More than 100 million neurons line the walls of the human gastrointestinal tract. This ‘second brain’ in the gut is known as the enteric nervous system and has an intimate relationship with the central nervous system as well as other body systems. We’ve all experienced that ‘gut feeling’ that drives us to make certain decisions, and we’ve all felt ‘butterflies in our stomach’ when we’re nervous. These are not just abstract ideas but real physiological phenomena mediated by complex signalling pathways between the gut and the central nervous system, called the gut-brain axis. One of the key pathways linking these two major organ systems involves signalling via the vagus nerve, the 10th and longest cranial nerve. Derived from the Latin word for ‘wandering’, it is suitably named as the nerve originates in the brainstem and ‘wanders’ all the way down to the abdominal organs, including the stomach and intestines. With a vast bodily distribution and a variety of functions, the vagus nerve is certainly one of the most important nerves in the body.
The vagus nerve transmits information between the gut and the brain and is the main nerve responsible for facilitating actions of the parasympathetic nervous system. These are the involuntary responses that promote ‘rest and digest’, working both with and against the sympathetic nervous system, which is responsible for stimulating the ‘fight or flight’ responses that are set off when we are exposed to stressful events. Sympathetic responses include increased heart rate and pupil dilation while parasympathetic responses include reduction in heart rate, pupil constriction, and peristalsis (waves of muscle contraction that propel food through the gut).
The enteric nervous system (ENS) in the gut is innervated by the vagus nerve, providing a means of gut-brain communication. Importantly, this information superhighway is bidirectional. Not only does the brain send signals to the neural network in the gut to control digestion but the ENS also sends information the other way. It’s becoming increasingly clear that nerve signals carried from the gut to the brain can influence our mood, decisions and well-being. In fact, vagus nerve stimulation, which involves sending electrical pulses along the vagus nerve, can be highly effective in patients with treatment-resistant depression.[1] We can see this ENS-CNS connection when we look at disorders of the bowel too. Cognitive behavioural therapy and certain antidepressants can be used to treat irritable bowel syndrome (IBS), with the aim to improve communication between the gut and the brain. Dr Jay Pasricha, director of the Johns Hopkins Centre for Neurogastroenterology, explains that “Our two brains ‘talk’ to each other, so therapies that help one may help the other. In a way, gastroenterologists (doctors who specialize in digestive conditions) are like counsellors looking for ways to soothe the second brain.”
From microbiome to mind
Amazingly, around 90 per cent of the signals passing along the vagus nerve originate not from the brain in your head but from the ‘second brain’ in your gut.[2] How can what happens in your gut affect your mental state? Growing evidence suggests that this bowel-to-brain communication may be mediated by the vast array of diverse microorganisms that make up what is called the gut microbiome.
Inhabiting the walls of your gut are billions of microorganisms, including bacteria, viruses, and other microbes. These ‘gut bugs’ do far more than just help to digest food. Research investigating the contribution of the gut microbiota in modulating the gut-brain axis indicates that gut bacteria can influence behaviour and mental health by signalling through the vagus nerve. Severing the vagus nerves of mice was shown to block the anxiety-reducing effects of the probiotic bacterium Lactobacillus rhamnosus, demonstrating the microbiota-vagus-brain signalling pathway in certain bacterial strains.[3] One way that gut microbiota might communicate with the brain and influence mood is by affecting levels of the neurotransmitter serotonin. Research at University College Cork indicates that certain gut bacteria such as Bifidobacteria produce the amino acid tryptophan, which is a precursor for the synthesis of serotonin.[4] Imbalances in serotonin levels in the brain have long been thought to play a role in depression and many widely prescribed antidepressants work by modulating serotonin levels. The group proposes that tryptophan metabolism might be a pathway through which the gut microbiome affects mood and potentially leads to psychiatric illnesses like depression. Another researcher in the field, microbiologist Jeroen Raes, said, “If you would have asked a neuroscientist 10 years ago whether they thought the gut microbiota could be linked to depression, many of them would have said you were crazy.” This research has led to massive interest in the development of ‘psychobiotics’, live bacteria which could potentially be used to improve mental health and treat mental illnesses.
Many other nervous system disorders have been linked to a malfunctioning gut. A novel theory suggests that Parkinson’s disease starts in the gut and spreads to the brain via the vagus nerve. A group from the University of Frankfurt found that the protein aggregation present in the brains of Parkinson’s patients is seen in the same types of neurons in the gut.[5] These findings give greater importance to a part of the body that seems an unlikely driver or contributor to neuropsychiatric disease at first glance. But although there has been an explosion of research into the gut-brain-axis over the past two decades, these ideas are not brand new. 2,500 years ago Hippocrates was thought to have said, “all disease begins in gut”. Only now we are beginning to understand the intimate relationship between the gut and the brain and draw links between diseases that are seemingly distinct. Uncovering the rich interactions between the brain above and the brain below will lead to a more wholesome understanding of the root causes of disease and illuminate the fascinating link between our microbiome and our mental health.
Author; Carissa Drake, MSc Pharmacology, New College.
References
[1] Corcoran C.D., Thomas P., Phillips J. & O’Keane V. Vagus nerve stimulation in chronic treatment-resistant depression: Preliminary findings of an open-label study. The British Journal of Psychiatry, 2006, 189(3), 282-283.
[2] Powley T.L. & Phillips R.J. I. Morphology and topography of vagal afferents innervating the GI tract. American Journal of Physiology Gastrointestinal Liver Physiology, 2002, 283, G1217–G1225.
[3] Bravo J.A., Forsythe P., Chew M.V., et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(38), 16050-16055.
[4] Bastiaanssen T.F.S., Cowan C.S.M., Claesson M.J., Dinan T.G. & Cryan J.F. Making sense of … the microbiome in psychiatry. International Journal of Neuropsychopharmacology, 2019, 22(1), 37-52.
[5] Kim S., Kwon S., Kam T., et al. Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease. Neuron, 2019, 103(4), 627-641.