineered the genes responsible for the enzymes that make these specific links. Working with Daniela Barile, David Mills and Carlito Lebrilla at UC Davis, he then introduced the genes into the Nicotiana benthamiana plant, a close relative of tobacco.
The genetically modified plants produced eleven known oligosaccharides from breast milk, along with a variety of other complex sugars with similar linking patterns.
“We made all three major groups of oligosaccharides from breast milk,” Shih said. ‘As far as I know, no one has ever shown that you can make all three of these groups at the same time in one organism.“
Barnum then worked to create a stable line of N. benthamiana plants optimized to produce a single breast milk oligosaccharide called LNFP1.
“LNFP1 is an oligosaccharide of five monosaccharides from human milk that should be really useful, but so far cannot be made on a large scale using traditional methods of microbial fermentation,” says Barnum, who completed the work as a graduate student at UC Davis. . “We thought if we could start making these larger, more complex oligosaccharides from breast milk, we could solve a problem that the industry currently can’t solve.”
Currently, a small handful of oligosaccharides can be produced from breast milk using engineered E. coli bacteria. However, isolating the beneficial molecules from other toxic byproducts is a costly process, and only a limited number of baby foods contain these sugars in their blends.
As part of the research, Shih and Barnum worked with colleague Minliang Yang of North Carolina State University to estimate the cost of producing human milk oligosaccharides from plants on an industrial scale. They found that this would likely be cheaper than using microbial platforms.
“Imagine if you could make all the oligosaccharides from breast milk in one plant. Then you could just grind up that plant, extract all the oligosaccharides at the same time and add them directly to infant formula,” Shih said. “There would be many challenges in implementation and commercialization, but this is the big goal we are trying to achieve. to move towards.”
Other authors include Bruna Paviani, Garret Couture, Chad Masarweh, Ye Chen, Yu-Ping Huang, David A. Mills, Carlito B. Lebrilla and Daniela Barile of UC Davis; Kasey Markel of UC Berkeley; and Minliang Yang of North Carolina State University.
This work was supported in part by the National Institutes of Health (NIGMS T32 Training Program), the U.S. Department of Energy, and the National Center for Complementary and Integrative Health (R00AT009573).
