Metabolomics and bioactive substances
The most objective mapping of cell state
Metabolomics is an effective and exploratory tool for analysing cell metabolites in humans, animals and plants.
Metabolites are low-molecular substances resulting from the metabolism or detoxification of nutrients or when nutrients are used for synthesis of other molecules which the cell needs.
All living cells excrete metabolites when exposed to external influences from, e.g., foods, pollution and environmental conditions.
By analysing the metabolites, researchers in LIFE's elite research area can obtain a 100% objective picture of how humans, animals and plants respond to the surrounding world.
We have asked anchorperson Professor Søren Balling Engelsen eight sharp questions about the elite research area:
• Where is research within metabolomics and bioactive substances currently heading as a field?
• How does LIFE contribute worldwide to the research within metabolomics and bioactive substances?
• Which other promising research projects would you like to mention?
• If the elite research area becomes the success you are hoping for in the coming years, what do you hope to achieve?
• How will LIFE students benefit from the elite research area?
• What are your considerations in relation to collaborating with companies, authorities or others that may have a particular interest in this specific elite research area?
• Where can you follow the elite research area’s results?
• Who is behind the elite research area?
Anchorperson Søren Balling Engelsen:
– Research in metabolomics, which is an explorative technique like genomics, started in the 1990s based on new analysis techniques.
The research area is also an effective and holistic tool for analysing metabolites in cells, plants, animals, humans or in the environment.
You study, e.g., the total molecular content of a cell at a given time, i.e. the entire composition, physiology and dynamics of the cell.
All living cells, both in animals, plants and humans, change the way they produce and excrete metabolites when exposed to external influences from foods, nutrients and environmental conditions. Which nutrients are excreted depends to a large extent on the cell's genes, but also the environment.
Assumption-free exploration
What is so special about metabolomics is that the method can be used exploratively, which means that we can examine a sample without knowing beforehand what we are looking for.
We can explore plants, animals, humans or foods and create completely new knowledge. The analysis method also provides an entirely objective picture of the state of the organism.
The research field has been made possible by the development of analytical equipment such as nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography mass spectroscopy (LC-MS) and the development of high performance computers and software for data processing.
Metabolomics research can be divided into two main areas: plants and humans
Metabolomics research can roughly be divided into plant metabolomics and nutrimetabolomics.
Plants being the focal point, metabolomics research will, e.g., investigate whether you can prevent the production of a toxin (a metabolite) in a plant by mutating a gene responsible for its production.
You may also study a plant for its beneficial health effect and then try to concentrate the beneficial substance (a metabolite).
Researchers have succeeded in developing sorghum plants which do not produce cyanogenic glucosides and barley mutants having an increased content of beta-glucan, a healthy dietary fibre.
Nutrimetabolomics focuses on human response to foods. An example of a project in this field could be an intervention study in which a group of test subjects are given a bioactive substance from a plant to map the metabolic effect in addition to the more traditional disease risk markers.
Algorithms find patterns and translate incomprehensible measurement results
When 'fingerprinting' the metabolome in a plant or a blood sample, NMR or LC-MS provides us with an extremely detailed but also complex result with thousands of signals from the total set of metabolites.
Most of the signals are incomprehensible, and we therefore need to use pattern recognition.
Using mathematical algorithms we try to find underlying patterns which can translate the signals, e.g. to generate knowledge about how the test subjects' lifestyle affect their immune system, risk of developing diseases etc.
Huge data volumes still a bottleneck
Despite having access to state-of-the-art equipment, we are still struggling with huge data volumes that need to be analysed. Data processing has become a bottleneck in metabolomics studies.
There are plenty of reasons for saying that metabolomics research opens up for assumption-free exploration.
We take many samples, compare them with others and obtain new information. We then develop algorithms capable of translating data into information and new knowledge.
Metabolomics is actually one of the only ways to make an objective statement about the health potential of foods.
One way of doing this is to give some of the nutrition study participants a diet containing blueberries and others the same diet without blueberries and subsequently test their blood samples to map any differences.
The new knowledge obtained may in future be used for developing new dietary recommendations, and sometimes it will also be possible to obtain information that can be used to tailor the advice to certain population groups or individuals.
Helping combat obesity
Metabolomics is also a promising tool when it comes to combating and preventing obesity.
We and other researchers are, e.g., studying whether there are some special biomarkers of obesity or differences between those individuals who are able to maintain a weight loss and those who cannot, in other words whether there are metabolites in the blood that determine whether you develop obesity or not.
We are also studying whether weight loss may be affected by certain bioactive dietary components or through new diet combinations. In this context, metabolomics helps us find the underlying explanations by mapping key changes in the metabolite pattern.
– Along with our colleagues at the University of Copenhagen, LIFE is a world leader within certain areas of the field and we are thus making important contributions to international metabolomics research.
Considering some of the other elite research areas at LIFE, it is therefore a little surprising that metabolomics is still called an 'emerging' elite research area.
The nuclear magnetic resonance (NMR) spectroscope funded by the Danish Dairy Research Foundation in 2003 has since been supplemented by state-of-the-art equipment with superconducting magnets.
