Can Genetically Modified Plants Help to Make Infant Formula as Nutritious as Breast Milk?

New research could help close the nutritional gap between infant formula and human breast milk. The study shows how plants can be programmed to produce a broad spectrum of beneficial sugars that are also found in human breast milk. The results could lead to healthier and more affordable infant formula or more nutritious non-dairy plant milks for adults.

A Significant Step Towards Better Infant Nutrition

Globally, the majority of infants – around 75% – consume formula in the first six months of life, either as a sole source of nutrition or as a supplement to breastfeeding. While infant formula is an important food for growing babies, it cannot currently mimic the full nutritional profile of breast milk. This is partly because human breast milk contains a unique blend of around 200 prebiotic sugar molecules that help prevent disease and promote the growth of healthy gut bacteria. However, most of these sugars are difficult, if not impossible, to produce.

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. In a new study published in the journal Nature Food, the study team reprogrammed the plants’ sugar production machinery to produce a variety of these lactose sugars, also known as oligosaccharides. The results could lead to healthier and more affordable infant formula or more nutritious non-dairy plant milks for adults.

The study’s lead author, Patrick Shih, assistant professor of plant and microbial biology and researcher at UC Berkeley’s Innovative Genomics Institute, explains that plants are phenomenal organisms that take sunlight and carbon dioxide from the atmosphere and make sugars from it. And they don’t just make one sugar, but a whole range of simple and complex sugars. We thought, since plants already have this underlying sugar metabolism, why don’t we try to redirect it to make oligosaccharides for human milk?”

Plants that Produce 11 Known Human Milk Oligosaccharides

All complex sugars – including the oligosaccharides of human milk – are made from building blocks of simple sugars, called monosaccharides, which can be linked together to form a variety of chains and branched chains. What makes human milk oligosaccharides so unique are the specific linkages, or rules for connecting simple sugars, found in these molecules. To convince plants to produce oligosaccharides from human milk, the first author of the study, Collin Barnum, manipulated the genes for the enzymes that make these specific linkages. In collaboration with Daniela Barile, David Mills and Carlito Lebrilla from UC Davis, he then inserted the genes into the plant Nicotiana benthamiana , a close relative of tobacco. The genetically engineered plants produced 11 known human milk oligosaccharides as well as a variety of other complex sugars with similar linkage patterns.The researchers produced all three major groups of human milk oligosaccharides.

Barnum then worked to create a stable line of N. benthamiana plants that were optimized to produce a single oligosaccharide from human milk called LNFP1. LNFP1 is a five monosaccharide long oligosaccharide from human milk that is said to be highly beneficial, but so far cannot be produced on a large scale using conventional methods of microbial fermentation.

Currently, a small handful of oligosaccharides can be produced from human milk using genetically modified E. coli bacteria. However, isolating the beneficial molecules from other toxic by-products is a costly process, and only a limited number of infant formulas contain these sugars in their blends. As part of the study, Shih and Barnum, along with Minliang Yang of North Carolina State University, estimated the cost of producing oligosaccharides from plants on an industrial scale and found that it would likely be cheaper than using microbial platforms.

“Imagine if you could make all the oligosaccharides in human milk in a single plant. Then you could just chop up that plant, extract all the oligosaccharides at once and put them directly into infant formula,” Shih said. “There would be many challenges in implementation and commercialization, but that’s the big goal we want to work towards.”