Mind the Gut: A Q&A with Dr. Emeran Mayer

Jana K. Hoffman
Mahana Therapeutics
9 min readSep 25, 2020


Photo by Giles Mingasson

One of the more fascinating developments in modern medicine is the understanding of how deeply connected the gut and brain are to each other. The nerve cells in your gut — also known as the “little brain” — and your brain are constantly communicating back and forth. This has a significant impact on our digestive system, our bowel movements, our emotions and even how we cope with certain situations.

Brain-gut interactions are an especially important relationship to understand for those who have Irritable Bowel Syndrome (IBS). Thoughts, emotions and behaviors can affect gastrointestinal (GI) symptoms like constipation and diarrhea, as well as abdominal pain and bloating¹.

To further explore this relationship, I sat down with Emeran Mayer, MD, gastroenterologist, pioneer of brain-gut interactions research and one of Mahana Therapeutics’ advisors. Dr. Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA and the author of The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, And Our Overall Health.

The communication between our brain and our gut has changed the way scientists, researchers and physicians understand the connections between our mood, digestion and thoughts. What inspired you to explore these connections?

This has basically been my entire career. I can’t really explain to you, in retrospect, what started it 35 or 40 years ago. However, my interest in this area was one of the main reasons why I went into medical school. It became obvious to me from interacting with my patients that this was a very important and a very neglected component in medicine.

How does our gut communicate with our brain (and vice versa)?

Today, we know that there are several communication channels between cells in the gut that produce signalling molecules and areas within the brain that respond to these molecules. There are at least three systems that go from the gut to the brain.

Some are mediated by nerve pathways, mainly the sensory vagus nerve that responds to signals generated by cells in the gut — hormone-producing cells, muscle and nerve cells and microbes. These pathways send signals back into the brainstem and brain modulating emotion regulating networks. (Editor’s note: This is the part of the brain that controls your emotions.)

Another pathway involves hormonal-like signalling molecules, generated by certain cells in the gut, which go through the bloodstream to the brain and modulate the activity there.

The third pathway is mediated by gut-based immune cells. Forty percent of our entire immune system is located in the gut. These immune cells respond to things that go on inside the gut. Microbes activate immune cells, and immune cells produce cytokines, which then go through either the vagus nerve or the bloodstream into the brain.

And then we have the autonomic nervous system. These are the nerve pathways that go from the brain to the gut. They can modulate pretty much every gut function from contractions, transit, peristalsis (muscle contractions that occur in the digestive tract), secretion, blood flow, immune activity.

When you look at this, it’s really a circular communication system between gut and brain. The gut signals to the brain. The brain signals back to the gut. It’s a non-linear, complex network that modulates both gut functions and also our emotions.

Speaking of, why do we have “gut feelings” or get “butterflies” in our stomachs?

The brain sends a lot of nerve signals down into the gut. It affects, essentially, every aspect of gut function. Contractions are the most notable to us. We might hear gurgling or growling of the stomach. The same thing happens with secretions of the pancreas and gut [like mucus and water].

You could almost look at the gut as sort of a mirror image of our emotional state in the brain.

Every emotion, whether we feel it in the gut or not, will have a mirror image of it in the gut function. For people who are more sensitive than others, they feel these events going on in the gut all the time. They regularly experience these gut feelings. The butterflies are a well-known example. It’s basically related to the arousal of brain circuits both in positive and negative ways. Some people get these butterflies when they’re nervous, but others when they fall in love.

Our brain can also form a memory of these feelings over time. You can compare it to a library of tens of thousands of video clips that are encoded as you go through life’s emotional experiences. Later in life, as you make a decision, your brain can access this massive database, just like a Google search engine, and make a split-second “gut” decision.

How do different feelings trigger responses in the gut?

It’s been shown that emotions are accompanied by unique patterns of gut reactions. Each emotion also has its own GI (gastrointestinal) state to it. For example, with anger you get contractions of your stomach and of your sigmoid colon (“S” shaped portion of the large intestine). With anxiety, you get rapid transit through the stomach and small intestine and high-amplitude contractions in your sigmoid colon. With depression and sadness, you get a slowing down of the contractions. Many emotions are mixed in real life, such as anger and anxiety and depression and anxiety.

How do the ways we think or feel impact our bowel movements?

Depression is more often associated with constipation, resulting from the slowing down of peristalsis. Anxiety and fear are generally associated with diarrhea, consistent with these higher amplitude contractions. With anxiety, there’s an overstimulation of the autonomic nervous system from the stomach all the way down to the large intestine. This is the general framework of how the brain and gut interact and how it links emotional state to bowel habits.

How is COVID-19 affecting even those who typically have regular bowel movements?

That’s a good question. There’s a lot we don’t know about COVID-19. It’s certainly become clear that there’s a big psychological dimension to it for vulnerable people. We know, for example, an earthquake or an acute natural disaster has less of an effect on the brain-gut interaction than a chronic state of anxiety and worry has. In the case of COVID-19, the chronic uncertainty and worry about getting infected, in addition to the social isolation, are the biggest stress components.

