Gut communicates directly with brain

Green label shows that neurons connect directly with enteroendocrine cells (red) in laboratory cultures.Bohórquez lab, Science

The gut has long been known to communicate with the brain. The stomach and intestines can send information about hunger or feeling full, or about the presence of dangerous microbes. However, scientists thought that this communication only happened through hormones released into the bloodstream. Hormones move relatively slowly, taking minutes or longer to reach their targets.

Scientists have recently wondered if more direct connections exist between the gut and the brain. Several years ago, researchers led by Dr. Diego Bohórquez of Duke University found synapses in a rare type of gut cell. Synapses are the junctions between neurons (nerve cells) that pass chemical messengers called neurotransmitters.

Bohórquez and his colleagues wanted to better understand what these synapses in the gut were doing. They used mice to investigate how information moves from these gut cells, called enteroendocrine cells, to the brain. The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and Office of the Director (OD). Results were published on September 21, 2018, in Science.

The team first used a labeled version of the rabies virus to trace the neural circuit connected with enteroendocrine cells in mice. (Rabies usually spreads through the body’s neurons by way of the synapses.) They saw that the virus could spread directly from enteroendocrine cells in the gut to neurons in the vagus nerve, which stretches from the brain all the way to the intestines.

The researchers next grew vagal neurons in culture with enteroendocrine cells. Synapses formed between the cell types, and adding sugar caused the neurons to fire as they would when communicating a message. This communication wasn’t seen when sugar was added to vagal neurons alone, suggesting that the message originated from the enteroendocrine cells. The speed of communication between the gut cells and vagal neurons was between 60 to 800 milliseconds.

In follow-up experiments in mice, the researchers showed that enteroendocrine cells can detect the presence of sugar in the gut and transmit the signal to vagal neurons within milliseconds. Further work showed that the chemical glutamate is the neurotransmitter involved in passing the sensory information from gut to brain.

“Scientists talk about appetite in terms of minutes to hours. Here we are talking about seconds,” Bohórquez says. “That has profound implications for our understanding of appetite.” The researchers plan to do further experiments to understand how this system transmits specific information about the nutrient and caloric content of food.

—by Sharon Reynolds