If you’ve ever felt butterflies in your stomach when you’re nervous, you’ve already experienced the gut–brain axis.
The gut–brain axis is the two-way connection between your gut and your brain. It helps shape how you feel pain. You can think of it like a highway—signals are always traveling back and forth. What happens in your brain can affect your gut, and what happens in your gut can affect how your brain responds.
Most of the time, you don’t notice this. Your gut is always moving and digesting, but those signals stay in the background and don’t cause discomfort. But sometimes, the brain starts to process those signals differently. Sensations that are usually quiet—like movement, pressure, or food passing through—can become easier to feel, and for some people, they can become painful.
All pain is felt in the brain, but signals from the gut can change how strong that pain feels and how distressing it becomes. This is what the gut–brain axis means: not just what’s happening in the gut, but how the gut and brain are constantly communicating and shaping what you feel.
Within this system is another layer researchers are still working to understand: the gut microbiome.
The gut microbiome: an emerging piece of the gut–brain axis
The gut microbiome is the community of bacteria living in your digestive system. As Dr. Lara Crock explains, “the gut microbiome is a really complex forest—probably more complicated than the Amazon rainforest.”
Researchers are beginning to study how it may be linked to pain. In one study led by Dr. Crock with Stanford’s Dr. Vivianne Tawfik as a co-author, people with complex regional pain syndrome (CRPS) had different gut bacteria compared to those without chronic pain. This suggests a connection between the gut and the nervous system—but it does not mean the microbiome is the cause of pain.
The relationship appears to go both ways. Changes in the gut can happen alongside chronic pain, not just before it. This raises an important question: does the gut affect pain, or does pain affect the gut?
“The gut microbiome is a really complex forest—probably more complicated than the Amazon rainforest.”
Your environment may also play a role. People living in the same household often have similar gut bacteria and sometimes similar pain patterns, suggesting that factors like diet, stress, and daily routines may shape both.
For patients, this means the microbiome is one part of a larger system. It may influence pain, but it is also shaped by what your body is going through. It’s not something you need to control on its own. Instead, it responds to the same things that support treatment—like regular routines, stress management, and overall health.
Why gut pain can happen even when tests are normal
The gut–pain axis helps explain a group of conditions called disorders of gut–brain interaction. These include irritable bowel syndrome (IBS), functional dyspepsia, and other types of ongoing gut pain where symptoms are real but tests often come back normal. To understand this, it helps to look at two different types of conditions.
In some digestive diseases—like Crohn’s disease or ulcerative colitis—there is visible inflammation or damage in the gut. Doctors can see these changes on scans, scopes, or lab tests.
In disorders of gut–brain interaction, those visible changes may not be there. Instead, the problem is in how the system is working—how the gut moves, senses, and communicates with the brain. This means symptoms can be very real, even if tests look normal.
Symptoms of gut pain—and why they can feel so intense
For many people, the most confusing part of gut pain is not just what they feel, but how strongly they feel it.
Patients often describe:
- Bloating that feels constant or unpredictable
- Cramping or sharp pain that comes and goes
- A sense of pressure or fullness, even without eating much
- Urgency or discomfort that disrupts daily routines
Sensations that are usually quiet, like the movement of food or gas, become noticeable. The brain essentially turns up the volume on signals that would normally stay in the background.
For many people, this is when symptoms become hard to ignore—especially when tests don’t provide clear answers. This is often when people begin seeking care. If you are living with ongoing stomach pain, the first step is getting evaluated to make sure there is not an underlying condition that needs specific treatment.
Step 1: Initial evaluation
For most patients, care starts with a primary care doctor or a gastroenterologist.
At this stage, the goal is to rule out structural causes of pain—conditions where there is visible inflammation, infection, or damage in the digestive tract.
This may include:
- Blood tests
- Stool tests
- Imaging (such as CT scans or ultrasounds)
- Procedures like an endoscopy or colonoscopy
If something is found, treatment is directed at that condition.
Step 2: Shifting the focus of evaluation
For many patients, tests come back normal even though the pain is still very real. At this point, the focus of care begins to change. Instead of looking for damage or disease, doctors start to look at how the system is working—how the gut moves, how it senses, and how it communicates with the brain.
