New research published in Nature Food reveals a groundbreaking development in infant nutrition: the successful production of human milk oligosaccharides (HMOs) in plants. This exciting discovery could pave the way for large-scale, affordable production of these vital nutrients, potentially transforming the infant formula industry and offering significant health benefits to infants worldwide.
For decades, scientists have recognized the critical role human milk oligosaccharides (HMOs) play in infant health and development. These complex sugars, naturally present in breast milk, act as prebiotics, selectively nourishing beneficial bacteria in the infant gut. This fosters a healthy microbiome crucial for digestion, immune system development, and overall well-being.
However, replicating the intricate complexity of HMOs in infant formula has proven challenging. While approximately 200 distinct HMO structures exist in human milk, current formula production methods have only achieved commercial viability for a handful of simple HMOs. This limitation has driven researchers to explore alternative production platforms, leading to this groundbreaking research utilizing plants as biofactories for HMOs.
This study, conducted by a team of researchers from the University of California, Berkeley, and the University of California, Davis, focused on leveraging the inherent carbohydrate-producing capabilities of plants to generate a diverse range of HMOs.
How did they do it? Let’s delve into the science behind this remarkable feat.
Plants, being masters of sugar production through photosynthesis, possess a natural ability to synthesize complex carbohydrates. The researchers harnessed this innate potential by introducing genes from bacteria known to produce HMOs into the Nicotiana benthamiana plant, a relative of tobacco commonly used in plant research. This genetic modification enabled the plants to produce the necessary enzymes for HMO biosynthesis within their cells.
The results were astounding.
The modified plants successfully produced all three major classes of HMOs found in human milk:
- Neutral HMOs: These form the core structures of more complex HMOs. The researchers successfully produced lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), two major neutral HMOs in human milk, along with larger neutral oligosaccharides with varying degrees of complexity.
- Fucosylated HMOs: These HMOs, decorated with fucose sugar molecules, are the most abundant class in human milk. The team achieved significant production of 2′-fucosyllactose (2′FL) and lacto-N-fucopentaose I (LNFPI), the two most prevalent fucosylated HMOs. Notably, LNFPI, despite its abundance in breast milk, has been challenging to produce via microbial fermentation, making this achievement even more significant.
- Acidic HMOs: Characterized by the presence of N-acetylneuraminic acid, these HMOs provide unique biological activities. The researchers engineered the plants to produce CMP-Neu5Ac, a precursor molecule not naturally found in plants, enabling them to generate a range of acidic HMOs, including 6′-sialyllactose (6′SL) and sialyllacto-N-neotetraose c (LSTc).
This research marks the first time a single heterologous organism has been able to produce such a diverse array of HMOs.
The team didn’t stop there. Recognizing the need for commercially viable production, they focused on optimizing the production of LNFPI, a complex fucosylated HMO, in plants. By strategically manipulating the plant’s nucleotide sugar biosynthetic pathways, they were able to significantly enhance LNFPI production, demonstrating the potential for tailoring plant systems for optimal HMO yield.
To confirm the functionality of these plant-derived HMOs, the researchers conducted in vitro studies using Bifidobacterium longum subsp. infantis (B. infantis), a beneficial bacterium known to thrive on HMOs in the infant gut. Remarkably, the plant-produced HMOs exhibited the same selective growth-promoting effects on B. infantis as HMOs isolated from human milk, indicating their potential prebiotic efficacy.
This discovery has the potential to revolutionize the infant formula industry.
Currently, commercial HMO production relies heavily on microbial fermentation, which faces limitations in producing complex HMOs at scale and cost-effectively. This new research suggests that plants could offer a more sustainable and scalable platform for producing a wider variety of HMOs, potentially leading to more affordable and readily available HMO-fortified infant formulas.
Furthermore, the researchers conducted a technoeconomic analysis comparing plant-based HMO production with existing microbial platforms. The results indicated that producing LNFPI in plants, particularly when integrated into a biorefinery system for coproduction with biofuels, could be significantly more cost-effective than microbial methods.
What does this mean for the future?
While further research and development are needed to optimize plant-based HMO production and assess its scalability for commercial application, this study presents a promising avenue for improving infant nutrition globally.
Imagine a future where all infants, regardless of breastfeeding access, can benefit from the health-promoting properties of a wider range of HMOs. This research brings us one step closer to that reality, offering a beacon of hope for a healthier future for generations to come.
