Sweet science

Sugar has a bad name: bad for your teeth, bad for your waistline. But there’s more to sugar than that, says University of Groningen Professor of Microbiology Lubbert Dijkhuizen. He’s spent most of his career working on starches and sugars. ‘For one, as we sit here talking our brains are burning sugar at a high rate. Each process in our body that requires a lot of energy uses sugar as a fuel.’

But that’s not all. As well as basic monosaccharides such as glucose, fructose or galactose, there are sugars made up of a few (oligosaccharides) to many (polysaccharides) sugar units. Many have specific biological functions. ‘Human breast milk contains some 200 different oligosaccharides,’ Dijkhuizen explains. ‘These stimulate the immune system of the baby and act as prebiotics, which means they stimulate the growth of beneficial bacteria in the intestines.’

That’s why manufacturers of infant formula are interested in these healthy sugars. ‘But the problem is we don’t really know how they work – and which specific oligosaccharides have a beneficial effect.’ There are two problems in getting to grips with these sugars. ‘First, these oligosaccharides are often produced as mixtures of different molecules. Second, there are as yet no assays showing which oligosaccharides have a beneficial effect, and their mechanisms of action are largely unknown.’

The Carbohydrate Competence Center (CCC), a centre of expertise in the field of carbohydrates of which Dijkhuizen is one of the founders and which brings together academics and industrial partners, has received EUR 3.6 million to find out why some sugars are beneficial. The project is funded by the ‘Agri&Food’ sector of the Dutch government’s ‘Top Sectors’ programme aimed at stimulating research in nine areas. The funding will enable scientists from several universities and research institutions to work together on this topic with a number of industrial partners.

Dijkhuizen’s group will try to elucidate the structure-function relationship of such oligosaccharides. The linkages between sugar molecules can vary in different ways and in different quantities. Using analytical methods such as mass spectrometry and NMR spectroscopy, they will determine the exact structure of different oligosaccharides. ‘And we really want to know which part of the molecules causes the specific effects of these oligosaccharides.’

At the University Medical Center Groningen (UMCG), tests will be designed to measure the effects of sugars on, for instance, the immune system. This will be done in the lab and in animal models. Wageningen University will focus on the microbiology of the human intestinal tract. ‘We need to know which bacteria live there and what effect specific sugars may have on their growth. It is known, for example, that certain fructose-based or galactose-based oligosaccharides stimulate the growth of beneficial microorganisms like bifidobacteria and lactobacilli.’

In addition, scientists from the TNO research institute will use their ‘artificial gut model system’ to investigate the effects of specific sugars, while the DLO agriculture research institute will look at the way oligosaccharides affect the immune system.

The project is a public-private partnership: Dijkhuizen and his academic colleagues will perform basic research, and the companies that are putting up half of the funding will use this knowledge to improve their products or develop new products. ‘Valorization of research results is therefore an integral part of the project.’

Dijkhuizen has extensive experience in working with industrial partners. ‘Some academics are hesitant about forming partnerships with industry. But we have found that if you make the proper arrangements, you can do excellent basic research in such a setting.’ In recent years the CCC has been successful in acquiring research funds and producing innovative research in public-private partnerships.

So what will the project deliver in its four-year run? Dijkhuizen: ‘We hope to know much more about the structure-function relationships of oligosaccharide prebiotics. We should also have discovered how sugars can stimulate the immune system. And we will have developed tests to ascertain the effect of oligosaccharides on biological systems and the human microbiota.’

This knowledge will help dairy companies produce healthier infant formula. ‘But a feedstock company is also involved. The amount of antibiotics used in animal husbandry must be reduced, and prebiotics in the animals’ food may help keep them healthy.’

As for Dijkhuizen’s own group, a better knowledge of which oligosaccharides are useful will provide the focus for the design and engineering of enzymes that make these specific sugars. ‘Currently, most oligosaccharides are made by forcing hydrolytic enzymes to work in reverse, in the synthetic mode. However, this may result in the synthesis of a whole bunch of different oligosaccharides in a very non-specific way. We see room for improvement here.’

The participants in the project ‘Carbohydrates for improving health’ are Rijksuniversiteit Groningen, UMCG, Wageningen Universiteit & Research , DLO and TNO as research institutions, and FrieslandCampina, Danone, Nutreco, Avebe, Sensus/Royal Cosun and Winclove as industrial partners.

DLO/TNO will contribute EUR 1.8 million in kind by taking on part of the research project. The industrial partners will provide EUR 1.8 million of funding for the basic research performed by the academic partners, and they will also contribute in kind by carrying out work in their own research labs.