This means asking a different kind of question: not just where is the pain coming from, but how is the pain being generated? In some cases, the pain is driven by the gut itself. In others, it reflects changes in how the nervous system is processing signals. Often, it is a combination of both.
Step 3: Referral to specialists
At this stage, patients may be referred to specialists who focus on gut–brain conditions, such as a health psychologist, GI psychiatrist, or pain physician—like Dr. Dany Lamothe (GI psychiatry) or Dr. Kristen MacKenzie (pain medicine).
Care may become more team-based, depending on your symptoms:
- Gastroenterologist — continues to guide diagnosis and rule out disease
- Pain physician — addresses nervous system sensitization and chronic pain patterns
- GI behavioral medicine specialist — helps retrain how the brain and gut communicate
- Nutrition expert — supports steady, sustainable eating patterns
What treatment actually looks like—and what improvement means
Treatment for gut–brain conditions does not focus on just one part of the body. It focuses on the system as a whole—how the gut, brain, and nervous system are working together.
Instead of trying to “fix” a single problem in the gut, treatment is aimed at calming the system, reducing sensitivity, and helping the body return to a more stable state.
As Dr. Lamothe explains, this often includes approaches that help retrain how the brain and gut communicate. This may involve GI behavioral medicine, where patients learn skills to reduce symptom intensity, improve daily function, and feel more in control of their symptoms.
Treatment may also include medications, but not always in the way you’d expect. Rather than targeting inflammation or damage, some medications are used to help regulate how the nervous system processes pain signals.
From a pain perspective, Dr. MacKenzie often focuses on reducing sensitization—helping the nervous system become less reactive over time. This can involve a combination of medical treatment, lifestyle adjustments, and support for the broader pain system.
Nutrition is also part of care, but the goal is not extreme restriction. In fact, overly limiting foods can sometimes make symptoms worse by increasing stress and making the system more sensitive. Instead, the focus is on building a steady, sustainable pattern of eating that supports the body.
Improvement does not always mean zero symptoms. It often means:
- Less intense or less frequent pain
- Fewer disruptions to daily life
- Getting back to the activities that you enjoy
- More confidence in managing symptoms
- A greater sense of control over the condition
Over time, many people find that as their system becomes less reactive, symptoms become more manageable. This process takes time, but it is a meaningful shift—from constantly reacting to symptoms to gradually retraining how the body responds.
What you can do to manage gut pain and symptoms
Treatment does not only happen in a clinic. There are also small, daily steps that can help support your gut–brain system over time.
Both Lamothe and MacKenzie emphasize that the goal is not to control every symptom, but to help the nervous system feel more stable and less reactive.
- Keeping regular routines—such as eating at similar times each day, maintaining a steady sleep schedule, and staying engaged in daily activities—can help the body feel more predictable and safe. When the system feels safer, it is less likely to amplify signals from the gut.
- Many people start avoiding foods or situations that seem to trigger symptoms. While this may help in the short term, over time it can increase sensitivity and create more stress around eating. A more gradual, supported approach is often more helpful.
- Stress also plays a role. This does not mean symptoms are “just stress,” but it does affect how the gut and brain communicate. Skills that help calm the nervous system—such as breathing exercises, relaxation techniques, or structured therapies—can reduce how intense symptoms feel.
- Staying connected to daily life matters. Avoiding activities or movement can reinforce the body’s sense that something is wrong. Gradually returning to normal routines, at a manageable pace, can help retrain the system over time.
These steps are not quick fixes. But alongside medical care, they can play a meaningful role in helping symptoms become more manageable and less disruptive.
How research on the gut microbiome and gut–brain axis is shaping the future of chronic pain care
Research is starting to look at pain in a new way. Instead of searching for one single cause, doctors are learning how different parts of the body work together—like the gut, the brain, and the environment.
This could lead to better ways to understand what is driving your symptoms, and more targeted treatments over time. It may also include new approaches, like therapies that focus on the gut microbiome, as part of a larger care plan.
For patients, the takeaway is simple: care is starting to focus on the whole system, not just one part of the body.