This means that in addition to studying substance structures, we are now also able to read the metabolite patterns of an organism. We used to spend a week analysing a single sample, but now we can analyse hundreds of samples every day.
Healthy diets tailored to different population groups
We have recently started a major EU project to develop inexpensive and healthy diets adapted to the poor regions in Europe. The project will study the human metabolome in large groups of poor and rich individuals in Denmark, Italy and the UK. The project is an excellent reflection of the explorative characteristics of metabolomics.
Using urine samples from the test subjects, we will test whether humans in risk of poverty (ROP) have any specific underlying patterns.
We would like to try to provide an average picture of the state of the organism in both rich and poor individuals.
It is important that the study is explorative. The study may, e.g., reveal that the metabolism of poor Italians is generally healthier than that of rich Britons or vice versa.
It will be really exciting to see the outcome, and once we have an overview of the results, we will be helping to develop new, healthy food products specifically capable of correcting any imbalance in the dietary habits of the rich and the poor.
The hunt for early cancer markers
In another project conducted in collaboration with the Danish Cancer Society, we are screening blood and urine samples from more than 3,000 individuals who have donated samples to the Danish Cancer Society.
We know that a small proportion of those having provided blood samples have developed cancer. We are using this knowledge to identify early markers – is there anything in the blood to indicate that you will develop cancer in future? This is also a very explorative approach, and, yet again, free of assumptions. We have already screened the 3,000 blood samples and have just started our data analysis.
Drought-resistant wheat
Within plants, we are also working on making wheat drought-resistant. We start by doing mass mutations. Then we take plant extract samples to study the chemical fingerprints of the plant mutations using metabolomics.
We are studying whether some of the wheat mutants can increase the plant's drought resistance. The most promising plant mutations are subsequently tested in cultivation studies.
There is a global desire to use metabolomics to increase and optimise the biofuel potential of rape. In this way, the areas allocated to biofuels can be reduced without impacting the yield.
New medicines to be found in the plant kingdom
Metabolomics is also an exciting area when it comes to producing future medicines. Many medicines originate from plants, so by exploring plants by means of metabolomics you may discover novel bioactive substances as has been the case with the cancer-inhibiting glucusinolates in broccoli.
The Center for Biosustainability at the Technical University of Denmark (DTU) has been granted DKK 700 million for a new major initiative, where a research group from LIFE will perform metabolomics on a number of different medical plants to identify the synthesis routes and the genes responsible for producing complex diterpenoids having a cancer-inhibiting effect.
These substances are extremely complex and cannot (or only with great difficulty) be produced by chemical synthesis. This makes bioproduction competitive in terms of prices.
Individualised diet based on your DNA
Finally, I would like to mention the perspectives of our research in terms of planning an individualised diet. The fact of the matter is that one bioactive substance may work very well in some individuals, but be totally ineffective in others.
That is why broccoli protects some individuals against diseases, while it has no effect in others. At individual level, metabolomics can map whether a given bioactive substance is effective or not.
So if you want to plan and adapt a certain diet to a population group, you can phenotype people, i.e. subdivide the population into categories based on their DNA and identify unique genes which determine which type of diet you need the most.
But identifying a bioactive substance and linking it to a body function is not an easy task. Sometimes we succeed. It has, e.g., been documented that caffeine increases the blood pressure in individuals with a specific genotype, whereas dietary fibres make it drop in practically all humans.
We are currently conducting a research project where we measure chylomicrons in the blood, i.e. the large particles in the blood transporting particulate fat in lymph and blood immediately after intestinal absorption.
LIFE has just patented this, and we are establishing a partnership with the NMR instrument producer BRUKER.
Here, we are studying how and how quickly fat is absorbed in the body depending on your diet, e.g. a Nordic diet or a Mediterranean diet.
– Then we will, among other things, have identified some new biomarkers, e.g. in plants, thus helping us find and document new bioactive substances.
It would also be a major breakthrough to identify some early cancer markers. This may potentially save many lives as it allows you to take relevant measures and perhaps prevent the development of cancer.
We are also hoping to succeed in producing advanced biomedical substances using green plant factories. In addition, our impact factor is on the rise, a development we very much hope to continue.
– The elite research area will ensure continued world-class research in advanced multivariate data analysis and plant bioactive substances in the coming years.
As LIFE offers research-based teaching, our students will get access to the most recent knowledge in the area. PhD schools will also be established for interdisciplinary collaboration within metabolomics.
– It is our ambition that the research within the elite research area will result in the emergence of small, new businesses producing bioactive substances with documented health recommendations.
The vanillin project with Evolva A/S is an example of what the future will bring in other areas.
– At LIFE's website, www.models.life.ku.dk, and in international scientific journals. We are also creating a website for the elite research area where you will soon be able to follow our projects.
Who is behind the elite research area?
- Professor Søren Balling Engelsen
- Professor Birger Lindberg Møller
- Professor with Special Responsibilities Lars Ove Dragsted
- Professor with Special Responsibilities Søren Bak
- Professor with Special Responsibilities Dan Stærk
Kirsten Jenlev, - last update:18 November 2011