WCVM researchers use metabolomics to explore avian influenza questions

Metabolomics is the study of the small molecules used or produced by the body during metabolic processes such as converting energy in food to energy available for cellular activity. Metabolomics promises to answer key questions about AIV as well as stress and its effect on animal systems — a longstanding research focus for Dr. Karen Machin, the study’s lead investigator.

“The more I do metabolomics, the more interested and excited I get,” says Machin, an associate professor in the WCVM’s Department of Veterinary Biomedical Sciences. “I’m very mechanistic, I guess. I like to know why and how things happen.”

AIV is a type of influenza virus that occurs naturally among waterfowl and can infect domestic poultry and people. Although waterfowl don’t usually get sick from an AIV infection, they’re great carriers of the disease and can transmit it to other species that do get sick and can die from it.

As human development encroaches upon and destroys more waterfowl habitat each year, waterfowl live in closer proximity with people, and the risk of AIV infection in the human population is increasing.

In addition, habitat destruction and climate change are stressors for waterfowl, and those higher stress levels lead to higher susceptibility to AIV.  

Although the most common strains of AIV are considered “low pathogenic” (causing mild disease), wildlife scientists are growing more concerned about the virus’s potential to mutate and become highly pathogenic — causing more sickness and death in waterfowl, domestic bird species and people alike.

While researchers know that AIV primarily affects the host’s respiratory and gastrointestinal systems, they want to understand its impact on the whole body — and that’s information they can access using metabolomics.

Once they can recognize how AIV affects metabolic pathways, they can use that knowledge to diagnose AIV sooner and determine targets for treatment.

“You’re trying to figure out if you’re positive for a low pathogenic avian influenza, what does your metabolome (total number of metabolites present within an organism) look like? Can I tell the difference between individuals that have it [AIV] and don’t have it based on their metabolomes?” asks Machin.

She’s also interested in determining whether these metabolic indicators can be tied into physiological changes such as corticosterone levels in wild birds’ feathers.

Corticosterone, the main hormone produced by birds in response to stress, suppresses the immune system and increases blood sugar by increasing metabolism. In mammals the cortisol hormone has very similar functions.

“We think of stress as always being bad, but it’s not always bad,” says Machin. “Cortisol rises in mammals because of excitement, because they’re happy, and during normal bodily processes, so it’s really hard to just measure stress.”

Similarly, measurements of corticosterone are used to evaluate the level of stress experienced by an animal, but those measurements don’t tell the whole story. Researchers need more information to fully understand stress — information that can be gleaned from metabolomics. 

Although metabolomics may be a lower-cost alternative to measuring corticosterone, scientists need to do more research. They must establish how much information metabolomics can provide and determine whether it can replace corticosterone measurements — or if it needs to be used in conjunction with them.

In addition to her AIV research work and other responsibilities as a WCVM faculty member, Machin is completing a residency in clinical animal behaviour. From that perspective, Machin hopes to use metabolomics to learn more about how therapeutic drugs work and to develop personalized medicine for dogs, cats and other animals with behavioural issues.

Ideally, she would like to use metabolomics in her clinical practice by coupling it with behaviour therapies to evaluate a patient’s response to therapeutic treatments earlier.

“We can’t know for sure if we use a drug, that it is going to work. It’s a guess based on history, behaviour and interpretation,” says Machin. She adds that it often takes four to six weeks of dosage before owners notice any behavioural changes in their pets.

“But maybe there are physiological changes we can see earlier that tell us if a drug is working or not, and we can switch them to a different drug, so you don’t have to wait and be frustrated. There are so many applications as I see it.”

Metabolomics can also provide information about the underlying mechanisms of drug metabolism. Once more is known about the effects of stress and disease in animals, that information can be used to develop personalized medicine protocols for use in veterinary patients.

“People are using [metabolomics] more and more to get at what’s going on inside the individual, and metabolomics is becoming really exciting in terms of human medicine with a targeted approach,” says Machin.

“The hope is … that we will utilize that [data] to determine if our therapies are working or not, and veterinary medicine hasn’t even talked about that, so we’re just learning of ways to apply this.”

Paige Hinton of Winnipeg, Man., is a fourth-year veterinary student at the Western College of Veterinary Medicine (WCVM) who worked as a summer research student in 2021. Her story is part of a series of articles written by WCVM summer research students.