Around the world, the majority of babies (approximately 75%) take infant formula in their first six months of life, either as the sole source of nutrition or as a complement to breastfeeding. But while formula provides essential nourishment for growing babies, it currently does not replicate the full nutritional profile of breast milk.
This is in part because human breast milk contains a unique blend of approximately 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 modified plants can help close this gap.
In a new study published today in the journal Nature food, the study team reprogrammed the plants’ sugar-making machinery to produce a wide range of these human milk sugars, also called human milk oligosaccharides. The findings could lead to a healthier, more affordable formula for babies, or a more nutritious non-dairy plant milk for adults.
“Plants are these phenomenal organisms that take sunlight and carbon dioxide from our atmosphere and use them to make sugars. And they make not just one sugar, but a whole diversity of simple and complex sugars,” said the lead author of the study, Patrick. Shih, assistant professor of plant and microbial biology and researcher at UC Berkeley’s Innovative Genomics Institute. “We thought, since plants already have this underlying sugar metabolism, why don’t we try to divert it to produce oligosaccharides from human milk?”
All complex sugars, including human milk oligosaccharides, are made from simple sugar building blocks, called monosaccharides, which can link together to form a wide range of chains and branched chains. What makes human milk oligosaccharides unique is the specific set of bonds, or rules, for connecting the simple sugars found in these molecules.
To convince plants to produce oligosaccharides from human milk, the study’s first author, Collin Barnum, engineered the genes responsible for the enzymes that form these specific bonds. Working with Daniela Barile, David Mills and Carlito Lebrilla at UC Davis, he then introduced the genes into the Nicotiana benthamiana Plant, close relative of tobacco.
The genetically modified plants produced 11 known oligosaccharides from human milk, along with a variety of other complex sugars with similar bonding patterns.
“We produced the three major groups of human milk oligosaccharides,” Shih said. “To my knowledge, no one has ever demonstrated that these three groups can form simultaneously in a single organism..“
Barnum then worked to create a stable line of N. benthamiana plants that were optimized to produce a single human milk oligosaccharide called LNFP1.
“LNFP1 is a five-monosaccharide human milk oligosaccharide that is supposed to be really beneficial, but so far it can’t be produced at 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 these larger, more complex human milk oligosaccharides, we could solve a problem that the industry currently can’t solve.”
Currently, a small handful of human milk oligosaccharides can be made using genetically modified E. coli bacteria. However, isolating beneficial molecules from other toxic byproducts is an expensive process and only a limited number of baby formulas include these sugars in their blends.
As part of the study, Shih and Barnum worked with collaborator Minliang Yang of North Carolina State University to estimate the cost of producing human milk oligosaccharides from plants on an industrial scale and found that it would likely be cheaper than using microbial platforms. .
“Imagine being able to produce all the oligosaccharides in human milk in a single plant. Then you could just grind that plant, extract all the oligosaccharides simultaneously, and add them directly to infant formula,” Shih said. “There would be a lot of challenges in implementation and commercialization, but this is the big goal we’re trying for. where to move forward.”
Additional 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 US Department of Energy, and the National Center for Complementary and Integrative Health (R00AT009573)