New research focuses on preventing GI disease before it happens

Gastrointestinal (GI) issues like vomiting and diarrhea are one of the most common health issues veterinarians treat in dogs. Now, researchers are working to find ways to identify dogs that may be predisposed to gastrointestinal disease—even before they show outward symptoms of GI distress.

The end goal: finding interventions that can prevent or lessen GI disease impact, and to help commonly-affected breeds live longer, healthier lives.

The research

In a study published in February in the Journal of Veterinary Internal Medicine, a team of researchers from Texas A&M’s Gastrointestinal Laboratory outlined their discovery of various “biomarkers,” or biological indicators, that can be used to predict likely future canine GI disease onset.

The study, led by associate professor, small animal internist, and board-certified veterinary nutritionist M. Katherine “Katie” Tolbert, DVM, PhD, DACVIM-SAIM, focused on soft coated Wheaten terriers. The breed is known to be predisposed to protein-losing enteropathy (PLE). Canine PLE, also common in breeds like the Yorkshire terrier and German shepherd, is a severe digestive condition marked by excessive protein “leaks” into the GI tract, resulting in recurrent diarrhea, vomiting, lethargy, muscle waste, and potential death.

“The research emerged from collaborative work I was doing with TriviumVet, an Irish company,” Tolbert explained. “Our goal was to develop an early diagnostic that could be used to identify dogs that had gastrointestinal disease before any clinical signs emerged.”

Biomarkers as disease indicators

Working in cooperation with the Soft Coated Wheaten Terrier Club of America, Tolbert’s team compared biomarkers of Wheaten terriers who had previously been clinically diagnosed with PLE to Wheatens who had not yet shown clinical PLE signs. A third group, composed of other breeds not prone to developing PLE, served as the control.

The study identified several biomarkers that could indicate a high risk for GI disease, including inflammation, changes to gut microbial composition and so-called “leaky” gut, or increased intestinal permeability. These canine biomarkers mirror clinical biomarkers already used to identify preclinical inflammatory bowel disease (IBD) in humans.

As part of the research, Tolbert’s team had participating dogs swallow video endoscope capsules, or “PillCams,” to enable video observation of their GI tracts.

“We’re looking for new things that might be able to be identified before [traditional] lab work abnormalities appear,” Tolbert said.

Tolbert’s findings in the study showed that, in terms of some of GI biomarkers, the “healthy” soft coated Wheaten terriers more closely resembled dogs with full-blown, diagnosed PLE than they did truly healthy dogs. These results suggest there may be a subclinical period where evidence of GI disease begins, even before the dogs get sick enough that their owners notice something is wrong.

Still, it’s important to note that although being a Wheaten is a risk factor, that’s generally not enough to cause disease; other factors like early life infection, a history of antibiotics, or malnutrition could also be factors.

What follows these findings

Next, Tolbert’s team plans to explore whether or not introducing specific dietary interventions could help lessen the severity of—or even prevent—PLE in dogs at high risk of developing the condition.

“Canine patients with severe types of chronic GI disease often end up having really negative outcomes, so these conditions are really hard on the dogs and really hard on the owners,” said Kylie Grady, DVM, a PhD student on Tolbert’s team who is helping lead the second phase of research.  “Our goal is to catch these dogs before they get in those awful clinical spots and see if targeted diets could be used to change some of these underlying markers and potentially help prevent GI disease development.”

Through collaboration with a leading dog food manufacturer, Tolbert’s research team plans to test three existing prescription diets to see if they might serve as an effective dietary intervention for dogs predisposed to GI disease.

The role of diet

Research suggests that canine PLE may stem in part from a dog’s immune system reacting abnormally to the beef or chicken protein that’s in their diet. So, dietary intervention typically includes introducing either a new protein source—like salmon or soy—or adding a hydrolyzed diet, in which beef or chicken protein sources are broken down into such small molecules that the immune system doesn’t recognize them.

The new study will explore if introducing a hydrolyzed or novel protein, low-fat diet prior to PLE symptom onset reduces the rate of eventual symptom development in dogs prone to the condition, compared to dogs in a control group who will be fed a standard diet. The planned research will again involve Wheatens, with a future goal to explore dietary interventions for other PLE-prone breeds.

“My guess is what works for the Wheaton may not work for the Yorkie or the German shepherd, but we can later use the same principles and the same kind of study design to figure out what will be the best dietary intervention for each type of breed,” Tolbert said.

Rethinking best practices

The planned next-round study will be performed at Texas & AM in partnership with teams at North Carolina State University and Michigan State University, where assistant professor Sara Jablonski, DVM, PhD, DACVIM-SAIM, has made researching a solution to canine PLE her career mission.

Jablonski’s focus on PLE emerged from her treatment of a young Samoyed named Libby during the first year of her internal medicine residency. Libby had not been responding to typical treatment protocols, which called for use of immunosuppressive medications.

“She was just not getting better with anything we tried,” Jablonski said. “We ended up switching her to a homemade diet that I’d seen described in someone’s conference proceedings, and she started doing much better. We were eventually able to get her back to normal—and I came away fascinated that what she responded to was sort of in conflict with everything I had learned [in veterinary school].”

Now, 90% of Jablonski’s research at Michigan State centers on ways to shift the odds in favor of longer, healthier lives for dogs with PLE.

Based on her research findings, Jablonski now prefers to treat her canine PLE patients by prioritizing dietary intervention, with a reduced focus on aggressive immunosuppression.

“I’ve seen dogs [with severe cases of PLE] that used to go on to get euthanized actually be able to turn around and start responding to dietary intervention and then do quite well for the long term,” Jablonski said.

A PLE partnership

Their shared interest in reframing PLE treatment best practices has forged not only a close research collaboration between Tolbert and Jablonski, but a true friendship. Together, they hope their work can help advance new standards of care for dogs with severe GI conditions.

“Historically, what we learned in school is that 50% of dogs with PLE will die from it,” Jablonski said. “And I couldn’t think of a better thing to focus on than trying to make those outcomes better.”

Tolbert agreed. “Our clinical studies have illustrated that if you lead with diet, these dogs have a much better chance at survival. I think our work is changing some of the narrative around PLE. With my own clinical cases, I would now say that for dogs where we’re actively targeting and tailoring their diets, roughly 80% to 90% are living full lives.”

Duncan, a soft coated Wheaten terrier in Waterford, Michigan, is one of those success stories. Now 11, Duncan has been seeing Jablonski for treatment and following a modified diet since he developed severe diarrhea and was diagnosed with PLE two years ago.

“We ended up trying probably three or four different types of food, including canned food, and then kibble, then hydrolyzed kibble,” said Duncan’s owner, Lorie Dietz. “We’ve settled on a diet of home-cooked tilapia combined with a prescription dog food made from white fish and potatoes.”

Now that Duncan’s best-fit dietary intervention is in place, his GI symptoms have been well controlled with only a small dose of prednisone every other day.

“It’s working great,” Dietz said. “He’s happy and playful like our two other soft coated Wheatens, and these days you would never even know he has a problem.”

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