Human medicine to help get to the guts of equine disease

The in vitro "Robogut" at the University of Guelph.
The in vitro “Robogut” at the University of Guelph.

Advances in human gut health could pave the way to greater understanding of equine gut bacteria and its relationship to horse diseases, thanks to a new collaboration between two Canadian researchers.

Links between the gut microbiome and human health have gained much attention in the past few years. Changes in the human microbiome have been linked to obesity, diabetes and more. These findings spurred researchers to investigate the microbiome in horses, and many now believe that the microbiota are key to understanding horse health and diseases, such as colic.

At the University of Guelph Dr Luis Arroyo, a researcher and clinician focused on large animal health, has teamed up with Dr Emma Allen-Vercoe, whose main focus is on links between the gut microbiome and health in humans.

They hope to use an in vitro system known as Robogut, developed by Allen-Vercoe, to answer questions about the gut bacteria in healthy horses and those affected with disease, such as colitis. Robogut, a combination of beakers, tubes and monitors, simulates the human gut and allows researchers to explore the human microbiome. For instance, Robogut has been used to investigate the impact that high protein diets have on the microbiome when compared to high fibre diets.

Both researchers emphasize key differences between horses and humans that will need to be accounted for when transitioning Robogut from a simulated human gut to a horse gut. For one, horses generally have a more standardized diet than humans. Many humans eat vastly different meals each day. Different nutrients have different and often rapid impacts on the microbiome. Setting up Robogut for horses may be more straightforward in this respect, as the researchers will not have to account for such a large amount of variation. However, the unique characteristics of the equine digestive system may also make setting up Robogut more complicated.

Prof. Emma Allen-Vercoe at work in what she fondly calls her “poopy” lab in the science complex. 
Prof. Emma Allen-Vercoe at work in what she fondly calls her “poopy” lab in the science complex. © Martin Schwalbe

“Horses are hindgut fermenters, and rely on the bacteria in their cecum and colon to produce as much as 70% of their energy needs” says Arroyo.

Since the intestinal tract of the horse is much different from humans, researchers first need to understand what conditions are necessary for microbial growth in horses, to ensure that Robogut’s experimental set up accurately reflects that environment. Arroyo is overseeing the research that will answer these questions.

First, fecal samples were collected from healthy horses and horses with colitis. DNA sequencing was completed on the samples to determine and compare the microbes present in the intestinal tracts of these horses. Researchers also grew the samples under different experimental conditions, to understand how these conditions would affect the growth of different microbial species. The samples were grown using close to 50 different media types (this changes the nutrients that the bacteria feed on), and under aerobic and anaerobic conditions. Researchers then harvested the samples, and are currently completing DNA sequencing. From these experiments, comparisons can be made between the original samples collected from the horses, and those grown by the researchers, to determine which conditions resulted in optimal microbial growth. These comparisons will help Arroyo and Allen-Vercoe determine the right experimental conditions to use for Robogut to mimic a horse gut.

Although the differences between horses and humans can make experimental set up more time-consuming, studies in humans can often help researchers identify new areas of investigation in horses.

Dr Luis Arroyo
Dr Luis Arroyo

For example, scientists now believe that many cases of colitis in humans are due to imbalances in the microbiome, and not pathogens as was previously thought. These findings guided the research into microbiome and colitis in horses, including this project. Dietary change has also been linked to effects on the microbiome in humans. Allen-Vercoe cites a study performed in her lab where a switch from a high protein diet to a high fibre diet did not affect the composition of the microbiome, but resulted in rapid changes to the abundance profile. This area is now being investigated in horses as well. Instances of antibiotic use, stress and bottle feeding with milk substitutes can also be found in both species. These have all been associated with effects on the microbiome in humans and are now areas of interest in horses as well.

Allen-Vercoe adds weaning as a topic of interest, stating that “weaning can cause a lot of stress to the foal, especially if it is done too early or is forced. This stress combined with change to the diet can have a rapid and huge impact on the microbiome, and may be a cause of diarrhea seen in foals.” Allen-Vercoe believes weaning should always be done very slowly in all species to prevent these negative effects.

Arroyo is excited to get back the results of the initial experiments. He says “these results will help us understand what a healthy horse microbiome looks like, and will make sure that our experiments with Robogut will be of the utmost value.”

The research is supported by funding from Equine Guelph, Emerging Leaders of Latin America and The Natural Sciences and Engineering Research Council of Canada (NSERC).

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