The mysteries of our “second brain” are a profound new frontier in 21st century medical science. While research is rapidly discovering amazing connections between our gut and our brain, little is known about how these two distinct parts of the body communicate with each other. A remarkable new study has upturned existing ideas surrounding gut-brain communication, revealing a fast-acting neural circuit allowing gut cells to communicate with the brain in just seconds.
We know several areas in the brain manage feelings of hunger and energy expenditure. The generally accepted hypothesis is that sensory cells in the gut emit certain hormones that interact with parts of the brain letting us know, for example, when we have eaten too much.
But unlike other senses that are communicated with the brain, such as sight or touch, this gut-brain communication process is frustratingly indirect… and slow. The communication delay has increasingly become a source of frustration as more and more research is revealing dramatic connectionsbetween our gut and our brain.
Remarkable new work from a team of researchers at Duke University has now revealed a previously unknown direct circuit between the gut and the brain that could allow for fast sensory communication that doesn’t relay on laborious hormonal signalling.
The research began with a big discovery in 2015 revealing that enteroendocrine cells, the cells in our gut thought to be the primary sensory receptor that communicate with the brain, actually contained nerve endings that seemed like they could directly synaptically communicate with vagal neurons and subsequently, the brain.
The new study first revealed that direct, and near instant, communication occurred between the gut and brain. A mouse was administered with a rabies virus that had been engineered with a green fluorescent tag. Tracing the signal of communication as the gut informed the brain of this virus revealed an immediate response in the vagus nerve. In under 100 milliseconds a single signal was seen to travel from the gut to the brainstem.
In order to understand this new neural circuit, the team grew enteroendocrine cells in a lab dish alongside vagal nerve neurons. Not only did these two elements rapidly demonstrate communication, but it was discovered that glutamate, a foundational neurotransmitter, modulated the rate of transmission. What this experiment impressively revealed was that enteroendocrine cells don’t solely signal to the brain via hormonal triggers, but also can directly communicate via neural synapses.
“Scientists talk about appetite in terms of minutes to hours. Here we are talking about seconds,” says Diego Bohórquez, senior author of the study. “That has profound implications for our understanding of appetite. Many of the appetite suppressants that have been developed target slow-acting hormones, not fast-acting synapses. And that’s probably why most of them have failed.”
Not only does this overturn many ideas around how appetite and satiety is communicated from the gut to the brain, but it reveals a fundamentally important new neural circuit. The authors of the new study even suggest an entirely new name for these gut cells seen to have synaptic communication with the vagus nerve. They are dubbed neuropod cells.
“We think these findings are going to be the biological basis of a new sense,” adds Bohórquez. “One that serves as the entry point for how the brain knows when the stomach is full of food and calories. It brings legitimacy to idea of the ‘gut feeling’ as a sixth sense.”