Butterflies in your stomach before a big presentation is a familiar experience, but surprisingly, scientists don’t yet know exactly how this happens. The gut-brain axis – the brain’s influence on the gastrointestinal tract and the other way around – is now a subject of keen scientific interest.

A recent review, published in Neuropsychiatric Disease and Treatment, covered what we know so far about the gut-brain axis, and especially the role of the hundreds of trillions of microorganisms in the digestive tract. Authors report that people with certain brain-related conditions show an altered gut microbiota: those with depression and anxiety, autism spectrum disorder, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) have a microbiota that is somehow different from healthy people. But these associations, as interesting as they are, don’t necessarily mean the gut and the brain influence each other.

The key issue is whether changing the microbiota experimentally can change the brain, and vice versa. Authors of the review cite studies showing that this can indeed be true for healthy people. In one study, for example, healthy women consumed a fermented milk product with four probiotics and were then tested via functional magnetic resonance imaging; researchers found differences in the activity of brain regions that control emotion and sensation. Another study found that healthy volunteers consuming a probiotic formulation decreased their scores on measures of psychological distress. Although not all studies show positive effects on the brain, evidence is growing that in healthy individuals the gut microbiota and the brain are in constant communication.

The next step is figuring out how the communication occurs. Are the gut microbiota and the brain communicating via nerves? Hormone signals? Facebook?

The gut-brain communication seems to rely on at least two things: neurons of the enteric nervous system (ENS) and the vagus nerve.

The gastrointestinal tract has its own nervous system, the ENS, which usually keeps the intestines running smoothly by moving food to the right place at the right time. Review authors cite evidence that the microbiota can have ‘electric’ effects on certain impulse-transmitting cells of the ENS. These neurons have reduced excitability in germ-free mice; when a healthy microbiota was restored in the mice, the excitability returned to normal. Not only that, but also feeding Lactobacillus reuteri to rodents increased these neurons’ potential to generate signals. It’s even possible that different kinds of bacteria influence the ENS neurons differently, with some tending to excite responses and some tending to dampen them.

Another important player in gut-brain communication is the vagus nerve, number 10 of 12 cranial nerves stretching outward from the brain and spinal cord. Messages seem to travel in both directions through the vagus nerve. In one experiment, giving Lactobacillus rhamnosus to mice reduced anxiety and depression behaviours, but not if the mice had surgical removal of a section of the vagus nerve.

Overall, microbiota-ENS communication influences the vagus nerve. Certain gut hormones and peptides might also spur the vagus nerve to communicate with the brain. Moreover, several other communication pathways are under investigation by scientists, including the neuroendocrine system (cells that produce and release hormones) and the immune system.

If the gut and the brain send messages back and forth all the time, could we change those messages by changing the microbiota? Would we then have the potential to unlock new treatments for brain-related disorders?

Limited research is available, say the authors, on how microbiota-modulating agents might affect the brain in clinical populations. There is some evidence, however, that probiotics and prebiotics can reduce depressive and anxiety symptoms in certain groups. One study found the probiotic Lactobacillus casei Shirota decreased anxiety in patients with chronic fatigue syndrome. Another study observed that a prebiotic reduced anxiety scores in a subgroup of patients with IBS. Probiotics have also shown some benefit in improving clinical outcomes of porto-systemic encephalopathy, a neuropsychiatric syndrome associated with liver and digestive dysfunction. In animal models, probiotics, prebiotics, antibiotics, and fecal microbiota transplantation have all shown potential to alter the gut microbiota and the way it communicates with the brain, but many more studies are needed in humans.

Without a doubt, the gut and the brain are keeping tabs on each other. The task facing scientists is to delve deeper into the molecular actions that allow this communication to take place, helping us understand the importance of the gut-brain axis in human health.