Anorexia is normally treated with therapy. Now a Canadian team is trying the gut

Anorexia is a life-threatening eating disorder that can manifest as an intense preoccupation on weight loss.

It's classified as a mental illness and normally treated with talk therapy, known as family-based therapy, but that's only effective for about half of the mostly women and girls who have it.

Those who don't improve may go to hospital and get locked into a relentless cycle of gaining weight and recovering from malnourishment, followed by weight loss and damage to organs, including changes to the brain from starvation.

Now, Canadian researchers are testing a new approach, tapping into the growing understanding of the gut-brain connection.

They're going to try treating teens with fecal transplants, to change the bacteria in their gut.

"We know that once the symptoms set in and the brain changes, it's really hard to change the course, so if we can intervene early in the adolescent years, we have the best chance," said Dr. Jennifer Couturier, a child psychiatrist and associate professor of psychiatry at McMaster University in Hamilton, Ont.

In fecal microbial transplants, a small sample of stool from a healthy person is purified to concentrate the beneficial bacteria minus the waste. The microbiome is then put in a capsule, which the recipient takes for therapeutic purposes.

Couturier and her team have Health Canada approval to run a randomized clinical trial in an initial group of 20 females aged 12 to 17 diagnosed with anorexia. They will either take oral capsules along with standard family-based treatment to stabilize nutrition and avoid the harmful effects of starvation or family-based treatment alone.

Fecal transplants have been tested in a small handful of adults with anorexia, including one who restored her weight.

In this trial, the McMaster researchers will use the university's own stool bank of donations.

Dr. Nikhil Pai, a gastroenterologist at McMaster and a co-investigator on the trial, credited the university's contributions for funding the research and starting the pediatric stool bank.

"This is not affiliated with any company," Pai said. "We developed this entirely in-house using carefully screened pediatric donors."

Pai said the screening checks for infectious diseases, similar to how blood donations are assessed. Staff at the stool bank then prepare the capsules, which can't be mass produced.

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There are a few reasons Pai and some other doctors are optimistic participants will benefit.

One comes from animal studies. Researchers transplanted gut microbes from humans with anorexia to normal mice models, and found the mice reduced their food intake as if anorexic. Then, when gut microbes from healthy humans were given, the effect reversed.

Secondly, young guts are subject to change. Pai said the gut microbiome is malleable in children and teens.

"It actually is a very different landscape in adolescence, where if you can make a change, you not only may see some improvement in terms of outcomes for anorexia nervosa in the short term, but … the sustained response," Pai said.

With every meal, trillions of gut bacteria turn breakfast, lunch and dinner into molecules called metabolites that affect the brain.

Pai, who also works at Children's Hospital of Philadelphia, said large population-based studies show a few types of bacteria can have an outsized effect on the brain through the gut-brain axis, a connection between the two.

"When we feel a bit nervous, sometimes we feel butterflies in our stomach," as a symptom of the nervousness, Pai said.

"It's no surprise that we often have these intestinal symptoms that come along with the psychological anxieties."

Researchers will follow participants in the clinical trial for eight weeks while they receive the capsules and then for four weeks after that. Pai and Couturier say one aspect they'll record is whether participants are willing to take the fecal transplant — or repulsed by it.

Then they'll measure how the patient is doing — by tracking their weight, and mood — and how the microbiome changes based on saliva, urine and stool samples.

Scientists are learning more about how gut microbes influence brain function.

Various studies have shown people with some psychological problems, including anorexia nervosa, having abnormal intestinal microbes, said Dr. Howard Steiger, former director of McGill's eating disorder program.

"We always like to think of the brain as being the command centre for the body," Steiger said. "But you know, a lot of recent findings suggest the gut also controls your brain."

In people with anorexia, Steiger said, the thought is that their eating behaviour messes up the way gut microbes influence functions in the brain and body.

Given that, transplanting purified fecal samples from healthy individuals could help those with anorexia, said the professor emeritus of psychiatry, who continues to treat people with eating disorders

"It's not like total voodoo to think that [fecal transplant] would be a potential adjunct in treatment or maybe even a treatment in itself," Steiger said.

Some clinicians now refer to anorexia as a "metabo-psychiatric problem," meaning it is associated with vulnerability both in the brain and the body.

"I think that's important because it reduces shame," Steiger said. "People don't develop anorexia because of moral weakness. They carry a real, physical, heritable susceptibility." That means anorexia gets triggered by a combination of nature, or genetics, and nurture, such as life events.

Anita Federici, a clinical psychologist north of Toronto, treats adolescents with anorexia using family-based therapy.

Federici said initially, the parents or caregivers are empowered to learn how to nourish their child by taking over all meal and snack preparation and supervising intake and weight checks.

Then the child might start eating lunch at school unsupervised. In the last phase, the youth regains independence over eating and exercise.

About half of younger people with anorexia nervosa who receive family-based treatment for it do really well, Federici said.

But anorexia rarely "flies solo," Federici said, noting many people also have co-occurring suicidal thoughts or experience self injury, substance use, trauma or PTSD, as well as neurodiversity like autism. All can complicate the picture.

Federici said the standard approach of medicalizing treatment for anorexia focuses on gaining weight. Treatment that doesn't take into account the metabolic underpinnings of anorexia can miss the mark, Federici says.

"There was research not long ago that demonstrated that there were more serotonin receptors in your gut than there were in your brain," she said, referring to a neurotransmitter with roles including influencing mood.

"So it begs the question, you know, can you influence the gut itself to impact something like an eating disorder?"

Taking the metabolic basis of anorexia into consideration could mean clinicians may need to change how they feed patients, both in terms of the types of food and the pacing of meals, Federici said.

In people with anorexia, the body is dysregulated so they feel soothed when they eat less. While bystanders may think the patient isn't motivated to change, Federici said in reality they're quite motivated.

"What I have observed over the years is that these people desperately want to get better. They desperately want a different life, but they need the treatments to be different."