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Groundbreaking Research Sheds Light On The Mysteries of the Gut-Brain Connection

Doctors look at scans in a clinical setting

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Key Takeaways

  • The gut and the brain are connected through the central nervous system.
  • A new study provides a "groundbreaking" look at how the gut and brain communicate.
  • Experts say understanding more about the gut-brain relationship could help improve mental health and well-being.


An ever-increasing body of research suggests that the brain affects gut health, and vice versa. The intricate workings of the gut-brain axis—basically the communication system between these two parts of the body—remain something of a mystery.

However, a new study has shed some light on how the enteric nervous system (aka the “second brain”) communicates with both the brain and spinal cord.

“The gut is the largest organ in the abdomen, yet the most poorly understood,” says study author Nick Spencer, PhD, a professor at Flinders University and chair of Optogenetics Australia.

If we wish to better understand how the gut and brain communicate it’s essential to develop new techniques to unravel the mechanisms that underlie gut-brain communication, which Spencer calls “a new frontier in science”.

The Gut-Brain Connection

Because the gut and the brain are connected through the central nervous system, they are closely linked. 

“The gut is mostly controlled by the parasympathetic nervous system, which is an autonomic nervous system and is highly connected to the brain,” says Julian Lagoy, MD, a psychiatrist with Mindpath Health. 

“We see this clinically since a lot of people who are depressed and anxious also complain of symptoms in their gut, such as diarrhea and nausea,” Dr. Lagoy adds.

Scientifically, the gut and the brain are both influenced by a similar neurotransmitter called serotonin, Dr Lagoy explains. “The first line medicine to treat anxiety and depression in the brain is called a selective serotonin reuptake inhibitor (SSRI), which increases serotonin in the neural synapses in the brain.”

We know there is more serotonin in the gut than in the brain, which explains why a lot of the psychiatric medications that alter serotonin in the brain also have side effects in the gut.

A Closer Look at the Study 

The recent study, published in the American Journal of Physiology, reveals a breakthrough discovery regarding how the specialized cells within the gut wall communicate with sensory nerve endings.

Researchers found that these cells, known as enterochromaffin (EC) cells, release serotonin—a chemical messenger that’s believed to act as a mood stabilizer—when stimulated by food, which then interacts with the nerves to communicate with the brain.

“Based on previous work from our lab, we suspected that sensory nerve endings in the gut wall that communicate with the brain do not make direct contact (synapses) with EC cells,” says Spencer. But while the findings were not a surprise, they weren’t consistent with previous studies that had extrapolated findings based on organ culture dishes.

Nick Spencer, PhD

If we better understand gut-brain communication and how EC cells release serotonin, we will have a better understanding of mechanisms that make us potentially feel good or bad.

— Nick Spencer, PhD

Almost all the serotonin in our bodies (around 95%) is made in the gut wall. “Serotonin plays a major role in how we feel and plays a major role in depression,” says Spencer. “If we better understand gut-brain communication and how EC cells release serotonin, we will have a better understanding of mechanisms that make us potentially feel good or bad.” 

Spencer and his team made the discovery using a neuronal tracing technique developed in their lab, which hasn’t been used anywhere else in the world. This enabled them to see the sensory nerve endings with clarity, for the first time, in the gut wall.

The authors say that because there is a direct connection between serotonin levels in our body and how we feel, understanding how the gut communicates with the brain is a priority.

What This Means For You

Mental health is complex and not necessarily solved the same way for all people. If you suffer from mental health issues, your first step is to seek advice from your doctor. 

However, it can be useful to keep up to date with studies into how the gut and brain communicate, and it's likely that this will remain a key area of research as doctors strive to identify how best to maintain a healthy mind and well-being.

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  1. Dodds KN, Travis L, Kyloh MA, Jones LA, Keating DJ, Spencer NJ. The gut-brain axis: Spatial relationship between spinal afferent nerves and 5-HT-containing enterochromaffin cells in mucosa of mouse colon. Am J Physiol Gastrointest Liver Physiol. 2022;322(5):G523-G533. doi:10.1152/ajpgi.00019.2022