HMOs recreated in plants, and not just for babies

Breast milk contains a specific group of around 200 prebiotic sugars known as human milk oligosaccharides (HMOs). These sugars are very important for the developing infant, especially in the development of their microbiota. However, they are often absent from baby formula.

A new study​ from the journal, Nature Food, has managed to develop HMOs from plants. If used commercially, the method in this study could have the potential to provide HMOs for a healthier formula for babies.

Beyond their use in baby formula, there are, researcher Patrick Shih told FoodNavigator, emerging markets for adult HMO use. For example, they are currently being studied for their potential to treat irritable bowel diseases, improve intestinal barrier function and lower gastrointestinal inflammation.

Why is producing HMOs important?​According to the study, 75% of babies worldwide drink baby formula in their first six months of life. However, most infant formulas are either devoid of, or only contain one or two, HMOs.

Sugar terminologyMonosaccharides – ​Monosaccharides are the simplest form of sugar and cannot be hydrolysed (broken down) into smaller subunits.

Oligosaccharides – ​Oligosaccharides, which include HMOs , are short chains of simple sugars. They typically contain between three and nine monosaccharides, have been linked to prebiotic benefits​.

Polysaccharides – ​Polysaccharides are complex carbohydrates formed of long chains of simple sugars, usually at least ten.

HMOs are extremely important for infant development, establishing the gut microbiota, supporting growth and preventing diseases.

They are, however, very difficult to replicate in commercial baby formula. Currently, for example, it can be produced using E. Coli bacteria, although isolating the beneficial molecules from toxic byproducts is costly, and only a limited number of HMOs can be produced using this method. Certain companies, such as dsm-firmenich​, have also produced some HMOs as an ingredient.

However, the current study has been able to produce HMOs not from bacteria, but plants. HMOs developed using this method, believe the researchers, could be a whole lot cheaper than producing them using microbial platforms. This is largely because of the latter’s low yields.

Furthermore, plants are capable of producing a range of HMOs that are not currently developable through microbial platforms. Thus, plants can provide researchers with access to previously inaccessible HMOs.

How did the researchers develop HMOs? ​Plants, Shih suggested, are the perfect source of sugars, as they already use carbon dioxide and sunlight to create them. The researchers just needed to rerout their ability to create sugars into creating HMOs through a molecular farming process. 

All sugars are made of monosaccharides, or simple sugars. The key to creating HMOs is creating the right set of linkages between different monosaccharides.

LactoferrinLactoferrin is another component​ often found in human milk in abundance, at 1.4mg/ml. It not only helps babies absorb iron, but also acts as an antimicrobial and antiviral agent.

In order to instruct plants to make the right linkages, study first author Collin Barnum engineered the genes responsible for the enzymes that make the linkages which make up HMOs. He then introduced them into the Nicotiana benthamiana plant (which is closely related to tobacco).

These genetically modified plants were able to create 11 known HMOs, as well as other sugars with similar complex linkage patterns.

Following this, Barnum created a stable line of N. benthamiana plants which were optimised to create an HMO called LNFP1.

What is LNFP1?​LNFP1 is a five-monosaccharide-long HMO. So far, producing LNFP1 has been difficult, especially with microbes, which has meant that its health affects have been difficult to study. But the research helps move along this process.

“LNFPI is a complex oligosaccharide so there are challenges in its biosynthesis,” Shih told us. “The innate sugar metabolism of plants help with the production of LNFPI.”

The ability for the researchers to produce LNFP1 specifically was promising, as it showed the potential to make specific HMOs.

Sourced From: Nature Food
‘Engineered plants provide a photosynthetic platform for the production of diverse human milk oligosaccharides’
Published on: 13 June 2024
DOI: https://doi.org/10.1038/s43016-024-00996-x
Authors: C. R. Barnum, B. Paviani, G. Couture, C. Masarweh, Y. Chen, Y. Huang, K. Markel, D. A. Mills, C. B. Lebrilla, D. Barile, M. Yang & P. M. Shih