In recent years, medical research has revealed how important the microbes in our gut are to our health. It would therefore be interesting to thoroughly unravel the interplay between microbes and body cells. Bjørn Koch made a good start by developing a versatile model to study that interplay. In Nature Communications he described how the gut microbe community affects the immune state of the host.
A start in overhearing the communication between our gut bacteria
‘From the moment in evolution that multicellular organisms arose, they co-evolved with a community of associated microbes. We are therefore host to trillions of microbial guests, making up our microbiome, and they impact all facets of our health’, Bjørn Koch says. ‘Until now, our scientific interest has mainly been focused on potentially pathogenic microbes, not on the hundreds or thousands of commensal species in the microbiome, which are either innocent or helpful. However, it would be valuable to know them better too. Which of these species, most of which live in the gut, contribute to our health and in what ways are they beneficial?’
To find out, scientists need to unravel the molecular mechanisms underlying the communication between these guests and host cells - but that is no easy job. The gut microbiome is complex. Once it is established, it is hard to change its composition, which makes it difficult to manipulate it in experiments in order to dissect the effect of individual microbe species.
However, Koch found a way out. Zebrafish larvae start their life without any microbes living inside. Only when, after hatching, the larvae open their mouths, they are colonised by a microbe community. Koch had noticed that at the time of colonisation, the expression of certain genes in gut cells changes. He realised that zebrafish embryos could be a proper model to study how host cells and microbes exchange signals during and after colonisation, as it is possible to control the colonisation process in zebrafish larvae.
He decided to focus on effects of colonisation on the innate immune system, which is well developed in the embryos as a defence against pathogenic microbes and which is highly similar to that of mammals.
After raising germ-free embryos in a sterile environment, their intestinal immune state was compared to that of embryos that became colonised in the conventional way by a complex microbiome. As expected, colonisation proved to affect the immune state, changing the relative presence of two types of immune cells in the gut: macrophages and neutrophils. In a germ-free intestine, macrophages dominate the intestinal microbe population, but after colonisation, their number decreases and the number of neutrophils increases. Koch: ‘The two immune cell types have different functions, but we cannot tell yet what consequence this shift has.’
To get a clue as to the underlying cause of the shift, he compared the expression of genes in germ-free and in colonised zebrafish embryos. He found different expression levels for many genes. Most remarkable was the down-regulation of the gene that encodes Myd88, a protein in zebrafish which has a defensive function. When receptors – proteins on cell surfaces – detect a pathogenic microbe, Myd88 will often be the first link in transducing the signal to the cell nucleus, where genes involved in defence will be activated. ‘We didn’t expect to find that this essential protein would be down-regulated when commensal microbes colonise the gut - but it is, and the defensive responses are clearly affected by it.’
‘This is a promising start in unravelling the interplay between commensal microbes and the host’, Koch says. ‘Our model is flexible: it is possible to introduce single bacterial species instead of the complex natural community, enabling researchers to profoundly study what happens during colonisation.’
Bjørn Koch (1984, Denmark) studied Molecular Biology at Aarhus University. He moved on with a PhD project focusing on the presence and activity of certain enzymes - chitinases - in zebrafish gut. These enzymes are involved in the digestion of food and the defence against pathogenic organisms. For that research, he spent a year in Leiden. He liked both the research group and the city so much that, after graduating, he returned on a post-doc position in 2014 and performed several projects.