Why Is the Gut Called the “Second Brain”? What We Know—and Don’t Yet Know—About the Gut–Brain Connection (the gut–brain axis)

Does your stomach hurt before an important meeting? Does your bowel routine change when you travel? Many people have probably experienced something like this.

When explaining this connection between “feelings” and the “gut,” people often use the phrase “the gut is the second brain.” But I feel that the phrase has taken on a life of its own, giving rise to claims such as “the gut thinks” and “serotonin made in the gut can make you happy.”

In this article, you’ll learn three things:

• What the phrase “the gut is the second brain” refers to, and why it came about
• How the gut and brain communicate with each other (the gut-brain connection)
• What research has established, and what remains unknown

We’ll explain what is reported in research papers and by universities and research institutions.

“The second brain” means the gut has its own dedicated neural network

The phrase “the second brain” became widely known through The Second Brain, a 1998 book by Michael Gershon, a neuroscientist at Columbia University in the United States.

What Gershon called “the second brain” is the network of nerves spread throughout the gut wall. Its technical name is the enteric nervous system.

The gut has more than 100 million nerve cells

The enteric nervous system is thought to contain more than 100 million nerve cells. Gershon described this as “more than the spinal cord (the bundle of nerves that runs through the backbone)” (an article in Scientific American, 2010). Some publications give a range of “100 million to 600 million” (an article from Stanford University’s Wu Tsai Neurosciences Institute, 2023). The exact number varies between studies and has not yet been established.

The sheer number is surprising, but what matters is this:

The gut can carry out digestion on its own, without instructions from the brain

The enteric nervous system can regulate gut activity on its own, including movements that move food along (peristalsis), without waiting for instructions from the brain. Think of it as a “branch office” that can handle its daily work based on decisions made on site (the gut), without direction from headquarters (the brain).

Neuroscientists at Stanford University explain that even when a mouse’s gut is removed from its body and placed in a culture medium, it continues to move. That’s because the gut’s neural network can generate movement on its own, even when it is no longer connected to the brain.

However, it is not a place where thoughts are formed or decisions are made

This point is easy to misunderstand. Calling it “the second brain” does not mean that the gut thinks or makes decisions. An article in Scientific American also makes clear that the enteric nervous system is not a place for conscious thought or decision-making.

In other words, it’s best to understand “the second brain” not as “another mind,” but as “an independent neural system that can do its job without relying on the brain.”

The gut and brain are connected “bidirectionally” through several pathways

The fact that the gut has its own neural network is separate from the fact that the gut and brain communicate with each other. The exchange of information between the gut and brain, and their mutual influence, is called the “gut-brain connection” or “brain-gut connection.”

Brain to gut: the autonomic nervous system and hormones

Professor Shin Fukudo, a psychosomatic medicine specialist at Tohoku University, explains that the brain influences the gut through the autonomic nervous system (nerves that automatically regulate bodily functions; the sympathetic and parasympathetic nerves), the enteric nervous system, hormones, and other pathways (an interview article on nippon.com, 2022).

Just as tension can make your heart pound, stress perceived by the brain is also transmitted to the gut through the autonomic nervous system.

Gut to brain: the vagus nerve

The vagus nerve directly connects the brain and gut. According to Professor Fukudo, most signals carried by the vagus nerve travel not from the brain to the gut, but from the gut to the brain. You could say that the gut is constantly reporting to the brain, “This is what’s going on right now.”

The immune system and substances produced by gut bacteria

A review paper summarizes research on the gut-brain connection. Published in Physiological Reviews in 2019 by an Irish research group led by Cryan, it describes pathways connecting gut bacteria and the brain, including the vagus nerve and enteric nervous system, as well as the immune system and substances produced by gut bacteria (such as short-chain fatty acids).

Short-chain fatty acids are substances such as acetate and butyrate produced by gut bacteria. Research into how these substances are involved with the brain is ongoing.

In summary, the gut and brain are connected through several pathways—“nerves,” “hormones,” “the immune system,” and “substances produced by gut bacteria”—and the connection is bidirectional, not one-way. (This four-part classification is how we have organized the information in this article.)

Stomach pain when you’re nervous is a familiar example of the gut-brain connection

Familiar examples of the gut-brain connection include “getting a stomachache when you’re nervous” and “alternating between constipation and diarrhea when stressed.”

According to Professor Fukudo, irritable bowel syndrome (IBS) refers to a condition in which abdominal pain or changes in bowel habits persist despite tests finding no abnormality in the gut itself. Stress can be a trigger, and disruptions in the relationship between the brain and gut are thought to be involved. However, there is not always just one cause.

