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Berkeley, CA – In a groundbreaking study, scientists at the University of California, Berkeley, and the University of California, Davis, have made significant strides toward bridging the nutritional gap between infant formula and human breast milk. Their research, published today in the journal Nature Food, demonstrates how genetically engineered plants could be used to produce human milk oligosaccharides (HMOs), a key component in breast milk that supports infant health but is difficult to replicate in formula.
Globally, about 75% of infants consume formula during their first six months, either exclusively or as a supplement to breastfeeding. While formula provides essential nutrients, it lacks the unique blend of approximately 200 prebiotic sugars found in human breast milk. These HMOs play a crucial role in disease prevention and the growth of healthy gut bacteria in infants.
The research team, led by Patrick Shih, assistant professor of plant and microbial biology at UC Berkeley and investigator at the Innovative Genomics Institute, has reprogrammed the sugar-making machinery of plants to produce these HMOs. “Plants are phenomenal organisms that take sunlight and carbon dioxide from our atmosphere and use them to make sugars,” Shih said. “We thought, since plants already have this underlying sugar metabolism, why don’t we try rerouting it to make human milk oligosaccharides?”
Human milk oligosaccharides are complex sugars made from building blocks of simple sugars called monosaccharides. What makes HMOs unique are the specific linkages between these simple sugars. To reproduce these linkages in plants, study first author Collin Barnum engineered genes responsible for the enzymes that create these specific linkages and introduced them into the Nicotiana benthamiana plant, a close relative of tobacco. The genetically modified plants successfully produced 11 known HMOs and a variety of other complex sugars with similar linkages.
“We made all three major groups of human milk oligosaccharides,” Shih noted. “To my knowledge, no one has ever demonstrated that you could make all three of these groups simultaneously in a single organism.”
Barnum also developed a stable line of N. benthamiana plants optimized to produce a specific HMO called LNFP1. “LNFP1 is a five-monosaccharide-long human milk oligosaccharide that is supposed to be really beneficial, but so far cannot be made at scale using traditional methods of microbial fermentation,” said Barnum, who completed the work as a graduate student at UC Davis. “We thought that if we could start making these larger, more complex human milk oligosaccharides, we could solve a problem that the industry currently can’t solve.”
Currently, only a few HMOs can be produced using engineered E. coli bacteria, but isolating these beneficial molecules from toxic byproducts is costly, and only a limited number of formulas include them. The study’s findings suggest that producing HMOs in plants could be more cost-effective. Collaborating with Minliang Yang at North Carolina State University, the team estimated that producing HMOs at an industrial scale using plants would likely be cheaper than current microbial methods.
“Imagine being able to make all the human milk oligosaccharides in a single plant. Then you could just grind up that plant, extract all the oligosaccharides simultaneously, and add that directly into infant formula,” Shih said. “There would be a lot of challenges in implementation and commercialization, but this is the big goal that we’re trying to move toward.”
The research, supported by the National Institutes of Health, the U.S. Department of Energy, and the National Center for Complementary and Integrative Health, represents a promising step toward making infant formula more closely resemble the nutritional profile of human breast milk, potentially leading to healthier infants worldwide.
