Marcel de Zoete

Think big and follow your gut

“It may sound cliché, but during my years in the USA I’ve learned not to be afraid to think big. At Yale, the motto was: if you can choose, why not spend your time on something that has the biggest impact on science and health? At the same time, I believe it’s very important to not let impact factors be too much of a guide and simply follow your own gut. My main interest has always been bacterial pathogens of the intestinal tract—Helicobacter pylori, Salmonella Typhimurium, Campylobacter jejuni and the last 5 years the more pathogenic members of the microbiota.

The microbiota revolution
One of the most exciting breakthroughs in recent biology is the ‘discovery’ of the intestinal microbiota and the impact it has on all of us — both during health and disease. As the field is young and rapidly evolving, numerous important questions still need to be answered. I am always interested in mechanism; how does it work? Particularly in the microbiota field this is important since many studies done so far are mostly descriptive without going into details. These details are exactly what we focus on in my group.

Crossing barriers
When we moved back to The Netherlands after almost 5 years abroad, I received a NWO Vidi grant to continue my work on the role of the microbiota in health and disease. We now start to realize that for many inflammatory disorders, only a small number of bacterial species seem to really make the difference. These are the bacteria that live very close to the epithelial cells of the intestinal tract. I always picture it as the earth: everything that is far off in outer space doesn’t generally pose much danger, but everything that is able to reach the earth’s atmosphere—in the gut represented by the inner-most protective mucus layer that overlays the cells in the intestine—can lead to serious problems.

Fascinating complexity
The complexity of the microbiota and the difficulties to study it mechanistically pose great challenges but also make for an extremely fascinating subject. The majority of the bacteria in the gut have never been studied before, in part because it is very hard to grow them outside of the intestinal tract. We’re getting better and better in creating suitable growth conditions in the lab by using specialized growth media in combination with an absolute absence of oxygen. For this we have had a large anaerobic chamber installed that has less than 0.0001% oxygen and closely mimics the conditions inside the gut.

Manipulating the microbiota in humans and animals
When we have a clearer understanding of the ways the microbiota influences the host, we can take the next big step: manipulating the intestinal microbiota in order to benefit health. While much of the attention still goes to human research, these fundamental breakthroughs will undoubtedly have great value for veterinary health as well. In addition, many bacterial pathogens are zoonoses and infect us through contact with infected animals. Whether this also holds true for pathogenic members of the microbiota remains to be determined, but there is no reason to think that these bacteria cannot be transferred from the animal to the human host. While it’s clear that there are still many challenges ahead, it’s good to see that microbiology is fully back in the spotlight!"