A health column by Yakult Central Institute, a corporate research institute, explains that IBS can involve a “vicious cycle”: signals of anxiety or stress from the brain reach the gut, causing it to overreact, and that stimulation then travels back to the brain, increasing distress. Because the connection goes in both directions—gut to brain and brain to gut—it can become a vicious cycle.

If abdominal pain or changes in bowel habits persist, don’t assume on your own that they’re “caused by stress”; consult a medical professional. The gut-brain connection is discussed only after confirming that there is no underlying gut disease.

“90% of serotonin is made in the gut” is true—but it is considered separate from serotonin in the brain

You may have heard that “90% of the body’s serotonin is made in the gut.” Serotonin is sometimes called the “happiness hormone.” This claim is indeed supported by research papers.

The introduction to a paper published in Cell in 2015 by a research group at the California Institute of Technology states that “more than 90% of the body’s serotonin is synthesized in the gut.”

Serotonin from the gut does not simply travel to the brain

However, stopping there can lead to a misunderstanding. It is explained that serotonin made in the gut does not simply travel to the brain and determine your mood. The brain has a checkpoint-like mechanism called the blood-brain barrier, which selectively allows substances in the blood to pass through. Serotonin is thought to be unable to cross this barrier (an editorial in a Turkish gastroenterology journal, 2020).

The same editorial explains that the body has two separate serotonin systems: serotonin “made in the brain” and serotonin “made in the gut and elsewhere.”

So the claim that “making lots of serotonin in the gut can make you happy” goes beyond what research has established. The connection between the gut and brain is thought to be studied not as serotonin being transported directly, but through pathways such as the “nerves, hormones, immune system, and substances produced by gut bacteria” discussed in the previous section.

Research suggests that gut bacteria are involved in serotonin production in the gut

The 2015 paper mentioned earlier reported, in experiments using mice, that some bacteria living in the gut promote serotonin production in gut cells. Mice without gut bacteria (germ-free mice) reportedly had lower levels of serotonin in the gut.

This study showed that “gut bacteria participate in producing substances involved in gut function.” Keep in mind that it did not investigate people’s moods or mental states.

What research tells us about the relationship between gut bacteria and the brain

Research into the relationship between gut bacteria and the brain has advanced in recent years. Here are three examples: the first two are studies using mice, and the third is a review that summarizes the broader research.

Mice without gut bacteria had a stronger stress response (2004)

A Japanese research group led by Nobuyuki Sudo compared “germ-free mice,” which have no gut bacteria, with mice that have normal gut bacteria. When exposed to the stress of physical restraint, the germ-free mice showed a stronger release of stress hormones (ACTH and corticosterone). The researchers also reported that introducing a type of Bifidobacterium into the germ-free mice reduced this excessive response (The Journal of Physiology, 2004).

This study showed that “the colonization of gut bacteria after birth is involved in the development of the system that responds to stress.”

Information from the gut traveled via the liver and brain to regulate gut immunity (Keio University and others, 2020)

A research group led by Professor Takanori Kanai of the Keio University School of Medicine identified a mechanism in mice by which information from gut bacteria is transmitted to the brain via the liver. The information reaching the brain was used to regulate the number of immune cells (regulatory T cells) that suppress intestinal inflammation, through a vagal reflex (Nature, 2020). When the vagus nerve carrying signals from the liver to the brain was cut, the number of these immune cells fell, and the condition of mice with colitis worsened.

This study showed that gut bacteria, nerves, and the immune system are connected through an indirect pathway: “gut → liver → brain → gut.”

Multiple pathways are thought to connect gut bacteria and the brain (review, 2019)

The review by Cryan and colleagues mentioned earlier outlines how gut bacteria and the brain exchange information through the immune system, the metabolism of tryptophan (an amino acid used to make serotonin), the vagus nerve, the enteric nervous system, and substances produced by bacteria, such as short-chain fatty acids. It also notes that many of these findings come from animal studies, and that research involving humans is still underway.

What we still don’t know

After reading the research so far, it may be tempting to say, “If you improve your gut health, your mental health will improve too.” However, it is important to be clear that researchers themselves have not gone that far.

Causal relationships in humans have not yet been established

Most of the studies introduced here report findings in mice. What happens in mice does not necessarily apply to people in the same way. Cryan and colleagues’ review also says that research involving humans remains a future challenge.

We can’t say that “eating something will change your mood”

The claim that “taking a specific bacterium or eating a particular food will improve your mood or mental state” has not been established in humans. Research into the gut-brain connection is still underway, and there is no answer yet to what you should consume, in what amounts, or what effects it might have.

Reading this article and concluding that “gut health practices can improve mental health problems” would go beyond what the research says. If low mood or anxiety persists, consult a medical professional before trying to address it through dietary changes.

