The gut microbiome is a vast ecosystem of organisms such as bacteria, yeasts, fungi, viruses and protozoans that live in our digestive pipes, which collectively weigh up to 2kg (heavier than the average brain).
John Cryan was originally trained as a neuroscientist to focus on everything from the neck upwards. But eight years ago, an investigation into irritable bowel syndrome drew his gaze towards the gut. Like people with depression, those with IBS often report having experienced early-life trauma, so in 2009, Cryan and his colleagues set about traumatising rat pups by separating them from their mothers. They found that the microbiome of these animals in adulthood had decreased diversity, he says.
The gut microbiome is a vast ecosystem of organisms such as bacteria, yeasts, fungi, viruses and protozoans that live in our digestive pipes, which collectively weigh up to 2kg (heavier than the average brain). It is increasingly treated by scientists as an organ in its own right. Each gut contains about 100tn bacteria, many of which are vital, breaking down food and toxins, making vitamins and training our immune systems.
Cryan’s study didn’t attract much attention, but a few years later, Japanese scientists bred germ-free animals that grew up to have an elevated stress response. This alerted Cryan and his colleagues that they might be able to target the microbiome to alleviate some of the symptoms of stress, he says.
The hope is that it may one day be possible to diagnose some brain diseases and mental health problems by analysing gut bacteria, and to treat them – or at least augment the effects of drug treatments – with specific bacteria. Cryan and his colleague Ted Dinan call these mood-altering germs “psychobiotics”, and have co-written a book with the American science writer Scott C Anderson called The Psychobiotic Revolution.
The psychobiotics of the title are probiotics that some scientists believe may have a positive effect on the mind. Probiotics are bacteria associated with healthy gut flora – such as the Lactobacillus acidophilus and Bifidobacterium lactis we see advertised in “live” yoghurt. More diverse bacterial cocktails can also be bought as food supplements, but they’re expensive.
Over the past decade, research has suggested the gut microbiome might potentially be as complex and influential as our genes when it comes to our health and happiness. As well as being implicated in mental health issues, it’s also thought the gut microbiome may influence our athleticism, weight, immune function, inflammation, allergies, metabolism and appetite.
The past month alone has seen studies linking the gut microbiome with post-traumatic stress disorder (people with PTSD had lower than normal levels of three types of gut bacteria); fathoming its connection with autoimmune disease; finding that tea alters the gut microbiome in anti-obesogenic ways; showing that “ridiculously healthy” 90-year-olds have the gut microbiome of young adults; and how targeting mosquitos’ gut flora could help beat malaria by increasing the malaria-attacking bacteria in their guts. And last week, two groundbreaking studies provided evidence that gut biodiversity influences whether or not immunotherapy drugs shrink tumours in cancer patients.
One story that caught the public’s imagination during the summer implied that “poop doping” (AKA microbiome enhancement via faecal transplant; what has been delicately described as a “reverse enema”) could become the new blood doping for elite cyclists. Lauren Petersen, a research scientist at the Jackson Laboratory for Genomic Medicine in Connecticut, looked at the stool samples of 35 cyclists, comparing those of elite and amateur cyclists. So sure was she that she would benefit from having some of the bacteria found in the gut microbiome of elite cyclists that she doped herself with the faeces one had donated. An endurance mountain biker herself, she swears (but can’t prove scientifically) that this took her from feeling too weak to train to winning pro cycling races. However, when you consider that one gram of faeces is home to more bacteria than there are humans on Earth – and how little we understand about the vast majority of them, good and bad – this is definitely not recommended.
An understanding of the gut’s importance to our wellbeing now fuels a global probiotic market projected to grow to $64bn (£48bn) by 2023. This month in Washington DC, the microbiome is a headlining topic at the world’s largest international neuroscience conference, for its potential role in helping to diagnose and slow the progress of degenerative brain diseases such as Parkinson’s and Alzheimer’s.
The challenge lies in pinpointing the cause and effect of specific bacteria, and translating the results into treatments. This isn’t easy. Giulia Enders, who wrote the international bestseller Gut, says: “We can check the stool for typical pathogens that would cause diarrhoea or viruses, but we have no idea what all the seemingly normal bugs are doing. We don’t really know which bacteria does what in who, so it is a big experiment.”
It’s a long, expensive process to test each strain in isolation, so scientists have started with small-scale human studies. Cryan tested Lactobacillus rhamnosus, which had reduced stress in his mice, on 29 people and found no benefit when compared with a placebo. But when he gave 22 healthy men a strain called Bifidobacterium longum 1714 for four weeks, the subjects presented lower levels of anxiety and stress hormone than before, and made between two and five fewer mistakes in memory tests. It looks as though B longum 1714 could be a bona fide psychobiotic, although Cryan says larger-scale human studies are needed.
Philip WJ Burnet, associate professor at the psychiatry department at the University of Oxford, has had promising results testing the effects of prebiotics on mood. Prebiotics are complex carbohydrates that humans can’t digest, but that probiotic bacteria thrive on. Essentially, prebiotics “are dietary fibres that feed bacteria already in our gut,” he says. “I argued that instead of proliferating the growth of single species as in taking a probiotic, if you eat these fibres you grow lots of species of good bacteria, so you’re more likely to get a hit.”
A very small, short trial – three weeks and involving 45 healthy volunteers – tested a commercially sold prebiotic called Bimuno, and suggested this might have the potential to reduce anxiety. “When you give someone an antidepressant,” says Burnet, “before you see a change in their depression or anxiety, it changes some underlying psychological mechanisms. You’re more vigilant to the positive, for example, if you’re on an antidepressant or are happy.”
In his study, people without the supplement or in the placebo group paid more attention to negative imagery because, he says, “I think we’re naturally morbid … But those on Bimuno paid more attention to the positive.” He is cautious to point out, however, that when people take antidepressants, these early changes don’t necessarily lead to their depression and anxiety symptoms improving. He also stresses: “Prebiotics, or indeed any dietary supplements, are unlikely to replace the drugs used for the treatment of psychiatric illnesses. But they might be useful in helping medication work better in people who do not respond very well to them.”
Should the worried well be hitting the prebiotics? “More studies are needed to test if they are a quick fix for brain disorders per se,” he says. “But if someone is unwell or feeling down from a cold, because the bacteria modulate the immune system, a quick fix would be prebiotics.” People hate hearing it, he says, but supplements can’t replace a healthy, varied diet. Lentils, asparagus and jerusalem artichokes are examples of natural prebiotic sources. “But who wants to eat a bowl of jerusalem artichokes when you can just pour some prebiotic powder on your cornflakes or on top of your McDonald’s?”
This year, the health journalist Michael Mosley tested the sleep-enhancing effects of prebiotics for his documentary The Truth About Sleep, and Burnet oversaw the five-day experiment. At the start of the trial, Mosley spent 21% of his time in bed awake – by the end that had shrunk to 8%. Of all the strategies Mosley tested to treat his insomnia, he found prebiotics the most effective. Bimuno promptly sold out.