Can microbes in our gut influence our emotions? That sounded farfetched ten years ago, but spectacular research in rodents has demonstrated that it is possible. Whether this works the same in humans as it does in mice is still an open question. Psychiatrist and neuroscientist Lukas Van Oudenhove investigates whether such an approach might be able to help people with emotional disorders.
It appears that the feeling of having butterflies or knots in your stomach when you are infatuated or stressed may soon have a scientific explanation. The fact that our emotions and gastrointestinal tract are connected does not seem particularly surprising. But how does it work? According to scientists, it is partly related to our gut flora: a varied collection of microorganisms – mostly bacteria – that populate our intestines.
These intestinal bacteria of course primarily serve to digest our food. During that process, they also produce various chemical substances, which are transmitted to the brain via the blood, but also influence other channels of communication between our gastrointestinal tract and brain. Intestinal flora may thus also influence our emotions and our behaviour. If intestinal bacteria influence our mental health, will we ever be able to treat people with emotional disorders, such as anxiety disorder or depression, through their intestines and their bacteria?
More than food
Professor Lukas Van Oudenhove directs LABGAS (Laboratory for Brain-Gut Axis Studies) in Leuven, an interdisciplinary team of neuroscientists, biomedical scientists, and psychologists. “Of course, we have long known that nutrients influence our brain. When you eat, your stomach and intestines start producing hormones. These hormones transmit a signal to your brain, indicating whether you are still hungry or not. But these substances also affect the reward system in your brain, making you feel satisfied or experience enjoyment. In other words, it is about much more than food intake.”
A lot of research on the brain-gut-axis has been conducted in rodents, with promising results, Van Oudenhove explains. Sterile mice – bred specially without intestinal bacteria – produce more stress hormone than mice with normal intestinal flora. If you give the sterile mice probiotics (healthy, living bacteria that is added to yoghurt, for example), their physical reactions become normal again. These results are inspiring, but they are unfortunately impossible to replicate in people. “We are born with intestinal flora that we inherit from our mother. And our physiology and psychobiology is completely different from that of mice.”
Nevertheless, certain interventions are possible in humans. For example, you can change intestinal flora with antibiotics, probiotics and prebiotics (food for the good bacteria). Or you can conduct a stool transplant. If you disrupt the intestinal flora in healthy mice by giving them antibiotics, it changes their emotional behaviour. When you transplant stool from anxious or depressed mice or even patients to healthy mice, the latter exhibit more anxious or depressed behaviour. “This obviously provides much food for thought, such as: can we treat people with anxiety symptoms with pro-, pre-, or antibiotics or through stool transplants?”
The press devoted considerable attention to these spectacular results. There is only one problem, Van Oudenhove tells us: “The majority of studies were conducted on laboratory animals. There is very little research on the applicability of these findings in human beings, and the studies that have been conducted had mixed results. The current hype is thus somewhat exaggerated. Instead of hit-and-miss experimentation, we must first research what works in humans and how.” This is now becoming the central focus of Van Oudenhove’s laboratory.
Good fatty acids
Among other things, Van Oudenhove’s research team researches the fatty acids in our intestinal tract. When we eat dietary fibres – which are primarily found in vegetables, fruit, legumes, grains, nuts, and seeds – certain bacteria in our large intestine ensure fermentation. This produces ‘short chain fatty acids’, such as butyric acid, acetic acid, and propionic acid. These fatty acids have beneficial effects in the gut: they are a source of energy for the intestinal cells, they dampen inflammation, and they help to combat cancerous cells.
But the short chain fatty acids not only have an effect in the gut, Van Oudenhove explains. “They are part of the communication between intestinal bacteria and the brain.” Lab research has shown that there is a link between short chain fatty acids and stress: “When we administer short chain fatty acids to people, in the form of capsules, we see that these people exhibit a lower hormonal response to psychological stress during experiments. The more short chain fatty acids there are in the blood, the less cortisol – the stress hormone. We must now conduct further research into how this works exactly and in whom it works best.”
Another area that Van Oudenhove will start researching is the role inflammation in microbiota-gut-brain communication. “When you research intestinal flora, you can divide people into four ‘enterotypes’, four categories of intestinal flora in which certain bacteria are dominant. Research conducted by my colleague Jeroen Raes has demonstrated that one enterotype is more associated with depression and lower emotional wellbeing. And we know that the same enterotype is also characterized by higher levels of inflammation in the body. But we only know that there is an association between the two, not what the causal relationships are.”
Van Oudenhove wants to research this further: “Does an inflammation make a difference with respect to stress and what happens precisely in the brain? We will give our test subjects a very low dose of a component of bacterial cell walls, but of course we do not make them seriously ill. They then have a mild transient inflammatory reaction and their immune system kicks in. We will test their stress response and monitor what happens in the brain. Given that short chain fatty acids mitigate inflammation, we also test whether they can reduce the stress response by dampening inflammation.”
Van Oudenhove mainly wants to conduct longitudinal research. This means that the test subjects are monitored over a longer period, and we take frequent measurements in order to map their development. These measurements include taking saliva to measure cortisol and blood to measure short chain fatty acids. In addition, the researchers conduct a stress test during which they scan the brain. A functional MRI scan shows which parts of the brain are active and a PET scan shows the chemical reactions in the brain, such as inflammation. “We have the great advantage in Leuven that we can conduct the two scans at the same time with one machine.”
We will thus have to wait some time for the results, but for the time being, we can all start eating more dietary fibre. Whether we will one day be discussing our diet with a psychologist or psychiatrist is still an open question. “The short chain fatty acids certainly have many positive effects, though the way they exert their influence on the brain is not entirely clear yet. I do not expect this to be a miracle cure for depression or anxiety, but hopefully it will evolve as a new weapon to combat them, to be combined with other treatments. When it comes to emotional disorders, there are of course many other factors in addition to your diet.” (if)