The way antidepressants and other emotion-focused medications work could be reconsidered, after a breakthrough in the understanding of how the gut communicates with the brain.
Flinders University research has uncovered major developments in understanding how the gut communicates with the brain by investigating the vagus nerve, a crucial pathway in the gut-brain axis, influencing fluid and food intake, heart rate, energy metabolism, respiration and gut motility.
The team, led by Professor Nick Spencer from Flinder’s College of Medicine and Public Health, believe that their findings could have an impact on the chemical composition and use of medications such as antidepressants.
“The gut-brain axis consists of complex bidirectional neural communication pathway between the brain and the gut, which links emotional and cognitive centres of the brain, and as part of the gut-brain axis, vagal sensory nerves relay a variety of signals from the gut to the brain that play an important role in mental health and wellbeing,” Professor Spencer said.
“The mechanisms by which vagal sensory nerve endings in the gut wall are activated has been a major mystery but remains of great interest to medical science and potential treatments for mental health and wellbeing.”
For example, serotonin is a major hormone and neurotransmitter in the body and has been shown to play a major role in a range of bodily functions, including mental health and depression, and the majority of serotonin in the body, around 95%, originates in the gut.
“The vast majority of serotonin is made in specialised cells, called enteroendocrine cells (EECs), within the gut wall but we still don’t understand how serotonin released from EECs activates the sensory nerve endings of the vagus nerve,” Professor Spencer said.
“It had once been proposed that EECs make physical synaptic connections with the sensory nerve endings of the vagus and use fast neurotransmitters to activate vagal sensory endings. However, the results of our new research uncover that any substances (including serotonin) released from EEC cells must communicate via a process of diffusion to the sensory nerve endings of the vagus nerve, that lie in colon.
“We found that the distances between individual EECs that contain serotonin and vagal afferent nerve endings were too far apart to occur via a mechanism that involved synaptic communication and fast neurotransmission, as was previously thought.
“This is a major discovery for our understanding of gut-brain communication which has profound implications for drug developments, treatments of anxiety and depression and other digestive problems such as irritable bowel symptom (IBS), all of which involve serotonin in some way.”
The researchers used an intricate method of anterograde neuronal tracing from the sensory nerve cell bodies of the vagus nerve, which lie just outside the brain, but send their long nerve projections (axons) all the way down to the small intestine and proximal part of the colon.
“The mean distances between vagal nerve endings and the nearest serotonin containing EECs were hundreds of times greater than known distances that underlie synaptic transmission in vertebrates. This rules out any possible mechanism of fast synaptic transmission,” Professor Spencer said.
“The absence of any close physical contacts between serotonin-containing EECs and vagal nerve endings in our studies leads to the inescapable conclusion that the mechanism by which serotonin activates the sensory nerve endings of the vagus nerve is by diffusion.
“Our understanding of how the gut communicates with the brain, via sensory nerves has been substantially improved based on the findings of this study, and we look forward to exploring this topic further.”