2024-03-03 13:07:35
The Wageningen Animal Sciences Research Unit and the Utrecht Faculty of Veterinary Medicine hope to uncover what exactly triggers laminitis from the gastrointestinal tract, a painful inflammatory reaction that causes many horses and ponies to be euthanized.
A lot can go wrong in a horse’s belly. Serious conditions such as colic (collective name for abdominal pain in horses) and various forms of laminitis (also known as laminitis, see box) originate in this part of the body. But it is very difficult to determine what exactly goes wrong. This is partly due to the anatomy: with approximately 20 meters of small intestine, about 9 meters of large intestine and an appendix capacity of approximately 35 liters, it is difficult to put the proverbial finger on exactly the sore spot. Post-mortem examination also only provides partial guidance. ‘In these conditions, the kinetics, the speed at which nutrients are absorbed or broken down, is a crucial factor. Certain chain reactions occur that can no longer be properly analyzed after death has occurred,’ explains Wouter Hendriks, professor of Animal Nutrition at both WUR and UU.
He leads the joint research project on equine digestion, called Bacin2Liver. Bacin2Liver does not seek refuge in the horse’s body, but in the lab: it develops a platform that simulates horse-specific digestion; both digestion in the small intestine and fermentation in the large intestine and cecum. Hendriks: ‘We look at the kinetics that take place, plus which metabolites the intestinal bacteria produce and how they influence intestinal and liver function. We do this with organoids, stem cells from horses that we have grown into intestinal or liver cell systems. We investigate how they react when metabolism changes and toxins are formed as a result. So we are going to generate a tremendous amount of knowledge about detailed processes in digestion.’ The method used, the ‘in vitro gas production technique’ (IVGPT), is already used for digestive research in pigs, dogs and cats.
Sugar metabolism
In equines it is known that fructans and starch can play a questionable role in digestion; that they sometimes disrupt the fermentation process in the large intestine. It is also established that certain horse and pony breeds are more susceptible to laminitis than others – and those breeds are also more susceptible to diabetes. Hendriks: ‘We already know from previous research that things are going wrong in sugar metabolism.
This project contributes to a future free of animal testing
But what exactly triggers the inflammatory response of laminitis is still a black box. The organoids must tell us what exactly happens with that sugar metabolism. “With our platform we will soon be able to accurately investigate how quickly or slowly certain substances are broken down, how well or poorly digestion proceeds and how they influence fermentation – all of which could be indications of exactly how laminitis develops,” he explains.
Together with the Wageningen-Utrecht research team, Hendriks expects to be able to reveal under what conditions which substances are formed in the intestine that cause the inflammatory response of laminitis. ‘We already have ideas about this: there is an overgrowth of certain micro-organisms that produce specific toxins when the pH value drops due to fermentation in the large intestine. The key question is: which toxins are those? If we can unravel this through the organoids, and what the conditions are under which it occurs, then we should also be able to determine how this can be prevented.’
Public platform
In addition to solving the laminitis puzzle, the Wageningen-Utrecht project also aims to create a platform on which researchers can eventually build further, in order to be able to imitate even more processes in the horse’s body, says Hendriks. ‘This project contributes to a future free of animal testing.’ There is no clearly demarcated division of tasks, he says.
Projects with horses are always very popular
‘The organoids are somewhat more the domain of Utrecht. WUR can also make them, but Utrecht has more experience with specific horse organoids. And in vitro digestion is a little more on the Wageningen path. But we don’t want competition; both universities do what is necessary to create this platform.’ There is also no question of secrecy towards the outside world. ‘We make everything public, including the specifications of the organoids and the conditions of the tests. So that other researchers also benefit from our acquired knowledge and insights.’
The four-year project will receive half a million euros from science financier NWO. In addition, the Horse Sector Council and a number of feed producers contribute financially, for a total of 100 thousand euros. The project budget will cover at least one PhD position. Hendriks also hopes to attract a fellow, a PhD candidate with a grant. He expects there is also a lot in store for students. ‘Research projects with horses and companion animals are always very popular. These are normally relatively rare in Wageningen, but this project offers ample opportunities for research projects for master’s students.’
Hoof problem
Laminitis is also called laminitis. It is an inflammatory response that affects the connection between the hoof wall and the internal hoof structure. It consists of lamellae, which hold the hoof wall and the internal hoof structure together like a kind of Velcro. In severe cases, that connection loosens. This can cause a small bone inside the hoof (the hoof bone) to tilt, which in extreme cases even perforates the sole of the hoof. The animal can then usually no longer be saved. Even in less severe cases, laminitis is very painful; horses can barely walk and adopt a typical posture.
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