Nearly half a million for unique research into equine digestion

NWO's Open Technology Program is making nearly half a million available for research by Utrecht University and Wageningen University & Research into disturbed intestinal flora in horses. "It is unique that the government and industry are providing so much funding for horse-specific research," says research leader Prof. Dr. Wouter Hendriks.

Digestive problems can have serious consequences for horses, such as inflammation of the hoof wall (laminitis) or colic. However, research into metabolic diseases in horses is often relative invasive. "Our Bacin2Deliver research program brings together several technologies into a single platform that allows scientists to study the enterohepatic (intestine-liver) axis of horses in the lab," says Hendriks. "We can use these technologies to study the effects of feeds in a horse's gastrointestinal tract which is currently difficult. In addition, it is an important step toward an animal-free future for research into these kinds of bodily processes."

From the Faculty of Veterinary Medicine of Utrecht University, in addition to Hendriks, Louis Penning, Ellen Roelfsema, Robin van den Boom and David van Doorn are co-applicants. "We are very happy with this grant," says Van Doorn. "In this research, we connect more fundamental research with the veterinary practice: from cell to clinic. Moreover, it fits perfectly with our efforts to make the shift from curative to preventive care. We are looking at how we can make and keep horses healthy through nutrition."

Simulating digestion

Laminitis is a serious condition and is caused by a painful inflammatory reaction in the horse's hoof. "There are multiple conditions that can lead to laminitis but from a nutritional perspective, grass sugars and starch are the culprits," says Hendriks. "Our platform allows us to study the consequences for a horse's enterohepatic system."

In order to do so non-invasively, the researchers are adapting a process to simulate digestion that has already been used for other animals. The team is particularly interested in the part that remains undigested and is fermented in the colon. Hendriks: "To study fermentation, we use the 'in vitro gas production technique' (IVGPT). So no live animals are needed for this study." The researchers work with material from horse manure or the intestinal contents of cadavers. "We then introduce the portion that is undigested into the IVGPT to further investigate the fermentation process in the caecum and colon."

Research with mini-organs.

"We are also interested in the metabolites that gut bacteria produce," Hendriks says. "You can think of those as the weapons that bacteria use in a kind of chemical warfare. One bacterium produces a molecule that another bacterium cannot process, which is a metabolite. What we want to know is: what metabolites are produced when a horse eats a lot of grain, for example, or a lot of grass? And how do those affect the enterohepatic system?"

To investigate the effects of those substances, the scientists use organoids. These are a kind of miniature organs made by growing stem cells from horses into intestinal or liver cells. "With organoids, we can mimic the impact of disturbed intestinal flora on these organs and see how the liver metabolizes these harmful substances," he said. The expectation is that, under certain conditions, substances that cause inflammatory responses will be produced."

Animal-free digestive research

"Our research provides a collection of clearly controlled experiments that will allow researchers around the world to simulate equine digestion. Moreover, future researchers can build on our platform to mimic even more processes in the equine body," Hendriks said. A paradigm shift is needed in the field of internal animal research, NWO's National Science Agenda states. "This project contributes to that switch to research that does not require live horses."

The research is primarily important for the horse industry - think producers of horse feeds, for example. In the Netherlands, more than one and a half billion euros is spent annually in the horse sector. "In addition, the platform will also be important for research on animals with similar digestive systems, such as donkeys, for example, and even research on cattle will benefit," Hendriks explains.

Collaboration partners

Within NWO's Open Technology Program, 4.3 million is available for research with a societal application. Industry adds almost 400,000 euros to that. Bacin2DLiver is a collaboration between Wageningen University & Research and Utrecht University, two universities that conduct a lot of equine research. It is also supported by Cavalor, PAVO, and Mad Barn and the Horse Sector Council (“Sectorraad Paarden”) of the Netherlands.