Scientists know our gut influences our brain. So psychobiotic drugs that shift the composition of microbes in the gut may be able to help treat disorders such as anxiety and depression
In a classic comic strip, most recently gracing the Beano, tiny characters called “numskulls” live in the head of a chap called Edd, controlling what he gets up to – often with hilarious results. It has run for decades, presumably because the idea that there could be critters within us capable of exerting a profound mental and physical influence seems pretty absurd.
But it appears science is having the last laugh: in recent years the idea has spawned myriad research papers – except that instead of minuscule people at work inside one’s head, it is microbes in the gut that appear to be pulling the strings.
How microbes in the gut influence the brain – and vice versa – is still being unpicked. Studies have revealed possible routes of communication that include the immune system, branches of the vagus nerve that run from the gut to the brain, and interaction with the nerves and synapses that control the function of the gastrointestinal tract. If the links could be understood, and harnessed, experts say the impact could be profound.
Scientists hope that by shifting the composition of microbes in the gut, either by administering particular microbes or helping beneficial microbes to thrive, they may be able to help treat disorders such as anxiety and depression – an approach known as psychobiotics.
“A large percentage of people who take medication or psychotherapy to treat mild or moderate [cases] don’t respond,” says Prof John Cryan of University College Cork, a key figure in the field, who is working on how modifying gut bacteria might be beneficial alongside other treatments.
This bold idea is bolstered by decades of research revealing what has been dubbed the “microbiota gut-brain axis”.
Many experiments have involved taking germ-free mice – animals raised in a sterile environment with no microbes – and introducing “good” bacteria to their insides, resulting in a reduction in stress, anxiety and depression.
But while the results are exciting, there is a complication. “Mouse and human microbiota are hugely different,” says Bhismadev Chakrabarti, professor of neuroscience and mental health at the University of Reading.
Yet evidence is growing that our own gut microbes may exert a powerful influence on our brains. Early small studies, some industry funded, found that consumption of probiotics – good bacteria such as bifidobacteria and lactobacilli – might reduce psychological distress and even affect brain activity in regions involved in controlling the processing of emotion and sensation.
One study found that taking a probiotic was associated with a reduction in negative mood. Another found that administering Bifidobacterium longum to patients with irritable bowel syndrome reduced depression, while 2022 research found that gut microbes are associated with levels of depressive symptoms.
There is even evidence that gut microbes affect neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS): one study found mice with a similar disease deteriorate faster if they do not have a gut microbiome, while introducing the bacterium Akkermansia muciniphila appeared to have a beneficial effect on their behaviour and neurological motor abilities by increasing levels of vitamin B3. Intriguingly, low levels of vitamin B3 have been found in human ALS patients, and clinical trials involving B3 supplements are being planned.
For Cryan, the concept that microbes could play a key role in psychological and neurological conditions is not a surprise. “There has never been a time where the brain has existed without microbial signals. We have evolved with these friends, and they are friends with benefits,” he says.
Questions remain about which microbes might influence which disorders, and whether it is the microbes themselves, or the chemicals they produce, that are affecting the brain.
And as Cryan notes, multiple chemicals may be at play – while their influence might shift over time. “What might be playing a bigger role in early life may play less of a role in adults,” he says.
In addition, scientists are still trying to understand what is cause and what is effect. “People with depression may change their eating habits,” says Dr Philip Burnet, a neuroscientist in the department of psychiatry at the University of Oxford. “They may not even eat much at all if they’re severely depressed. So you don’t know what that’s doing to the gut anyway.”
There are also big variations in the gut microbiomes between individuals, thanks to differences in diet, the internal environment – for example inflammation, alterations in the mucus layer, or levels of various chemicals – and genetics.
Cryan says that has a flipside: “We might be able to get tailored treatments for people to manage their own mental health,” he says.
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