Many people attribute IBS symptoms to their diets or certain foods. Why is IBS instead more commonly known as a disorder of the gut-brain interaction?

For me, it’s been an interesting development. Thirty years after we wrote articles about this concept — that IBS is a brain-gut disorder — and being laughed at in meetings and discredited by a majority of the field, all of a sudden it comes as this great insight. I’ve been in this business long enough now and have studied it and have seen thousands of patients in my career. I feel really confident that the basic concept that IBS is a disorder of brain gut interactions has not changed.

But even food has a big brain-gut component. I see this in many of my patients. For example, an executive working in downtown Los Angeles had to go out for lunch a lot. This person comes to me and says that he has food-related symptom triggers. In reality, it was the anticipatory anxiety of going to a restaurant where he didn’t know where the bathroom was that triggered GI symptoms. When he ate at home, he could eat anything without experiencing any GI symptoms.

And I’ve heard this over and over again about this anticipatory anxiety about what foods could trigger symptoms. It’s particularly bad, for example, for those who commute to work. Many of them don’t eat breakfast because they’re afraid they’re not going to make it to work without having to go to the bathroom. So they could say they avoid breakfast because breakfast triggers their symptoms. But, that’s not what it is. It’s the fear of having an uncontrollable bowel movement.

The brain-gut model, or now the brain-gut microbiome model, gives us an incredibly effective way to implement any brain- or mind-targeted therapies.

You can train your brain to be the normal player in the brain-gut interactions, rather than being the chronic disruptor.

How can people with IBS better regulate the connection between their brain and gut?

There’s a system within our brain called the salience network, which constantly monitors external things in the environment and internal things like sensations and signals from the body. It evaluates them in terms of “are they threatening the homeostasis of our body?” When they are perceived as threatening, a red light goes off. Then the brain responds with an autonomic response or pain response and does something to reestablish balance.

In IBS patients, that salience system is over-reactive. The alarm bells go off way too often. This is really where Cognitive Behavioral Therapy (CBT) comes in; to learn to normalize that salience assessment. Once that system is balanced, then all the downstream systems, like the emotional arousal and the sensory motor and the central autonomic network, all fall into place.

If you have lived for 30 years with the wrong warning system within your brain, you cannot fix it overnight. But, it can change fairly quickly. We see this with face-to-face CBT. When I talk to my colleague Jeff Lackner about their studies, he is convinced that even after three or four sessions, some people have significant symptom improvement. It’s like changing a dial on a computer. You don’t have to rebuild the whole computer.

What are the common ways IBS is treated today? How does it differ depending on what type of IBS you might have?

The treatment guidelines have gone through different phases in the last 35 years. Recommendations went from fiber and anxiety-lowering medications to an attempt by the industry to develop targeted brain-gut medications that affect the brain and the gut. Unfortunately, that ambitious approach failed.

Then the pharmaceutical industry decided that they’re just going to focus on the gut. These are basically motility and secretion modulating drugs to treat diarrhea and constipation. Often, symptom-related fears are reduced as a secondary effect if bowel function is normalized. However, if you come back to the fact that it’s a brain-gut disorder, there’s no real comprehensive IBS drug that would treat [all subtypes of] the disease.

Knowing what we now know about the gut-brain interaction, how can CBT treatments help reduce the severity of IBS symptoms?

When a patient undergoes CBT, you teach the patient to normalize the dysfunction of specific brain circuits. You’ll also see effects at the gut level in terms of bowel movement, frequency and even on the microbiome and metabolites. You treat both the brain and gut at the same time.

There’s clearly a space for combining medications with CBT. A reprogramming of circuits within the brain, the brain-gut axis and gut function can be assisted by medications. If someone had severe diarrhea, I would add an antidiarrheal initially in order to decrease the severe fear of being incontinent. On the other hand, if someone suffers from depression or anxiety, that patient may benefit from an adjuvant antidepressant, such as a SSRI (Selective Serotonin Reuptake Inhibitor).

What excites you about the future of gut-brain connection research? What don’t we know enough about this connection today?

I can’t wait to have an internet-based CBT. My prediction is that internet-based CBT, in combination with medications and lifestyle modifications, will become the future…baseline therapy. It would be a huge savings for the healthcare system.

From a science standpoint, I think there is a lot we will learn in terms of the brain-gut microbiome axis. In my second book, which I just submitted to the publisher, I talk a lot about neurodegenerative diseases like Alzheimer’s and Parkinson’s disease — to see how we can use our knowledge about the brain-gut microbiome axis to develop early diagnostic tools as well as therapeutic interventions. In the case of these neurodegenerative diseases, to be able to diagnose that early, like 30 years before the neurological symptoms start and to intervene preventively, would be a phenomenal breakthrough.

To learn more about Dr. Emeran Mayer, visit emeranmayer.com. We also invite you to watch a video snippet of our conversation about IBS.


¹The Brain-Gut Connection

The content in this article is not constituted as professional medical advice, diagnosis or treatment. Contact your general physician or other qualified health provider with questions you may have regarding a medical condition.



Jana K. Hoffman
Mahana Therapeutics

Writer and digital content strategist at Mahana Therapeutics.