Associate Professor Henrik Bjørn Nielsen

Gut microbial communities reveal risk of obesity and type 2 diabetes

Tuesday 03 Sep 13
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Henrik Bjørn Nielsen
Associate Professor
DTU Health Tech
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Søren Brunak
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Thomas Sicheritz-Pontén
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Simon Furbo
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Having a particular set of bacteria in your gut places you in the high-risk group for developing metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease. These findings—recently published in Nature—offer the prospect of developing new prevention and treatment strategies.

The number of overweight and obese people is currently increasing by several per cent per annum in many of the industrialized countries. This is why there is now talk of an outright obesity epidemic that represents a ticking time bomb under the healthcare systems of the West. Obesity, however, is not an unequivocal diagnosis. For some people, obesity does not pose a serious health risk—while for others obesity results in dire consequences in the form of metabolic illnesses and increased mortality.

Few species is bad
It is therefore seen as a potential breakthrough that researchers from DTU and Centre for Basic Metabolic Research at the University of Copenhagen—together with a large international research team—have now succeeded in identifying people with an increased risk of developing obesity-related diseases such as type 2 diabetes and cardiovascular disease. Common to this group is the fact that they have certain species of bacteria in their gut that can be used as markers. Generally, they also all have a low richness of bacterial species in their intestinal flora—while healthy people have a high richness of bacterial species and therefore also a high number of microbial genes in the gut. And this is important knowledge, explains DTU researcher Henrik Bjørn Nielsen from Centre for Biological Sequence Analysis, DTU Systems Biology:

“For a long time we have known—from twin studies among others—that obesity and related metabolic diseases aren’t just about lifestyle but also involve an important hereditary component. But proving this has been extremely difficult using particular genes in the human genome. The task is simply too complex. If we look at our metagenome, however—i.e. the quantity of genes from the microorganisms (chiefly bacteria) living in our gut—we have now succeeded in proving a clear link between the presence of certain bacteria and the incidence of metabolic diseases. This gives researchers renewed hope of developing techniques to prevent and treat these diseases.”

Many or few genes
The new results are based on the mapping of 292 Danes’ microbiome (composition of microorganisms in the intestinal system). As most of the bacteria in our gut cannot be cultivated, they have to be studied indirectly by examining which genes are present—and the results show that the vast majority of the study group fell into two categories: Those with less than 480,000 different genes and those with more than 600,000 genes.

Metabolic disorder markers
Thanks to the generally explosive development in DNA sequencing and metagenomics—combined with entirely new methods developed in connection with this research project—it was also possible to demonstrate not only which genes but also which types of bacteria each individual had in his/her gut flora right down to species level. When the researchers then compared the number of bacteria species in the gut with the individuals’ general state of health, the group with a small number of bacterial species had a higher BMI and was more metabolically stressed with diabetes and cardiovascular problems, for example. It also became clear that by screening for a few particular bacterial species it was possible to identify those individuals at high risk of developing metabolic disorders. These findings pave the way for crucial new metabolism research, which is why these new techniques and results are now being published in the distinguished science magazine, Nature.

“In the course of this project we have developed a technique enabling us to identify even unknown bacterial species using gene profiles. Previously, reference genomes of known cultivatable bacteria were used for identification purposes, but now there are sufficient data for us to say with a high degree of certainty that this is a new species by examining which genes they always co occur with (so-called Coabundance). And this is actually a quantum leap for metagenomics research”, explains Henrik Bjørn Nielsen

Early days
Despite the grounds for optimism, Henrik Bjørn Nielsen believes that this type of research is at a very early stage—as there is a great deal researchers still do not know. One of the big questions is why they are seeing a particular pattern in the microbiome of individuals with metabolic disorders.

“What we’re hoping is that it is the microorganisms in the intestine which in some way provoke the metabolic disturbances—because that makes it easier to develop new intervention strategies—but it could just as easily be the opposite—that it’s the inflammation associated with type 2 diabetes that results in a lower richness of bacterial species in the gut.”

Changes over time
The next thing researchers want to study therefore is how the bacterial composition changes over time. “In principle, this study represents a frozen moment in an individual’s life. The next step will be to carry out time studies to map bacterial composition over longer periods to determine how static or dynamic our microbiome actually is and how it is affected during illness. The more we understand about the development of the microbiome in relation to the onset of illnesses such as obesity and type 2 diabetes, the better our chances of intervention and prevention”, concludes Henrik Bjørn Nielsen

About the project
The new knowledge is the result of an extensive international research project financed by the European Commission under the major EU Metahit project, which officially ended in 2012. DTU is one of several Danish and European collaborative partners that also includes The Novo Nordisk Foundation Centre for Basic Metabolic Research at the University of Copenhagen.

Chatelier et al.  Richness of human gut microbial communities correlates with metabolic markers, 29. Aug 2013 Nature, doi:10.1038/nature12506

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