Understanding the gut-brain axis: 7 things to know

Have you ever found yourself thinking, “I don’t feel sick, exactly. I just don’t feel … right?”

If so, odds are that you’re correct — and it may have something to do with the gut-brain axis. This connection between your digestive tract and central nervous system allows your brain and gut to communicate with and influence each other constantly.

But how does it work? How would you know if yours is not functioning well? And, is there anything you can do to support the gut-brain axis?

We went to Xiling Shen, Ph.D., a gastrointestinal medical oncology researcher at UT MD Anderson who is studying the gut-brain axis. Here’s what he shared. 

What is the gut-brain axis?

The gut-brain axis is how the brain monitors what’s happening in the digestive tract.

The brain and spinal cord make up the central nervous system. The nerves that stretch down into the gut and other areas of the body make up the peripheral — or outlying — nervous system.

“But the gut-brain axis involves more than just the gut (the tube that stretches from the mouth to the anus),” Shen explains. “The peripheral nervous system reaches into every organ that’s involved with digestion, including the liver, gall bladder and pancreas.”  

What is the significance of the gut-brain axis?

Historically, it’s been easy for doctors to dismiss vague concerns like, “I’m not really sure what’s wrong. I just know I don’t feel well,” as imaginary. Now, scientists understand a bit more about how the brain and body interact, so they can recognize that some of these complaints are valid.

“The connection between the gut and the brain is considered so significant today that the gut is sometimes referred to as ‘the second brain,’” says Shen. “It might be more accurate to call it ‘the first brain,’ though, since even the simplest organisms have to eat and process their food. The gut had to evolve first, before the brain.”

So, can your gut status affect your mental health?

Absolutely. “The neurons in your gut actually make up the largest portion of the peripheral nervous system,” says Shen. “And, most of the serotonin your body makes is produced in the gut.”

Serotonin is a chemical that acts as a neurotransmitter in the brain and a hormone in the body. It carries messages between nerve cells and helps regulate our moods.

“What we are finding is that many people who’ve been diagnosed with clinical depression also have chronic gut problems,” Shen says. “The toxic protein clumps that are characteristic of several degenerative brain disorders — like Parkinson’s disease and mad cow disease — often show up in the gut before the brain, too. We can actually see the neurons there. So, these are real, physical connections.” 

How does the gut-brain axis work?

Scientists don’t have all the answers to that just yet. But we do know that the gut-brain axis is a two-way street. So, messages can travel in both directions.

• Afferent nerve signals travel up to the brain from the gut. “I think of them as cameras and microphones that let the brain know what’s going on down there,” says Shen.
• Efferent nerve signals travel down from the brain to the gut. “I think of these as loudspeakers that can override the gut’s normal function by issuing new orders,” Shen adds. 

What happens when the gut-brain axis malfunctions? Are there any symptoms?

There’s no one tell-tale sign. But here’s an example: The myelin sheath that protects your nerve cells is made up of fats that are regulated by metabolism. They act as an insulator to protect the electrical signals that travel back and forth. Those sheaths are constantly being recycled and replaced. But if you don’t have a healthy gut-brain axis, that recycling process could be disrupted.

“This may result in ‘leaky’ signals, so the neurons have to work extra hard to send them,” Shen explains. “If the neurons become exhausted, that could start a domino effect, and you’ll end up with other health problems, too. All of these things are connected.” 

How can I improve my gut-brain axis?

Metabolism depends on our digestive organs as well as the bacteria and microbes that live inside us. These are what actually consume our food and help us absorb the nutrients they contain.

“The gut-brain axis senses all of those elements, too,” notes Shen.

One way to support it is by eating more fiber and less sugar. That’s because fiber is harder to digest, so much of it arrives intact in the colon, where it provides food for the good bacteria that live there.

“All of the sugars get absorbed fast by the small intestine, so the good bacteria rely on fiber for their nourishment,” Shen explains. “If they can’t find any, they start digging into the lining of the large intestine to feed themselves. That can lead to leaky gut syndrome and a host of other problems.”

Fiber also helps with bowel regularity. The gut moves when it feels pressure. So, if there’s not enough volume to your food, you won’t feel that stimulus. This can result in constipation.

If the good bacteria die off due to a lack of food, it can also give the bad bacteria a chance to take over. So, the right diet can support the gut-brain axis by helping the good bacteria outcompete the bad. Our dietitians recommend filling two-thirds of your plate with vegetables, fruits, whole grains, beans, nuts and seeds. The remaining one-third can be lean animal protein or plant-based protein.

“This may result in ‘leaky’ signals, so the neurons have to work extra hard to send them,” Shen explains. “If the neurons become exhausted, that could start a domino effect, and you’ll end up with other health problems, too. All of these things are connected. 

Can you reset the gut-brain axis?

Not exactly. But several methods are available to help physicians improve it. These include:

• Probiotics to repopulate the gut with healthy bacteria
• Anti-inflammatories to calm the system down
• Neuromodulators, like beta blockers and Botox, to regulate nerve sensitivity
• Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapy that reduces inflammation

“Under severe disease conditions, a good diet has a limited impact,” Shen explains. “Sometimes, you need stronger interventions.” 

How does the gut-brain axis relate to cancer treatment?

Cachexia, or wasting syndrome, is a serious, sometimes irreversible condition that contributes to about a third of all cancer-related deaths. It causes the severe, involuntary loss of both fat and muscle, despite efforts to increase calorie intake. Until now, there has been no effective treatment.

But Shen and some of his colleagues are exploring ways to change that. A clinical trial featuring the new vagal block electroneuromodulation therapy Shen and his colleagues developed will be opening at UT MD Anderson in May 2026, under the leadership of GI medical oncologist Brandon Smaglo, M.D.

And Shen recently published a study in which LIPUS was used to reduce the inflammation that contributes to cachexia, alleviating some of its symptoms.  

“The vagus nerve regulates the parasympathetic nervous system, which calms you down when you get upset,” notes Shen. “We developed a wearable skin patch that’s applied to the right side of the neck, where the right vagus nerve is located. By blocking its hyperactivation, we were able to restore liver function, enhance patients’ appetite, and reduce systemic inflammation, all of which contribute to cachexia.” 

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