A new study by researchers from several institutes including John B. Pierce Laboratory — which is formally affiliated with Yale — describes the mechanism by which the food we eat is communicated to the brain.

Led by Ivan de Araujo, a professor at the Icahn School of Medicine at Mount Sinai, the team found that there is a direct link between the gut and the reward regions of the brain, which are connected by the vagus nerve. The vagus nerve is comprised of a pair of the body’s longest cranial nerves that supply most of the body’s organs with nerves. The study was published in the journal Cell on Sept. 20.

“Gut-mediated sensations are strongly linked to motivational processes such as the pleasure and fullness produced by a meal,” said Wenfei Han, a professor at the Icahn School of Medicine at Mount Sinai and the first author of the paper. “A delicious candlelight dinner can possibly taste salty, sweet or spicy, or in some occasions, even poignant. However, what motivates us for the next reservation is the unforgettable feeling of satisfaction that ultimately arises from the gut.”

The research investigated how information travels from the gut to the dopamine-containing reward neurons in the brain, de Araujo said.

While previous research has shown that the vagus nerve helps the body decide when to finish eating, the study demonstrated that the nerve also emphasizes the consumption of specific pleasurable foods, said Guillaume de Lartigue, a professor at the University of Florida and one of the co-investigators. For example, he said, we find fatty food pleasurable because the vagal sensory neurons increase reward in response to fats.

Previously, it had been difficult to provide anatomical evidence for a gut-brain reward pathway because of the intertwined nature of the vagus nerve branches, according to Han.

Combining several techniques, the researchers were able to specifically target neurons from the upper gut of mice, said de Araujo.

According to de Araujo, the mice repeatedly stimulated their vagal neurons. This kind of self-stimulation, de Araujo said, is a hallmark characteristic of reward neurons.

Vagus nerve stimulators have been previously employed for treating depression, Han said, adding that this study elucidates the link between internal organs and the reward dopamine system.

“This may open more opportunities for efficient therapies and eventually benefit patients suffering from emotional and eating disorders,” she said.

De Araujo also noted that the hallmark characteristic of Parkinson’s disease is the death of dopamine neurons. A recent hypothesis on the disease proposes that Parkinson’s originates in the gut and travels through the central nervous system to affect the brain, instead of originating in the brain itself. This hypothesis comes from the fact that early symptoms of the disease’s development include constipation and gut dysfunction.

Although the research does not prove or disprove the model, de Araujo said, it provides an anatomical link between the gut and the dopamine neurons that die in Parkinson’s disease.

“Food preferences are not uniquely controlled by our taste buds: The gut has an important say in this too,” de Lartigue said. “Identifying the circuit responsible for making food pleasurable could be applied to alter our preferences and enable us to make healthier decisions.”

Eui Young Kimeuiyoung.kim@yale.edu 

Yale College Class of 2021; Yale Law School Class of 2025