By Erin Howe
Illustration by Jud Haynes
“No one with depression would volunteer for a colonoscopy they don’t need.”
Valerie Taylor remembers a colleague expressing their skepticism nearly a decade ago when she began to wonder whether fecal microbiota transplants (FMTs) could help people with treatment-resistant bipolar depression (BPD). But once Taylor began to recruit participants to take part in her research, looking at how an FMT might benefit their mental health issues, she was astonished by the patients’ interest.
“The concept of a link between a patient’s gastrointestinal [GI] system and their anxiety or depression symptoms is something that many people who have psychiatric illnesses have been trying to get somebody to take seriously for years,” says Taylor, who has been a professor of psychiatry at the University of Calgary’s Cumming School of Medicine since 2018.
Previously, Taylor worked at the University of Toronto, which is where she cultivated the idea of doing research in this area, as part of the Microbiota Therapeutics Outcome Program (MTOP), a collaborative multidisciplinary program supported by U of T, University Health Network and Sinai Health System.
The theory was that gut bacteria from stool donors without mental health conditions would be placed into the digestive systems of people with treatment-resistant BPD through colonoscopies — in the hopes it might improve BPD symptoms. Patients responded enthusiastically, she says. Some patients told Taylor that when their depression got worse, their GI system acted up. Others told her that they could predict a depressive episode coming on because they had digestive symptoms before mood symptoms began.
“Patients had been told for a long time that it was all in their heads. But, I thought it was also in their GI systems. And, my work seeks to show how those two things are connected,” says Taylor, the psychiatry lead and a co-investigator at MTOP.
The second brain
Taylor’s work is just one type of research looking at how the mind is connected to the digestive system. It’s common to hear the gut referred to as the body’s second brain, thanks to the enteric nervous system, a collection of more than 100 million neurons that stretch from the esophagus to the rectum. Here, trillions of micro-organisms help digest food, provide protection from inflammation and infection, and even influence mood and energy levels.
Research has shown that people with inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis, which can cause severe diarrhea and stomach cramps, have a higher risk of experiencing depression or anxiety.
However, the link doesn’t exist in all conditions. For example, it hasn’t been established in deeply painful conditions like bone cancer, explains Taylor. Since 2020, she has been collecting blood, stool, urine and saliva samples from volunteers and following up with them regularly to examine the microbiome at various points in time and in varying degrees of health, as part of North America’s largest biological neuroscience microbiome bank.
“There seems to be a specific relationship between GI illness and increased risks of depression and anxiety,” she says. Researchers such as Taylor are still trying to better understand what role the gut-brain plays in conditions like bipolar disorder, depression and schizophrenia.
Do biomarkers hold the key?
According to the Canadian Institute for Health Information, in any given year, about one in five Canadians experiences mental health or substance use issues. About a third will experience mental illness in their lifetime. Before she began her medical training, psychiatry resident Kenya Costa-Dookhan (MSc ’20, MD ’24) was curious about the brain-body connection in mental health.
As a master’s student, Costa-Dookhan explored the gut microbiome in people who experience their first episode of psychosis in conditions like schizophrenia. She also wanted to see what happens in the gut when people begin to take antipsychotic medications. Through her research, Costa-Dookhan saw that even in a small sample size, there were differences in the gut microbiome between people first diagnosed with schizophrenia spectrum disorders and the healthy control group.
“These patterns in the microbiome also appeared to change after treatment with antipsychotics began,” says Costa-Dookhan.
People with schizophrenia spectrum disorders are up to five times more likely to develop type 2 diabetes than people without the disorder. The risk of death from cardiovascular disease is also double that of the general population. A known side-effect of second-generation antipsychotic medications, which are commonly used to help treat schizophrenia spectrum disorders, is weight gain. And a growing body of evidence also suggests that the gut microbiome may play a part in metabolic dysfunction.
“The more we uncover about these potential biomarkers, the more we realize how much there still is to learn,” says Costa-Dookhan. “And because there are limits to what our current medication can do, finding another avenue for treatment through the gut microbiome could be helpful.”
The role of age
In addition to looking at the gut’s impact across a range of mental health conditions, researchers are also working to better understand the role the gut plays in emotional well-being at various stages across the lifespan.
Susan Campisi (MHSc ’94, PhD ’20) is a research associate in the lab of Professor Daphne Korczak (PGME ’06) at The Hospital for Sick Children (SickKids) whose research focuses on paediatric nutritional psychiatry. For some illnesses, such as diabetes or cardiovascular disease, there’s been a long-standing appreciation of the association between food and its effects on physical health.
But the appetite for research into the ways diet can affect mood has only begun to grow over the last couple of decades, says Campisi, who is also an adjunct lecturer at the Dalla Lana School of Public Health’s Nutrition and Dietetics Program at U of T.
“The number of publications has skyrocketed since 2010, but the explosion of nutritional psychiatry research was really among adults. When we compare the volume of research to that done with child and adolescent groups, there’s a huge disparity,” she says. “These are critical times for development. If we can intervene early, maybe there’s potential for longer-lasting effects.” In the Korczak Lab, Campisi looks at diet in teens with depression.
The team has done systematic reviews of existing gut microbiome studies and looked at clinical populations of kids and teens who participate in the Children’s Integrated Mood and Body Program (better known as the CLIMB Program) to learn about the relationship of diet in kids with and without depression. They found that youth with depression have similar eating habits to their peers, including their intake of so-called “junk food.”
They also noticed the patterns diverged when it came to the quantity of fruits and vegetables. The teenagers with depression ate fewer fruits and vegetables. To find out when that change begins to set in, Campisi and her colleagues looked at data from the CHILD Cohort Study. It began in 2009 and followed expectant parents from mid-pregnancy through to their child’s adolescent years.
“We saw that the signal existed even at the preschool age, which was interesting to see. And there’s still plenty more to explore,” she says.
What’s on the horizon
For overall gut health, a wealth of evidence points to the benefits of a whole-food diet rich in fruits, vegetables, legumes, fermented foods like kefir, kimchi and kombucha, and low in highly processed foods. But so far, there isn’t science to support recommendations for any particular diet or specific strains of prebiotics or probiotics for adolescents with depression.
Yet, one day that could change.
Taylor and her team continue to explore how changing a person’s gut bacteria through fecal material transplant can affect conditions such as depression and obsessive-compulsive disorder, and whether they can identify the specific bacteria involved to design new therapies. The group has also developed their first precision probiotic to help relieve bipolar depression symptoms. They hope to begin clinical trials by the end of 2026.
“The field is changing every day. The research has led to the creation of new treatments, which we hope will help make people better,” says Taylor.