Research on the intestinal microbiome at KU FOOD – health and disease
At the Department of Food Science at the University of Copenhagen (UCPH FOOD), research is being conducted into the gut microbiome ("gut flora") in relation to both health and disease. A lot of what we eat the body cannot immediately break down. We are therefore dependent on the ability of our gut microbes, to degrade food for us so that we can extract the energy.
Understanding the gut microbiome is essential to understand foods and the nutritional potential of food in the body as well as to understand how the interaction between our diet and gut microbes affects health and disease. The microbes in our gut are also important for the "education" of our immune system, just as they protect us from disease-causing micro-organisms, produce different vitamins and convert components from our diet into bioactive substances.
Around 2005 scientific interest in the gut microbiome vastly increased as it was found that imbalance in the intestinal microbiome are implicated in a number of diseases such as overweight, metabolic syndrome, type-2 diabetes, type-1 diabetes and inflammatory bowel disease and many more.
Without understanding the gut microbiome and its function, we will lack an in-depth understanding of how food affects humans. In other words, if we want to understand the impact it has on us humans when we put a meal or food together, we need to know what the intestinal microbiome means for health and disease.
We know that short-chain fatty acids such as acetate, propionate and butyrate play an essential role in our health. For example, propionate is involved in our sense of satiety, i.e. when the intestinal microbiome produces a lot of propionate, then through various receptors and immune signalling, we will feel satiety for longer. Butyrate acts as nourishment for our epithelial cells, so if the micro-organisms in one's gut produce a lot of butyrate, the epithelial cell layer is more "dense", and there is better control over which substances move from the gut to the bloodstream. Acetate is absorbed through the epithelial cell layer into the bloodstream and typically covers about 10% of our daily energy needs. Both acetate, propionate and butyrate are produced by our gut microbes, primarily from indigestible carbohydrates from our diet, for example, plant fibres.
Bacteriophages are viruses that attack bacteria. We largely have as many bacteriophages in our intestines as we have bacteria, and they are quite specific in the sense that a bacteriophage attacks a small specific group of bacteria. These bacteriophages can be extracted and characterised and used to manipulate the gut microbiome. In other words, mixtures of bacteriophages can be used to "push" composition of the microbiome and thus influence host phenotype. We have shown in animal studies that if we put mice on a high-fat diet and give them bacteriophages from mice that are on a low-fat diet, then the mice do not develop metabolic syndrome, a pre-stage to type-2 diabetes, which they normally would develop when on a high-fat diet for a long time. Others have shown that bacteriophages can be used to kill a bacterium that plays a major role in the development of alcoholic hepatitis (a liver disease) and thus prevents or delay the disease from developing.
Probiotics are defined as live micro-organisms that when ingested in adequate amounts confer a health benefit for the host. A challenge with respect to many types of probiotics is to ensure the survival of probiotics before ingestion and during the passage of the upper part of the gastrointestinal tract. As long as probiotics are stored very cold, they are quite stable, but as soon as the microorganisms are stored at room temperature - e.g. in a shop or in a food product, they will often die. After ingestion the probiotics have to pass the stomach, an environment characterized by low pH, which often kills them. It is, therefore, a challenge to maintain probiotics in a state, where in they can reach the desired position in the body and exert the desired effect. At UCPH FOOD, we have worked with various food matrices, e.g. chocolate, where we have incorporated freeze-dried bacteria. It provides an extremely good shelf life of traditional types of probiotics such as various bifidobacteria and lactobacilli. The increased understanding of which micro-organisms characterise a healthy and stable intestinal microbiome has led to a great interest in developing so-called "next-generation probiotics". One challenge with these micro-organisms is that they typically do not tolerate oxygen. We have therefore developed techniques to encapsulate, e.g. the bacterium Akkermansia muciniphila in chocolate. Among other things, type-2 diabetes patients often have a fairly low level of Akkermansia muciniphila,, and apparently, this bacterium is important for sealing the intestinal barrier. The good thing about chocolate is that there is very low water activity, and the bacterium remains inactive. In the stomach, the chocolate fat protects the bacterium from the low pH in the stomach. This allows the bacterium to reach the site of action (the small intestine or colon) in a viable state. And then it is very easy to get people to eat chocolate.
The composition of the gut microbiome is extremely complex. Furthermore, it is very expensive to carry out studies in humans, and although animal models provide many possibilities, the use of experimental animals should be limited as much as possible, so that we only use them for studies where there is no other option. We have therefore developed artificial models (in vitro models) of both the stomach/small intestine and colon. These models can be used to study, e.g. survival of probiotics, examine the effect of different dietary components on the composition of the gut microbiome, or study interactions between disease-causing micro-organisms and, for example, bacteriophages.
A normal intestinal microbiome consists of 100-200 different bacteria, while across many humans, there are more than 10,000 different bacteria. Some of these bacteria are markedly different, while others are largely the same in terms of what they want, can, and do. The bacteria communicate with each other and the outside world - for example, the human they inhabit by metabolising or transforming organic molecules. In order to understand the role of bacteria in food digestion and health, it is necessary to analyse both which bacteria are present, what they are able to do and what they actually produce. DNA analyses are used to identify which bacteria are present, but also which genes they harbour, and thus which enzymes they produce. In addition, metabolome analyses are used to map which metabolites and in what concentrations are present. The coupling of all this data is done through multivariate-pattern recognition techniques that are widely used for image recognition and email spam filters, but also microbiome-metabolome analyses. When the technique is used in biological systems, it is called bioinformatics and chemometrics.
Rasmussen, T.S.; Mentzel, C.M.J.; Kot, W.; Castro-Mejía, J.; Zuffa, S.; Swann, J.; Hansen, L.H.; Vogensen, F.K.; Hansen, A.K.; Nielsen, D.S. (2020). Faecal virome transplantation decreases symptoms of type-2-diabetes and obesity in a murine model. Gut, in press (doi: 10.1136/gutjnl-2019-320005)
Castro-Mejía, J.L.; O'Ferrall, S.; Krych, Ł.; O'Mahony, E.; Namusoke, H.; Lanyero, B.; Kot, W.; Nabukeera-Barungi, N.; Michaelsen, K.F.; Mølgaard, C.; Friis, H.; Grenov, B.; Nielsen, D.S. (2020). Recovery of gut microbiota in Ugandan children administered with probiotics(Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) during treatment for severe acute malnutrition. Gut Microbes, 20:1-13 (doi: 10.1080/19490976.2020
Jakob Stokholm, Martin Blaser, Jonathan Thorsen, Rasmussen, Morten, Johannes Waage, Rebecca Vinding, Ann-Marie Schoos, Asja Kunø, Nadia Fink, Bo Chawes, Klaus Bønnelykke, Asker Brejnrod, Martin Mortensen, Waleed Al-Soud, Søren Sørensen, and Hans Bisgaard. Maturation of the gut microbiome and risk of asthma in childhood. Nature Communications, 1(9):141, 2018
If you want to know more about our research on the intestinal biome and related health effects,
contact professor Dennis Sandris Nielsen (dn@food.ku.dk) and associate professor Morten Arendt Rasmussen (mortenr@food.ku.dk)
Dennis Sandris Nielsen