Frequently asked questions

Q. Does the “second brain” really think?

No. The enteric nervous system is an independent neural system that can manage digestive movements and other functions without relying on the brain, but it is not a place where thoughts are formed or decisions are made. “The second brain” is a name that emphasizes this independence.

Q. Will improving my gut health make me feel better?

The research is still at an early stage. Experiments in mice have reported a relationship between gut bacteria and stress responses, but no effect along the lines of “eat this and you’ll feel better” has been confirmed in humans. It may be helpful to think of gut health practices as a way to start paying attention to your digestive health and reviewing your diet.

Q. My stomach hurts when I’m nervous. What should I do?

Temporary stomach pain when you’re nervous is considered a familiar example of the gut-brain connection, in which the brain and gut influence each other. However, if pain or changes in bowel habits persist or interfere with daily life, it is important to check for an underlying gut condition. Don’t diagnose yourself; consult a medical professional.

Summary

The three key points of this article are:

• “The gut is the second brain” refers to the fact that the gut wall has its own neural network (the enteric nervous system), made up of an estimated 100 million to several hundred million nerve cells, which can regulate gut activity without instructions from the brain. It is not a place where thoughts are formed or decisions are made.
• The gut and brain are connected in both directions through several pathways: nerves (such as the vagus nerve), hormones, the immune system, and substances produced by gut bacteria. “Getting a stomachache when you’re nervous” is a familiar example.
• Research in mice has reported a relationship between gut bacteria and stress responses, but causal relationships in humans and whether particular foods can change your mood remain unknown.

One thing you can do starting today is to jot down how you’re feeling or what happened that day whenever you notice your digestive health. You may begin to see the connection between your “feelings” and your “gut” a little more clearly.

You may also find these related articles helpful.

• What is gut flora? A simple guide to “good,” “bad,” and “opportunistic” bacteria
• What are probiotics? A look at the bacteria found in yogurt, natto, and nukazuke pickles

Why not add kestose to your daily gut health routine?

The information above introduces research on the gut-brain connection. It does not demonstrate the effects of kestose.

Kestose is an oligosaccharide that serves as food for beneficial bacteria. Nakaya Shoten’s product is made with 100% kestose, the smallest oligosaccharide unit composed of three sugars. Each box contains 30 sachets of 3 g. Take one sachet per day as a guide, adding it to yogurt or a drink. It has a mildly sweet taste. If you’re interested in your gut microbiome, please consider it as one way to get started.

• Kestose, 3 g × 30 sachets (one-time purchase)
• Kestose, 3 g × 30 sachets (subscription)

For details such as pricing, please see the product page.

References

• Gershon MD. “The Second Brain.” HarperCollins (1998)
• Scientific American, “Think Twice: How the Gut’s ‘Second Brain’ Influences Mood and Well-Being” (2010; interview with Michael Gershon) https://www.scientificamerican.com/article/gut-second-brain/
• Stanford University Wu Tsai Neurosciences Institute, “Your gut - the second brain?” (2023) https://neuroscience.stanford.edu/node/1702
• nippon.com, “The Thinking ‘Gut’ and ‘Brain’: Their Mysterious Mechanisms” (2022; interview with Professor Shin Fukudo of Tohoku University) https://www.nippon.com/ja/japan-topics/c08004/
• Yakult Central Institute, Yakult Health Column, “The Brain-Gut Connection ③” https://institute.yakult.co.jp/feature/008/02.php
• Cryan JF, et al. “The Microbiota-Gut-Brain Axis.” Physiological Reviews 99(4):1877–2013 (2019) https://doi.org/10.1152/physrev.00018.2018
• Yano JM, et al. “Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis.” Cell 161(2):264–276 (2015) https://pmc.ncbi.nlm.nih.gov/articles/PMC4393509/
• Bektaş A, et al. “Does Serotonin in the intestines make you happy?” Turkish Journal of Gastroenterology 31(10):721–723 (2020) https://pmc.ncbi.nlm.nih.gov/articles/PMC7659911/
• Sudo N, et al. “Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice.” The Journal of Physiology 558(1):263–275 (2004) https://doi.org/10.1113/jphysiol.2004.063388
• Keio University, press release, “Mechanism revealed by which information from gut bacteria is integrated in the liver and transmitted to the brain, where a vagal reflex regulates the production of intestinal regulatory T cells” (June 12, 2020) https://www.keio.ac.jp/ja/press-release/20200612-3/

This article provides general information about diet. It is not intended to diagnose, treat, or prevent disease. If you have concerns about your health, have a chronic condition, or have persistent symptoms, please consult a doctor.