Swammerdam Institute for Life Sciences
Focus on research: molecular microbiologist Jeroen Hugenholtz
Jeroen Hugenholtz has been affiliated with the University of Amsterdam since May 2006 as professor of Industrial Molecular Microbiology for one day per week. He investigates how you can get lactic acid bacteria to do more than just produce tasty yoghurt.
Hugenholtz hasn't actually worked in a lab for a long time. Besides his professorship, he works as Principle Scientist Food Fermentations at NIZO Food Research (Nederlands Instituut voor Zuivelonderzoek, the Netherlands Institute for Dairy Produce Research). He is also allied to TI Food & Nutrition at Wageningen, and vice-director of ‘The Kluyver Centre for Genomics of Industrial Fermentation'.
'By combining these positions with my professorship, I am able to carry out fundamental research that is not directly industry-driven, while the fact that I am a professor has its advantages for NIZO,' says Hugenholtz, laughing. He admits that it is rather difficult to build something up from scratch in only one day a week. However, in cooperation with research institutes in Norway, Germany and England, he recently set up a European project: a comparative study of three different lactic acid bacteria. ‘These bacteria are very successful in their own surroundings: in food, in the intestine and as pathogens. We want to find out why they are so successful in their various environments and whether we are able to influence this. To do so, we are developing a mathematical model that describes precisely what these bacteria do.'
‘In the past it seemed an illusion to think it possible to model something so complicated. Nowadays genomics technology enables us to take ever more precise measurements of all sorts of processes, making it seem possible to create a descriptive and, moreover, a predictive model. We think we will be able to do this for lactic acid bacteria because it is a relatively simple, one-cell organism strongly oriented to converting sugar into lactic acid as quickly as possible.' Hugenholtz' aim is to describe all the steps in the bacteria's metabolism. ‘If you can describe this extremely precisely, you will then be able to use the model to predict what happens if you make any alterations. This requires a lot of calculation because, although this cell is a simple organism, it still comprises many different components. We are now close to a model of the complete cell.'
Hype?
Lactic acid bacteria are used in most fermentation processes. Hugenholtz investigates how he can change and improve the fermentation process. ‘I investigate how you can use lactic acid to make a product taste better, improve its digestibility or make it healthier.' Development of a probiotic (=health-promoting) product requires a lot of research. A first step is to isolate the various lactic acid bacteria in a healthy person's intestines. These bacteria are then cultivated and we subsequently investigate whether they are able to survive a low pH environment such as that of the stomach. ‘The bacteria that survive best are cultivated in large amounts and added to foodstuffs. Using volunteers or test animals, tests are taken to see whether the products have the desired effects. This method has resulted in quite a number of new cultures that have an explicit health-promoting effect.'
According to advertisements, the one milk product with bacteria supplement is healthier than the next. ‘It is, of course, partly a hype', admits Hugenholtz. ‘If a product works properly and sells well, all manufacturers want to have their own version of the product. But probiotics won't disappear. The world is becoming more and more interested in the nutritional value of food, and probiotics play a large role here.' Hugenholtz can understand a certain suspicion with regard to probiotics. ‘In the beginning, not so very long ago, it was still possible to print all sorts of claims on the packaging and in that period there were, perhaps, products on the market that were unable to live up to what they promised. Nowadays, fortunately, legislation requires that you are able to prove what you claim on your packaging in controlled studies. Probiotics are not a hype, research still continues and is perhaps even increasing.'
Vitamin factories
Hugenholtz has been directing research for almost twenty years. ‘One of the nicest results was being able to make genetic alterations to lactic acid bacteria such that they acted completely differently. For example, we made a bacteria that produced enormous amounts of the taste component di-acetyl - butter aroma. It has a dominant odour that can be smelled throughout the whole lab. And recently we were successful in modifying lactic acid bacteria to produce large amounts of vitamins, thousands of times the normal amount of folic acid (vitamin D), riboflavin (B2) and cobalamin (B12); these vitamins are relevant for your daily vitamin requirements. If is, thus, possible to use lactic acid bacteria to produce specific components of your own choice, and this is rather spectacular!'
Hugenholtz' vitamin factories have not yet been used as food additives. ‘Genetically modified micro-organisms are very successful but have not, however, been introduced in Europe. Not because they are not allowed, but because industry doesn't want to: they are afraid that the consumer won't like it.' Hugenholtz uses his findings with regard to modified bacteria to make bacteria more productive in a natural manner. ‘The increase is then less spectacular, but it still has its value for all sorts of applications in the food industry.'
America versus Europe
Homologous recombination, whereby only genetic material from the organism itself is used for modification, is not viewed as being genetic modification in America, and does not need to be labelled as such. ‘We could introduce our lactic acid bacteria on the American market. It would be rather disappointing to have to do so, since our biggest supporters are Dutch companies and institutes. But we are certainly considering this option.'
‘In Europe it is possible to take a culture, irradiate it with UV light in order to see whether mutants are formed with the properties you are interested in. This is a standard technique in the fermentation industry, whereby alterations are being made continuously, but you cannot be sure exactly what has been changed. You see only one effect, but other changes could occur that you don't know anything about that may have far-reaching consequences. The rules are such that these are considered as natural variants and they may, thus, be used as food additives. Whereas when you make genetic modifications, you know exactly what you are changing; we are completely in control as far as this type of bacteria is concerned. This is rather frustrating for a scientist, and I think it is very short-sighted.'
Ultimate model
Nevertheless, Hugenholtz remains motivated and never loses sight of his main goal: a mathematical model of lactic acid bacteria. ‘I am working on all sorts of processes and subjects, but my main aim is to create a mathematical model for lactic acid bacteria, and I am confident that I will succeed in doing so.'