Mar 5th 2026|5 min read
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FIFTEEN YEARS ago Valerie Taylor, a psychiatrist at the University of Calgary, in Canada, was approached by two people with bipolar disorder, a severe mental illness involving manic and depressive phases. Neither of them had received any benefit from standard treatments, but their symptoms had markedly improved after taking antibiotics. They were keen to know: was there a link?
Dr Taylor has spent the intervening years trying to find out. The results of her latest study, published on March 5th in the Canadian Journal of Psychiatry, provide hints that a link between the composition of bacteria in a person’s gut—known as the gut microbiome—and bipolar symptoms, may indeed exist. If so, further work could one day lead to new ways to treat the disorder, using interventions that target the microbiome. As there are few effective treatments for bipolar disorder, this would be a boon for the estimated 37m people who have the condition worldwide.
The idea that gut microbes can influence the brain is no longer controversial. Over the past 15 years studies have shown that the gut and the brain probably communicate via four main routes. The most direct is via the vagus nerve, which connects the enteric nervous system (a web of neurons lining the gut, sometimes called the “second brain”) to the brain. Gut microbes also influence a network of brain regions and glands known as the hypothalamic-pituitary-adrenal (HPA) axis, which controls stress responses, primarily by releasing cortisol, a hormone. The microbiome also interacts with the immune system in various ways. Finally, by-products of bacterial metabolism, such as short-chain fatty acids (SCFAs), can enter the bloodstream and from there cross into the brain. Collectively, researchers call these links the “gut-brain axis”.
Two studies published in 2016 showed that transferring the gut microbiome of depressed humans to rodents gave the animals depression-like symptoms. That got Dr Taylor wondering if the reverse was also possible: transplanting a healthy microbiome to treat mental illness.
To find out, Dr Taylor and colleagues conducted a pilot trial in 35 patients with depressive-phase bipolar disorder. It was a double-blind randomised controlled trial, one in which neither participants nor researchers know who gets the treatment being studied and who gets an ineffective control. The researchers used a procedure known as a faecal microbiota transplant (FMT), which involves transplanting stool from a healthy donor with the aim of resetting the microbiome. For this trial, so-called autologous FMT (prepared from the patient’s own stool) was used for the control whereas “allogenic” FMT (from a healthy donor) was used as the treatment.
Almost every participant in the trial saw their symptoms improve when assessed six months later. As there was no significant difference between the treatment and control groups—participants who received autologous FMT also got better—it is possible that all the improvements were due to the placebo effect. “It’s a well-designed experiment, and the effect sizes look good, but it’s hard to judge without a proper placebo,” says John Cryan, a professor of anatomy at University College Cork in Ireland, who wrote a commentary published alongside the study.
All the same, the results of Dr Taylor’s trial will facilitate future experiments. An important goal of her study was to show that FMT for bipolar disorder is safe and tolerable for patients. None of the participants in Dr Taylor’s trial had any adverse effects, which will be encouraging for those looking to run larger studies.
There is an obvious place for such studies to start. Dr Taylor is of the opinion that autologous FMT may be much more than an inert placebo. Collecting, processing, and reinfusing a patient’s own stool, together with a preceding bowel cleanse, also alters the microbiome, and Dr Taylor believes this influenced symptoms. It is a plausible hypothesis. “If you dig up your garden and put it back down again, your garden benefits,” says Dr Cryan. “It’s ploughing as opposed to resodding.”
Other research appears to back it up. A trial published in 2019 in people with irritable bowel syndrome (IBS) found no significant difference between allogenic and autologous transplants up to six months later. Another, in individuals with Parkinson’s disease, published in 2024, also found no difference at six months, but after 12 months participants who received allogenic transplants did significantly better. This suggests that any benefits of autologous transplants may be temporary.
Dr Taylor and her team are now using true placebos to investigate other conditions. Two ongoing trials are for depression, one is for obsessive-compulsive disorder and another is in the works for attention deficit hyperactivity disorder.
During the bipolar-disorder trial, Dr Taylor’s team sought to identify which bacterial species changed most in patients who benefited. She hopes that one day it will be possible to turn these beneficial bacteria into a medication known as a probiotic. Faecal transplants could then be replaced by more conventional, oral treatments which would be easier to deliver and potentially more palatable to patients. To this end, Dr Taylor has set up a spin-out company, Taylored Biotherapeutics.
Understanding the exact mechanism whereby such interventions work remains a challenge. To address this, Dr Taylor’s team plan to test their new probiotic in a future trial for bipolar disorder, which will look not only at changes in bacterial species, but at the effects those changes have on various biological functions.
The two most likely pathways are SCFA production and inflammation, says Jane Foster, a neuroscientist at the University of Texas Southwestern Medical Centre, who was not involved in the study. SCFAs, such as butyrate, are the main fuel for cells that line the colon, and help maintain the gut barrier. They also influence immune function and reduce inflammation, heightened levels of which have long been linked to depression. “When you have changes in your gut microbiome with bipolar disorder or depression, you also have increased inflammation and reduced production of SCFAs,” says Dr Foster. “These are the low-hanging fruit to investigate further.”
The key to exploiting the microbiome for mental health will be understanding which pathways are important in which individuals, says Dr Foster. To do that, bigger trials—armed with true placebos—will be needed to scrutinise differences between patients who do and don’t respond. ■
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This article appeared in the Science & technology section of the print edition under the headline “Gut feelings”
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